Andrea M. Brennan, Paul M. Coen, Theresa Mau, Megan Hetherington-Rauth, Frederico G. S. Toledo, Erin E. Kershaw, Peggy M. Cawthon, Philip A. Kramer, Sofhia V. Ramos, Anne B. Newman, Steven R. Cummings, Daniel E. Forman, Reichelle X. Yeo, Giovanna Distefano, Iva Miljkovic, Jamie N. Justice, Anthony J. A. Molina, Michael J. Jurczak, Lauren M. Sparks, Stephen B. Kritchevsky, Bret H. Goodpaster
Objective
The aim of this study was to examine associations of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.
Methods
Cross-sectional data from 829 adults ≥70 years of age were used. Abdominal, subcutaneous, and visceral AT and thigh muscle fat infiltration (MFI) were quantified by magnetic resonance imaging. SM mitochondrial energetics were characterized in vivo (31P-magnetic resonance spectroscopy; ATPmax) and ex vivo (high-resolution respirometry maximal oxidative phosphorylation [OXPHOS]). ActivPal was used to measure physical activity ([PA]; step count). Linear regression adjusted for covariates was applied, with sequential adjustment for BMI and PA.
Results
Independent of BMI, total abdominal AT (standardized [Std.] β = −0.21; R2 = 0.09) and visceral AT (Std. β = −0.16; R2 = 0.09) were associated with ATPmax (p < 0.01; n = 770) but not following adjustment for PA (p ≥ 0.05; n = 658). Visceral AT (Std. β = −0.16; R2 = 0.25) and thigh MFI (Std. β = −0.11; R2 = 0.24) were associated with carbohydrate-supported maximal OXPHOS independent of BMI and PA (p < 0.05; n = 609). Total abdominal AT (Std. β = −0.19; R2 = 0.24) and visceral AT (Std. β = −0.17; R2 = 0.24) were associated with fatty acid-supported maximal OXPHOS independent of BMI and PA (p < 0.05; n = 447).
Conclusions
Skeletal MFI and abdominal visceral, but not subcutaneous, AT are inversely associated with SM mitochondrial bioenergetics in older adults independent of BMI. Associations between ectopic AT and in vivo mitochondrial bioenergetics are attenuated by PA.
{"title":"Associations between regional adipose tissue distribution and skeletal muscle bioenergetics in older men and women","authors":"Andrea M. Brennan, Paul M. Coen, Theresa Mau, Megan Hetherington-Rauth, Frederico G. S. Toledo, Erin E. Kershaw, Peggy M. Cawthon, Philip A. Kramer, Sofhia V. Ramos, Anne B. Newman, Steven R. Cummings, Daniel E. Forman, Reichelle X. Yeo, Giovanna Distefano, Iva Miljkovic, Jamie N. Justice, Anthony J. A. Molina, Michael J. Jurczak, Lauren M. Sparks, Stephen B. Kritchevsky, Bret H. Goodpaster","doi":"10.1002/oby.24008","DOIUrl":"10.1002/oby.24008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to examine associations of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cross-sectional data from 829 adults ≥70 years of age were used. Abdominal, subcutaneous, and visceral AT and thigh muscle fat infiltration (MFI) were quantified by magnetic resonance imaging. SM mitochondrial energetics were characterized <i>in vivo</i> (<sup>31</sup>P-magnetic resonance spectroscopy; ATP<sub>max</sub>) and <i>ex vivo</i> (high-resolution respirometry maximal oxidative phosphorylation [OXPHOS]). ActivPal was used to measure physical activity ([PA]; step count). Linear regression adjusted for covariates was applied, with sequential adjustment for BMI and PA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Independent of BMI, total abdominal AT (standardized [Std.] <i>β</i> = −0.21; <i>R</i><sup>2</sup> = 0.09) and visceral AT (Std. <i>β</i> = −0.16; <i>R</i><sup>2</sup> = 0.09) were associated with ATP<sub>max</sub> (<i>p</i> < 0.01; <i>n</i> = 770) but not following adjustment for PA (<i>p</i> ≥ 0.05; <i>n</i> = 658). Visceral AT (Std. <i>β</i> = −0.16; <i>R</i><sup>2</sup> = 0.25) and thigh MFI (Std. <i>β</i> = −0.11; <i>R</i><sup>2</sup> = 0.24) were associated with carbohydrate-supported maximal OXPHOS independent of BMI and PA (<i>p</i> < 0.05; <i>n</i> = 609). Total abdominal AT (Std. <i>β</i> = −0.19; <i>R</i><sup>2</sup> = 0.24) and visceral AT (Std. <i>β</i> = −0.17; <i>R</i><sup>2</sup> = 0.24) were associated with fatty acid-supported maximal OXPHOS independent of BMI and PA (<i>p</i> < 0.05; <i>n</i> = 447).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Skeletal MFI and abdominal visceral, but not subcutaneous, AT are inversely associated with SM mitochondrial bioenergetics in older adults independent of BMI. Associations between ectopic AT and <i>in vivo</i> mitochondrial bioenergetics are attenuated by PA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 6","pages":"1125-1135"},"PeriodicalIF":6.9,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ciera L. Bartholomew, Catia Martins, Barbara Gower
Objective
The study objective was to assess the relationship between insulin sensitivity and changes in total lean mass (LM) and appendicular LM (ALM) during weight loss.
Methods
Individuals were randomly assigned to either a standard or a moderately reduced carbohydrate diet for 16 weeks. Body composition was assessed using dual-energy x-ray absorptiometry and insulin sensitivity index (SI) using an intravenous glucose tolerance test. Multiple linear regression was used to determine whether baseline SI was predictive of changes in total LM and ALM.
Results
Participants (n = 57; baseline BMI 32.1 ± 3.8 kg/m2) lost an average of 6.8 ± 3.2 kg of body weight (p < 0.001), with 1.5 ± 2.6 kg coming from LM (p < 0.05) and 0.5 ± 0.73 kg from ALM (p < 0.05). Multiple regression analysis demonstrated that SI was inversely associated with changes in total LM (kilograms; β = 0.481, p < 0.001), after adjusting for baseline LM, fat mass, acute insulin response to glucose, and weight loss. Similar results were seen when assessing ALM loss (β = 0.359, p < 0.05).
Conclusions
Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing LM loss.
研究目的研究目的是评估胰岛素敏感性与减肥期间总瘦肉量（LM）和阑尾瘦肉量（ALM）变化之间的关系：方法：研究人员被随机分配到标准或适度减少碳水化合物的饮食中，为期 16 周。使用双能 X 射线吸收测定法评估身体成分，使用静脉葡萄糖耐量试验评估胰岛素敏感性指数（SI）。采用多元线性回归法确定基线 SI 是否能预测总 LM 和 ALM 的变化：结果：参与者（n = 57；基线体重指数为 32.1 ± 3.8 kg/m2）平均减轻了 6.8 ± 3.2 kg 体重（p I 与总 LM（公斤；β = 0.481，p）的变化成反比：在采取减肥干预措施之前识别出胰岛素敏感性低的人群，可以采取个性化的方法，最大限度地减少胰岛素的损失。
{"title":"Association between insulin sensitivity and lean mass loss during weight loss","authors":"Ciera L. Bartholomew, Catia Martins, Barbara Gower","doi":"10.1002/oby.24022","DOIUrl":"10.1002/oby.24022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The study objective was to assess the relationship between insulin sensitivity and changes in total lean mass (LM) and appendicular LM (ALM) during weight loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Individuals were randomly assigned to either a standard or a moderately reduced carbohydrate diet for 16 weeks. Body composition was assessed using dual-energy x-ray absorptiometry and insulin sensitivity index (S<sub>I</sub>) using an intravenous glucose tolerance test. Multiple linear regression was used to determine whether baseline S<sub>I</sub> was predictive of changes in total LM and ALM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants (<i>n</i> = 57; baseline BMI 32.1 ± 3.8 kg/m<sup>2</sup>) lost an average of 6.8 ± 3.2 kg of body weight (<i>p</i> < 0.001), with 1.5 ± 2.6 kg coming from LM (<i>p</i> < 0.05) and 0.5 ± 0.73 kg from ALM (<i>p</i> < 0.05). Multiple regression analysis demonstrated that S<sub>I</sub> was inversely associated with changes in total LM (kilograms; β = 0.481, <i>p</i> < 0.001), after adjusting for baseline LM, fat mass, acute insulin response to glucose, and weight loss. Similar results were seen when assessing ALM loss (β = 0.359, <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing LM loss.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 6","pages":"1156-1162"},"PeriodicalIF":6.9,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mila S. Welling, Mostafa Mohseni, Renate E. H. Meeusen, Cornelis J. de Groot, Mariëtte R. Boon, Lotte Kleinendorst, Jenny A. Visser, Mieke M. van Haelst, Erica L. T. van den Akker, Elisabeth F. C. van Rossum
Objective
Considering limited evidence on diagnostics of genetic obesity in adults, we evaluated phenotypes of adults with genetic obesity. Additionally, we assessed the applicability of Endocrine Society (ES) recommendations for genetic testing in pediatric obesity.
Methods
We compared clinical features, including age of onset of obesity and appetite, between adults with non-syndromic monogenic obesity (MO), adults with syndromic obesity (SO), and adults with common obesity (CO) as control patients.
Results
A total of 79 adults with genetic obesity (32 with MO, 47 with SO) were compared with 186 control patients with CO. Median BMI was similar among the groups: 41.2, 39.5, and 38.7 kg/m2 for patients with MO, SO, and CO, respectively. Median age of onset of obesity was 3 (IQR: 1–6) years in patients with MO, 9 (IQR: 4–13) years in patients with SO, and 21 (IQR: 13–33) years in patients with CO (p < 0.001). Patients with genetic obesity more often reported increased appetite: 65.6%, 68.1%, and 33.9% in patients with MO, SO, and CO, respectively (p < 0.001). Intellectual deficit and autism spectrum disorder were more prevalent in patients with SO (53.2% and 21.3%) compared with those with MO (3.1% and 6.3%) and CO (both 0.0%). The ES recommendations were fulfilled in 56.3%, 29.8%, and 2.7% of patients with MO, SO, and CO, respectively (p < 0.001).
Conclusions
We found distinct phenotypes in adult genetic obesity. Additionally, we demonstrated low sensitivity for detecting genetic obesity in adults using pediatric ES recommendations, necessitating specific genetic testing recommendations in adult obesity care.
目的：考虑到成人遗传性肥胖诊断证据有限，我们对成人遗传性肥胖患者的表型进行了评估。此外，我们还评估了内分泌学会（ES）关于儿科肥胖症基因检测建议的适用性：我们比较了非综合征单基因肥胖症（MO）成人、综合征肥胖症（SO）成人和作为对照的普通肥胖症（CO）成人的临床特征，包括肥胖发病年龄和食欲：共有 79 名成人遗传性肥胖症患者（32 名 MO 患者，47 名 SO 患者）与 186 名普通肥胖症对照组患者进行了比较。各组患者的体重指数中位数相似：MO、SO 和 CO 患者的体重指数中位数分别为 41.2、39.5 和 38.7 kg/m2。MO患者的肥胖发病年龄中位数为3岁（IQR：1-6岁），SO患者为9岁（IQR：4-13岁），CO患者为21岁（IQR：13-33岁）：我们发现成人遗传性肥胖有不同的表型。此外，我们还发现，使用儿科 ES 建议检测成人遗传性肥胖的灵敏度较低，因此有必要在成人肥胖症护理中提供特定的基因检测建议。
{"title":"Clinical phenotypes of adults with monogenic and syndromic genetic obesity","authors":"Mila S. Welling, Mostafa Mohseni, Renate E. H. Meeusen, Cornelis J. de Groot, Mariëtte R. Boon, Lotte Kleinendorst, Jenny A. Visser, Mieke M. van Haelst, Erica L. T. van den Akker, Elisabeth F. C. van Rossum","doi":"10.1002/oby.24047","DOIUrl":"10.1002/oby.24047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Considering limited evidence on diagnostics of genetic obesity in adults, we evaluated phenotypes of adults with genetic obesity. Additionally, we assessed the applicability of Endocrine Society (ES) recommendations for genetic testing in pediatric obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared clinical features, including age of onset of obesity and appetite, between adults with non-syndromic monogenic obesity (MO), adults with syndromic obesity (SO), and adults with common obesity (CO) as control patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 79 adults with genetic obesity (32 with MO, 47 with SO) were compared with 186 control patients with CO. Median BMI was similar among the groups: 41.2, 39.5, and 38.7 kg/m<sup>2</sup> for patients with MO, SO, and CO, respectively. Median age of onset of obesity was 3 (IQR: 1–6) years in patients with MO, 9 (IQR: 4–13) years in patients with SO, and 21 (IQR: 13–33) years in patients with CO (<i>p</i> < 0.001). Patients with genetic obesity more often reported increased appetite: 65.6%, 68.1%, and 33.9% in patients with MO, SO, and CO, respectively (<i>p</i> < 0.001). Intellectual deficit and autism spectrum disorder were more prevalent in patients with SO (53.2% and 21.3%) compared with those with MO (3.1% and 6.3%) and CO (both 0.0%). The ES recommendations were fulfilled in 56.3%, 29.8%, and 2.7% of patients with MO, SO, and CO, respectively (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found distinct phenotypes in adult genetic obesity. Additionally, we demonstrated low sensitivity for detecting genetic obesity in adults using pediatric ES recommendations, necessitating specific genetic testing recommendations in adult obesity care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 7","pages":"1257-1267"},"PeriodicalIF":4.2,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyuan Wang, Xinyi Li, Yunsheng Wang, Zhongmei Ren, Xueqing Du, Jing Gao, Guangdong Ji, Zhenhui Liu
Objective
This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production.
Methods
Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment.
Results
Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells.
Conclusions
Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.
{"title":"Nkx1.2 deletion decreases fat production in zebrafish","authors":"Xinyuan Wang, Xinyi Li, Yunsheng Wang, Zhongmei Ren, Xueqing Du, Jing Gao, Guangdong Ji, Zhenhui Liu","doi":"10.1002/oby.24043","DOIUrl":"10.1002/oby.24043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate <i>nkx1.2</i> knockout zebrafish and <i>nkx1.2</i>-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of <i>nkx1.2</i> in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the <i>cebpa</i> promoter, thereby activating its transcription. Additionally, the expression of <i>nkx1.2</i> is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 7","pages":"1315-1328"},"PeriodicalIF":4.2,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ling Wang, Yandong Liu, Kai Li, Wenshuang Zhang, Yi Yuan, Kangkang Ma, Fengyun Zhou, Zitong Cheng, Jian Geng, Yongbin Su, Zhe Guo, Glen M. Blake, Xiaoguang Cheng, Yajun Liu, Klaus Engelke, Annegreet G. Vlug
Objective
We analyzed quantitative computed tomography (CT) and chemical shift–encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots.
Methods
In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2–L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements.
Results
Of the 168 men, 29% had normal BMI (<24.0 kg/m2), 47% had overweight (24.0–27.9 kg/m2), and 24% had obesity (≥ 28.0 kg/m2). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes.
Conclusions
Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.
目的：我们分析了来自中国队列的定量计算机断层扫描（CT）和化学位移编码磁共振成像（MRI）数据，以研究体重指数（BMI）和衰老对不同脂肪组织（AT）储藏的影响：在 400 名年龄在 22 至 83 岁之间的健康社区居民中，我们使用核磁共振成像量化了腰椎（L2-L4）骨髓脂肪组织（BMAT）、腰大肌和竖脊肌以及肝脏的质子密度脂肪分数（PDFF）。在 L2-L3 层使用定量 CT 测量了腹部总 AT、内脏 AT（VAT）和皮下 AT（SAT）面积。采用偏相关分析来评估各AT变量与年龄和体重指数的关系。在进行多元线性回归分析时，每个AT变量作为年龄和其他五个独立AT测量值的函数依次进行评估：结果：在 168 名男性中，29% 的人体重指数正常（2），47% 的人超重（24.0-27.9 kg/m2），24% 的人肥胖（≥ 28.0 kg/m2）。在 232 名女性中，这一比例分别为 46%、32% 和 22%。在男性和女性中，总 AT、VAT 和 SAT 均与体重指数有很强或非常强的相关性。在女性中，BMAT 和 ES PDFF 与年龄密切相关，而在男性中则呈中度相关。在男女两性中，BMAT PDFF 只与年龄相关，而与任何其他 AT 脂肪库无关。腰肌 PDFF 仅与 ES PDFF 相关，而与年龄或其他 AT 脂质无关。在男性中，肝脏 PDFF 与体重指数（BMI）和腹部脂肪含量（VAT）相关，与腹部脂肪含量（SAT）关系不大。VAT和SAT在男女两性中都与年龄和其他因素相关：结论：年龄和体重指数都与肥胖有关，但它们的影响因脂肪变性类型的不同而不同。
{"title":"Age and BMI have different effects on subcutaneous, visceral, liver, bone marrow, and muscle adiposity, as measured by CT and MRI","authors":"Ling Wang, Yandong Liu, Kai Li, Wenshuang Zhang, Yi Yuan, Kangkang Ma, Fengyun Zhou, Zitong Cheng, Jian Geng, Yongbin Su, Zhe Guo, Glen M. Blake, Xiaoguang Cheng, Yajun Liu, Klaus Engelke, Annegreet G. Vlug","doi":"10.1002/oby.24040","DOIUrl":"10.1002/oby.24040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We analyzed quantitative computed tomography (CT) and chemical shift–encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2–L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 168 men, 29% had normal BMI (<24.0 kg/m<sup>2</sup>), 47% had overweight (24.0–27.9 kg/m<sup>2</sup>), and 24% had obesity (≥ 28.0 kg/m<sup>2</sup>). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 7","pages":"1339-1348"},"PeriodicalIF":4.2,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaitlin H. Wade, Nicholas J. Timpson, Fergus W. Hamilton, Naveed Sattar, David Carslake, George Davey Smith
<p><b>TO THE EDITOR:</b> We read with interest the recent letter concerning our self-criticism [<span>(1)</span>] of the nonlinear Mendelian randomization (MR) methodology that we applied in an earlier publication in this journal [<span>(2)</span>]. In a constructive critique, the authors challenge the suitability of assigned sex as a negative control outcome under the definition that a valid negative control outcome should not be plausibly related to the exposure (here, body mass index [BMI]) and that these conditions can be tested within an analysis framework free of confounding and selection bias.</p><p>This is a reasonable point of consideration and one that justifiably cross-examines our use of the term “negative control.” However, this flags a more general issue—that our use of this term may not have been helpful from a formal point of view. Sadly, we fear that, again, the likely complications of nonlinear MR as described in our recent Perspective have been missed—that there are fundamental difficulties in the application of nonlinear MR analyses and that current methods (including the doubly ranked approach) are unable to avoid the generation of spurious associations.</p><p>We concede that the use of the UK Biobank as a population sample is potentially imperfect (mostly due to the biased, volunteer-based sampling frame) [<span>(3)</span>] for the deployment of a pure negative control analysis, as it will be for many other forms of both observational and applied epidemiological investigations. We have not provided an exhaustive simulation of the likely sources of possible bias to this extent, nor have we undertaken the same analysis in multiple independent studies (of different design) in efforts to quantify such flaws. However, what is important is that the analyses of both primary outcome and negative control (here, assigned sex) were undertaken in the same study and will suffer many of the same problems while remaining implausibly related; BMI may well be related to assigned sex, but BMI does not cause the latter. Importantly, the magnitude of selection bias within this sample and the specific question is unlikely to be large enough to explain these results, and, even if BMI was introducing the selection bias, this would influence the overall MR results as much as was seen using nonlinear methods and most likely not in a different and incomprehensible manner [<span>(4, 5)</span>].</p><p>There are a series of other potential arguments that would have been more well placed targeting our own use of the phrase negative control. For example, we may well expect a variable claimed to be an “instrument” for BMI that is derived from a polygenic risk score [<span>(4)</span>] to behave differently across strata of BMI (however formed), owing to the dimorphic characteristics of the underpinning genome-wide association study results. This is a potential biological flaw to the analysis and indeed one in which the differences in stratum-specific estima
{"title":"Response to “Importance of method assumptions”","authors":"Kaitlin H. Wade, Nicholas J. Timpson, Fergus W. Hamilton, Naveed Sattar, David Carslake, George Davey Smith","doi":"10.1002/oby.24056","DOIUrl":"10.1002/oby.24056","url":null,"abstract":"<p><b>TO THE EDITOR:</b> We read with interest the recent letter concerning our self-criticism [<span>(1)</span>] of the nonlinear Mendelian randomization (MR) methodology that we applied in an earlier publication in this journal [<span>(2)</span>]. In a constructive critique, the authors challenge the suitability of assigned sex as a negative control outcome under the definition that a valid negative control outcome should not be plausibly related to the exposure (here, body mass index [BMI]) and that these conditions can be tested within an analysis framework free of confounding and selection bias.</p><p>This is a reasonable point of consideration and one that justifiably cross-examines our use of the term “negative control.” However, this flags a more general issue—that our use of this term may not have been helpful from a formal point of view. Sadly, we fear that, again, the likely complications of nonlinear MR as described in our recent Perspective have been missed—that there are fundamental difficulties in the application of nonlinear MR analyses and that current methods (including the doubly ranked approach) are unable to avoid the generation of spurious associations.</p><p>We concede that the use of the UK Biobank as a population sample is potentially imperfect (mostly due to the biased, volunteer-based sampling frame) [<span>(3)</span>] for the deployment of a pure negative control analysis, as it will be for many other forms of both observational and applied epidemiological investigations. We have not provided an exhaustive simulation of the likely sources of possible bias to this extent, nor have we undertaken the same analysis in multiple independent studies (of different design) in efforts to quantify such flaws. However, what is important is that the analyses of both primary outcome and negative control (here, assigned sex) were undertaken in the same study and will suffer many of the same problems while remaining implausibly related; BMI may well be related to assigned sex, but BMI does not cause the latter. Importantly, the magnitude of selection bias within this sample and the specific question is unlikely to be large enough to explain these results, and, even if BMI was introducing the selection bias, this would influence the overall MR results as much as was seen using nonlinear methods and most likely not in a different and incomprehensible manner [<span>(4, 5)</span>].</p><p>There are a series of other potential arguments that would have been more well placed targeting our own use of the phrase negative control. For example, we may well expect a variable claimed to be an “instrument” for BMI that is derived from a polygenic risk score [<span>(4)</span>] to behave differently across strata of BMI (however formed), owing to the dimorphic characteristics of the underpinning genome-wide association study results. This is a potential biological flaw to the analysis and indeed one in which the differences in stratum-specific estima","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 8","pages":"1419-1420"},"PeriodicalIF":4.2,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Importance of method assumptions: Response to “Challenges in undertaking nonlinear Mendelian randomization”","authors":"C. Mary Schooling, Guoyi Yang","doi":"10.1002/oby.24055","DOIUrl":"10.1002/oby.24055","url":null,"abstract":"","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 8","pages":"1417-1418"},"PeriodicalIF":4.2,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Felona Gunawan, Brooke C. Matson, Anastasia Coppoli, Lihong Jiang, Yuyan Ding, Rachel Perry, Elizabeth Sanchez-Rangel, Renata Belfort DeAguiar, Kevin L. Behar, Douglas L. Rothman, Graeme F. Mason, Janice J. Hwang
Objective
Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism.
Methods
A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-13C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance.
Results
Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (Tmax/CMRglucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (VTCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and Tmax/CMRglucose (r = −0.477; p = 0.045).
Conclusions
We conclude that CMRglucose is unlikely to differ between groups due to similar VTCA, and, therefore, the glucose transport Tmax is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long-term brain function and health.
{"title":"Deficits in brain glucose transport among younger adults with obesity","authors":"Felona Gunawan, Brooke C. Matson, Anastasia Coppoli, Lihong Jiang, Yuyan Ding, Rachel Perry, Elizabeth Sanchez-Rangel, Renata Belfort DeAguiar, Kevin L. Behar, Douglas L. Rothman, Graeme F. Mason, Janice J. Hwang","doi":"10.1002/oby.24034","DOIUrl":"10.1002/oby.24034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Obesity is associated with alterations in eating behavior and neurocognitive function. In this study, we investigate the effect of obesity on brain energy utilization, including brain glucose transport and metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 11 lean participants and 7 young healthy participants with obesity (mean age, 27 years) underwent magnetic resonance spectroscopy scanning coupled with a hyperglycemic clamp (target, ~180 mg/dL) using [1-<sup>13</sup>C] glucose to measure brain glucose uptake and metabolism, as well as peripheral markers of insulin resistance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Individuals with obesity demonstrated an ~20% lower ratio of brain glucose uptake to cerebral glucose metabolic rate (T<sub>max</sub>/CMR<sub>glucose</sub>) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; <i>p</i> = 0.04). The cerebral tricarboxylic acid cycle flux (V<sub>TCA</sub>) was similar between the two groups (<i>p</i> = 0.64). There was a negative correlation between total nonesterified fatty acids and T<sub>max</sub>/CMR<sub>glucose</sub> (<i>r</i> = −0.477; <i>p</i> = 0.045).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude that CMR<sub>glucose</sub> is unlikely to differ between groups due to similar V<sub>TCA</sub>, and, therefore, the glucose transport T<sub>max</sub> is lower in individuals with obesity. These human findings suggest that obesity is associated with reduced cerebral glucose transport capacity even at a young age and in the absence of other cardiometabolic comorbidities, which may have implications for long-term brain function and health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 7","pages":"1329-1338"},"PeriodicalIF":4.2,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hila Zelicha, Alon Kaplan, Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Matthias Blüher, Nora Klöting, Uta Ceglarek, Berend Isermann, Michael Stumvoll, Yoash Chassidim, Ilan Shelef, Frank B. Hu, Iris Shai
Objective
The objective of this study was to explore the effects of a green Mediterranean (green-MED) diet, which is high in dietary polyphenols and green plant-based protein and low in red/processed meat, on cardiovascular disease and inflammation-related circulating proteins and their associations with cardiometabolic risk parameters.
Methods
In the 18-month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green-MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green-MED diet group also consumed green tea (3–4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat. Proteome panels were measured at three time points using Olink CVDII.
Results
At baseline, a dominant protein cluster was significantly related to higher phenotypic cardiometabolic risk parameters, with the strongest associations attributed to magnetic resonance imaging-assessed visceral adiposity (false discovery rate of 5%). Overall, after 6 months of intervention, both the MED and green-MED diets induced improvements in cardiovascular disease and proinflammatory risk proteins (p < 0.05, vs. healthy dietary guidelines), with the green-MED diet leading to more pronounced beneficial changes, largely driven by dominant proinflammatory proteins (IL-1 receptor antagonist protein, IL-16, IL-18, thrombospondin-2, leptin, prostasin, galectin-9, and fibroblast growth factor 21; adjusted for age, sex, and weight loss; p < 0.05). After 18 months, proteomics cluster changes presented the strongest correlations with visceral adiposity reduction.
Conclusions
Proteomics clusters may enhance our understanding of the favorable effect of a green-MED diet that is enriched with polyphenols and low in red/processed meat on visceral adiposity and cardiometabolic risk.
{"title":"Altered proteome profiles related to visceral adiposity may mediate the favorable effect of green Mediterranean diet: the DIRECT-PLUS trial","authors":"Hila Zelicha, Alon Kaplan, Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Matthias Blüher, Nora Klöting, Uta Ceglarek, Berend Isermann, Michael Stumvoll, Yoash Chassidim, Ilan Shelef, Frank B. Hu, Iris Shai","doi":"10.1002/oby.24036","DOIUrl":"10.1002/oby.24036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to explore the effects of a green Mediterranean (green-MED) diet, which is high in dietary polyphenols and green plant-based protein and low in red/processed meat, on cardiovascular disease and inflammation-related circulating proteins and their associations with cardiometabolic risk parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the 18-month weight loss trial Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT-PLUS), 294 participants with abdominal obesity were randomized to basic healthy dietary guidelines, Mediterranean (MED), or green-MED diets. Both isocaloric MED diet groups consumed walnuts (28 g/day), and the green-MED diet group also consumed green tea (3–4 cups/day) and green shakes (Mankai plant shake, 500 mL/day) and avoided red/processed meat. Proteome panels were measured at three time points using Olink CVDII.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, a dominant protein cluster was significantly related to higher phenotypic cardiometabolic risk parameters, with the strongest associations attributed to magnetic resonance imaging-assessed visceral adiposity (false discovery rate of 5%). Overall, after 6 months of intervention, both the MED and green-MED diets induced improvements in cardiovascular disease and proinflammatory risk proteins (<i>p</i> < 0.05, vs. healthy dietary guidelines), with the green-MED diet leading to more pronounced beneficial changes, largely driven by dominant proinflammatory proteins (IL-1 receptor antagonist protein, IL-16, IL-18, thrombospondin-2, leptin, prostasin, galectin-9, and fibroblast growth factor 21; adjusted for age, sex, and weight loss; <i>p</i> < 0.05). After 18 months, proteomics cluster changes presented the strongest correlations with visceral adiposity reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Proteomics clusters may enhance our understanding of the favorable effect of a green-MED diet that is enriched with polyphenols and low in red/processed meat on visceral adiposity and cardiometabolic risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 7","pages":"1245-1256"},"PeriodicalIF":4.2,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisa Doukbi, Patricia Ancel, Anne Dutour, Astrid Soghomonian, Shaista Ahmed, Victoria Castejon, Christelle Piperoglou, Vlad Gariboldi, Marien Lenoir, Eric Lechevallier, Bastien Gondran-Tellier, Romain Boissier, Mikael Ebbo, Frédéric Vély, Bénédicte Gaborit
<div> <section> <h3> Objective</h3> <p>Epicardial adipose tissue (EAT) is a visceral fat that has been associated with coronary artery disease and atrial fibrillation. Previous work has revealed that EAT exhibits beige features.</p> </section> <section> <h3> Methods</h3> <p>First, a new pan-genomic microarray analysis was performed on previously collected paired human EAT and thoracic subcutaneous AT (thSAT) from the EPICAR study (<i>n</i> = 31) to decipher a specific immune signature and its link with browning genes. Then, adaptive (T and B cells) and innate lymphoid cell (ILC1, ILC2, and ILC3) immunophenotyping assay panels, including CD127, CD117, and prostaglandin D2 receptor 2, were performed on prospectively collected paired human multiorgan donors (<i>n</i> = 18; INTERFACE study).</p> </section> <section> <h3> Results</h3> <p>In the EPICAR study, a positive correlation between the T helper cell subtype Th2 immune pathway and browning genes was found in EAT versus thSAT (<i>r</i> = 0.82; <i>p</i> < 0.0001). In the INTERFACE study, this correlation was also observed (<i>r</i> = 0.31; <i>p</i> = 0.017), and a preponderance of CD4<sup>+</sup>T cells, CD8<sup>+</sup>T cells, and a few B cells was observed in all ATs (<i>p</i> < 0.0001). An increase in ILCs was observed in visceral AT (VAT) (i.e., EAT + VAT; 30 ± 5 ILCs per gram of AT) compared with subcutaneous counterparts (i.e., thSAT + abdominal SAT; 8 ± 2 ILCs per gram of AT; <i>p</i> = 0.001), with ILC1 being the most frequent (ILC1 > ILC3 > ILC2). Numbers of ILCs per gram of AT correlated with several Th2 or browning genes (IL-13, TNF receptor superfamily member 9 [TNFRSF9], and alkaline phosphatase, biomineralization associated [ALPL]). Interestingly, a specific increase in EAT-ILC2 compared with other ATs was observed, including a significant proportion expressing CD69 and/or CD25 activation markers (97.9% ± 1.2%; <i>p</i> < 0.0001). Finally, more natural killer cells were observed in EAT + VAT than in thSAT + abdominal SAT (<i>p</i> = 0.01). Exclusion of patients with coronary artery disease in the EPICAR and INTERFACE studies did not modify the main findings. Gene expression phenotyping confirmed specific upregulation of Th2 pathway and browning genes (IL-33 and uncoupling protein 1 [UCP-1]) in EAT.</p> </section> <section> <h3> Conclusions</h3> <p>This is the first study, to our knowledge, to provide a comparison between innate and adaptive lymphoid cells in human EAT. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging.</p>
{"title":"Human epicardial fat has a beige profile and contains higher type 2 innate lymphoid cells than subcutaneous fat","authors":"Elisa Doukbi, Patricia Ancel, Anne Dutour, Astrid Soghomonian, Shaista Ahmed, Victoria Castejon, Christelle Piperoglou, Vlad Gariboldi, Marien Lenoir, Eric Lechevallier, Bastien Gondran-Tellier, Romain Boissier, Mikael Ebbo, Frédéric Vély, Bénédicte Gaborit","doi":"10.1002/oby.24023","DOIUrl":"10.1002/oby.24023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Epicardial adipose tissue (EAT) is a visceral fat that has been associated with coronary artery disease and atrial fibrillation. Previous work has revealed that EAT exhibits beige features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>First, a new pan-genomic microarray analysis was performed on previously collected paired human EAT and thoracic subcutaneous AT (thSAT) from the EPICAR study (<i>n</i> = 31) to decipher a specific immune signature and its link with browning genes. Then, adaptive (T and B cells) and innate lymphoid cell (ILC1, ILC2, and ILC3) immunophenotyping assay panels, including CD127, CD117, and prostaglandin D2 receptor 2, were performed on prospectively collected paired human multiorgan donors (<i>n</i> = 18; INTERFACE study).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the EPICAR study, a positive correlation between the T helper cell subtype Th2 immune pathway and browning genes was found in EAT versus thSAT (<i>r</i> = 0.82; <i>p</i> < 0.0001). In the INTERFACE study, this correlation was also observed (<i>r</i> = 0.31; <i>p</i> = 0.017), and a preponderance of CD4<sup>+</sup>T cells, CD8<sup>+</sup>T cells, and a few B cells was observed in all ATs (<i>p</i> < 0.0001). An increase in ILCs was observed in visceral AT (VAT) (i.e., EAT + VAT; 30 ± 5 ILCs per gram of AT) compared with subcutaneous counterparts (i.e., thSAT + abdominal SAT; 8 ± 2 ILCs per gram of AT; <i>p</i> = 0.001), with ILC1 being the most frequent (ILC1 > ILC3 > ILC2). Numbers of ILCs per gram of AT correlated with several Th2 or browning genes (IL-13, TNF receptor superfamily member 9 [TNFRSF9], and alkaline phosphatase, biomineralization associated [ALPL]). Interestingly, a specific increase in EAT-ILC2 compared with other ATs was observed, including a significant proportion expressing CD69 and/or CD25 activation markers (97.9% ± 1.2%; <i>p</i> < 0.0001). Finally, more natural killer cells were observed in EAT + VAT than in thSAT + abdominal SAT (<i>p</i> = 0.01). Exclusion of patients with coronary artery disease in the EPICAR and INTERFACE studies did not modify the main findings. Gene expression phenotyping confirmed specific upregulation of Th2 pathway and browning genes (IL-33 and uncoupling protein 1 [UCP-1]) in EAT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first study, to our knowledge, to provide a comparison between innate and adaptive lymphoid cells in human EAT. Further studies are ongoing to decipher whether these cells could be involved in EAT beiging.</p>\u0000 ","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 7","pages":"1302-1314"},"PeriodicalIF":4.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号