IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-05-28 DOI: 10.1002/oby.24008

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; ATP_max) 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 ATP_max (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.

研究目的本研究旨在探讨异位脂肪组织（AT）与老年人骨骼肌（SM）线粒体生物能的关系：方法：采用 829 名年龄≥70 岁的成年人的横断面数据。通过磁共振成像对腹部、皮下、内脏 AT 和大腿肌肉脂肪浸润（MFI）进行量化。对 SM 线粒体能量进行了体内（31P-磁共振波谱；ATPmax）和体外（高分辨率呼吸测定法最大氧化磷酸化[OXPHOS]）鉴定。ActivPal用于测量体力活动（[PA]；步数）。采用协变量线性回归，依次调整体重指数（BMI）和体力活动量（PA）：结果：与体重指数无关，总腹部 AT（标准化 [Std.] β = -0.21；R2 = 0.09）和内脏 AT（标准化 β = -0.16；R2 = 0.09）与 ATPmax 相关（p 2 = 0.25），大腿 MFI（标准化 β = -0.11；R2 = 0.24）与碳水化合物支持的最大 OXPHOS 无关（p 2 = 0.24），内脏 AT（Std. β = -0.17；R2 = 0.24）与脂肪酸支持的最大 OXPHOS 无关（p 结论：骨骼 MFI 和内脏 AT（Std：骨骼 MFI 和腹部内脏 AT（而非皮下 AT）与老年人 SM 线粒体生物能成反比，与体重指数无关。异位 AT 与体内线粒体生物能之间的关系因 PA 而减弱。

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引用次数: 0

Association between insulin sensitivity and lean mass loss during weight loss 减肥期间胰岛素敏感性与瘦体重下降之间的关系

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-05-28 DOI: 10.1002/oby.24022

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 (S_I) using an intravenous glucose tolerance test. Multiple linear regression was used to determine whether baseline S_I 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 S_I 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。

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引用次数: 0

Clinical phenotypes of adults with monogenic and syndromic genetic obesity 单基因和综合征遗传性肥胖成人的临床表型。

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-28 DOI: 10.1002/oby.24047

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。

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引用次数: 0

Nkx1.2 deletion decreases fat production in zebrafish Nkx1.2 基因缺失会降低斑马鱼的脂肪产量

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-26 DOI: 10.1002/oby.24043

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.

研究目的本研究旨在探讨具有 NK homeobox 结构域的转录因子 Nkx1-2 在调控脂肪生产中的作用：方法：采用定量实时聚合酶链反应或转录组测序分析基因表达。采用 CRISPR/Cas9 技术生成 nkx1.2 基因敲除斑马鱼和 nkx1.2 基因删除 3T3-L1 细胞。通过电泳迁移实验验证了 Nkx1-2 与启动子的结合：结果：Nkx1-2在斑马鱼脂肪生成的调控过程中起着关键作用。斑马鱼敲除 nkx1.2 会导致体重减轻，同时脂滴生成显著减少，内脏和肝脏脂肪含量降低。此外，与脂质生物合成有关的基因也明显下调。在 3T3-L1 前脂肪细胞中，Nkx1-2 通过与 cebpa 启动子结合，从而激活其转录，诱导分化为成熟脂肪细胞。此外，在 3T3-L1 细胞中，nkx1.2 的表达受 p38 MAPK、JNK 或 Smad2/3 信号通路的调控：我们的研究结果表明，Nkx1-2 是脂肪生成的正向调节因子，在脂肪细胞分化和脂质生物合成中发挥着关键作用。

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引用次数: 0

Age and BMI have different effects on subcutaneous, visceral, liver, bone marrow, and muscle adiposity, as measured by CT and MRI 通过 CT 和 MRI 测量，年龄和体重指数对皮下脂肪、内脏脂肪、肝脏脂肪、骨髓脂肪和肌肉脂肪有不同的影响。

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-23 DOI: 10.1002/oby.24040

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。

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引用次数: 0

Response to “Importance of method assumptions” 回应 "方法假设的重要性"。

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-21 DOI: 10.1002/oby.24056

Kaitlin H. Wade, Nicholas J. Timpson, Fergus W. Hamilton, Naveed Sattar, David Carslake, George Davey Smith

TO THE EDITOR: We read with interest the recent letter concerning our self-criticism [(1)] of the nonlinear Mendelian randomization (MR) methodology that we applied in an earlier publication in this journal [(2)]. 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.

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.

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) [(3)] 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 [(4, 5)].

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 [(4)] 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

致编辑：我们饶有兴趣地阅读了最近一封关于我们对本刊早前发表的一篇文章[(2)]中采用的非线性孟德尔随机（MR）方法进行自我批评的来信[(1)]。在建设性的批评意见中，作者对指定性别作为阴性对照结果的适宜性提出了质疑，其定义是：有效的阴性对照结果不应该与暴露（此处为体重指数[BMI]）有似是而非的关系，而且这些条件可以在没有混杂和选择偏差的分析框架内进行测试。然而，这也标志着一个更为普遍的问题--从形式上看，我们使用这一术语可能并无益处。遗憾的是，我们担心，我们在最近的《视角》中描述的非线性磁共振可能出现的并发症再次被忽视了--非线性磁共振分析的应用存在根本性的困难，目前的方法（包括双重排序法）无法避免产生虚假关联。我们承认，使用英国生物库作为人群样本可能并不完美（主要是由于以志愿者为基础的抽样框架存在偏差）[(3)]，无法进行纯阴性对照分析，正如许多其他形式的观察性流行病学调查和应用流行病学调查一样。我们并没有在这种程度上对可能的偏倚来源进行详尽的模拟，也没有在多个独立研究（不同的设计）中进行相同的分析，以量化这些缺陷。然而，重要的是，对主要结果和负面对照（此处为指定性别）的分析是在同一项研究中进行的，因此会出现许多相同的问题，同时仍然存在难以置信的关联；BMI 很可能与指定性别有关，但 BMI 并不导致指定性别。重要的是，该样本和具体问题中的选择偏差程度不太可能大到足以解释这些结果，而且，即使 BMI 带来了选择偏差，这也会像使用非线性方法一样影响 MR 的总体结果，而且很可能不会以不同的、难以理解的方式影响 MR 的总体结果[（4，5）]。例如，由于全基因组关联研究结果的二态性特征，我们完全可以预料到一个声称是体重指数 "工具 "的变量，在不同的体重指数分层（无论如何形成）中会有不同的表现[(4)]。这是分析的一个潜在生物学缺陷，实际上，工具和负对照之间的关系性质会导致特定分层估计值的差异。然而，即使是这种具有预期特性的情况，也不会产生说明性分析中产生的明显有缺陷的结果。至关重要的是，非线性 MR（即使有新的方法，但仍会产生值得怀疑的结果）[（1, 6）]的应用仍然不可靠，而且很可能受到一系列特征的影响，这些特征在不同的研究中会产生不同的影响（例如，暴露的遗传结构、感兴趣的结果、发现性遗传研究、暴露的分布以及暴露与结果之间的关系）。我们欢迎作者提出的总体观点，即需要使用三角测量来改善或至少说明在任何研究设计中遇到的推论困难。然而，我们仍然不相信，对分析或措辞的改进能够纠正我们在 2018 年的示例分析中指出的问题，或挽救试图进行非线性 MR 的现有方法。

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引用次数: 0

Importance of method assumptions: Response to “Challenges in undertaking nonlinear Mendelian randomization” 方法假设的重要性：回应 "进行非线性孟德尔随机化的挑战"。

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-21 DOI: 10.1002/oby.24055

C. Mary Schooling, Guoyi Yang

引用次数: 0

Deficits in brain glucose transport among younger adults with obesity 患有肥胖症的年轻成年人大脑葡萄糖转运功能存在缺陷。

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-19 DOI: 10.1002/oby.24034

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 (T_max/CMR_glucose) than lean participants (2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04). The cerebral tricarboxylic acid cycle flux (V_TCA) was similar between the two groups (p = 0.64). There was a negative correlation between total nonesterified fatty acids and T_max/CMR_glucose (r = −0.477; p = 0.045).

Conclusions

We conclude that CMR_glucose is unlikely to differ between groups due to similar V_TCA, and, therefore, the glucose transport T_max 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.

目的：肥胖症与饮食行为和神经认知功能的改变有关：肥胖与饮食行为和神经认知功能的改变有关。在这项研究中，我们探讨了肥胖对大脑能量利用的影响，包括大脑葡萄糖转运和代谢：共有 11 名瘦弱的参与者和 7 名肥胖的年轻健康参与者（平均年龄 27 岁）接受了磁共振波谱扫描和使用 [1-13C] 葡萄糖的高血糖钳夹（目标值约 180 毫克/分升），以测量脑葡萄糖摄取和代谢以及外周胰岛素抵抗标志物：结果：肥胖者的脑葡萄糖摄取与脑葡萄糖代谢率（Tmax/CMRglucose）之比（2.12 ± 0.51 vs. 2.67 ± 0.51; p = 0.04）比瘦者低约 20%。两组的大脑三羧酸循环通量（VTCA）相似（p = 0.64）。总非酯化脂肪酸与 Tmax/CMRglucose 之间呈负相关（r = -0.477；p = 0.045）：我们得出结论：由于 VTCA 相似，不同组间的 CMR 葡萄糖不太可能存在差异，因此肥胖症患者的葡萄糖转运 Tmax 较低。这些人类研究结果表明，肥胖与脑葡萄糖转运能力降低有关，即使肥胖者年龄较轻且没有其他心脏代谢合并症，这可能会对大脑的长期功能和健康产生影响。

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引用次数: 0

Altered proteome profiles related to visceral adiposity may mediate the favorable effect of green Mediterranean diet: the DIRECT-PLUS trial 与内脏脂肪相关的蛋白质组特征的改变可能会介导绿色地中海饮食的有利影响：DIRECT-PLUS 试验。

IF 4.2 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity

Pub Date : 2024-05-16 DOI: 10.1002/oby.24036

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.

研究目的本研究旨在探讨绿色地中海饮食（绿色-MED）对心血管疾病和炎症相关循环蛋白的影响，以及它们与心脏代谢风险参数的关系：在为期 18 个月的减肥试验 "膳食干预随机对照试验多酚未加工研究"（DIRECT-PLUS）中，294 名腹部肥胖的参与者被随机分配到基本健康膳食指南、地中海饮食（MED）或绿色-地中海饮食组。等热量地中海饮食组和绿色-地中海饮食组都食用核桃（28 克/天），绿色-地中海饮食组还食用绿茶（3-4 杯/天）和绿色奶昔（Mankai 植物奶昔，500 毫升/天），并避免食用红肉/加工肉类。使用 Olink CVDII 在三个时间点测量蛋白质组面板：结果：在基线时，优势蛋白质群与较高的表型心脏代谢风险参数显著相关，与磁共振成像评估的内脏脂肪率的关联性最强（误发现率为 5%）。总体而言，经过 6 个月的干预后，MED 和绿色-MED 饮食都能改善心血管疾病和促炎症风险蛋白（p 结论：MED 和绿色-MED 饮食都能改善心血管疾病和促炎症风险蛋白（p 结论：MED 和绿色-MED 饮食都能改善心血管疾病和促炎症风险蛋白（p 结论）：蛋白质组学集群可以帮助我们更好地了解富含多酚、低红肉/加工肉类的绿色-MED 饮食对内脏脂肪和心血管代谢风险的有利影响。

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引用次数: 0

Altered proteome profiles related to visceral adiposity may mediate the favorable effect of green Mediterranean diet: the DIRECT-PLUS trial. 与内脏脂肪相关的蛋白质组特征的改变可能会介导绿色地中海饮食的有利影响：DIRECT-PLUS 试验。

IF 6.9 2区医学 Q1 Nursing

Obesity

Pub Date : 2024-05-16 DOI: 10.1002/oby.24036

H. Zelicha, Alon Kaplan, A. Yaskolka Meir, E. Rinott, G. Tsaban, Matthias Blüher, Nora Klöting, U. Ceglarek, B. Isermann, Michael Stumvoll, Yoash Chassidim, Ilan Shelef, Frank B Hu, Iris Shai

OBJECTIVEThe 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.METHODSIn 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.RESULTSAt 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.CONCLUSIONSProteomics 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.

目的：本研究旨在探讨绿色地中海饮食（绿色-MED）对心血管疾病和炎症相关循环蛋白的影响，以及它们与心脏代谢风险参数的关系。方法在为期 18 个月的减肥试验 "膳食干预随机对照试验多酚未加工研究"（DIRECT-PLUS）中，294 名腹部肥胖的参与者被随机分配到基本健康膳食指南、地中海饮食（MED）或绿色-地中海饮食组。等热量地中海饮食组和绿色-地中海饮食组都食用核桃（28 克/天），绿色-地中海饮食组还食用绿茶（3-4 杯/天）和绿色奶昔（Mankai 植物奶昔，500 毫升/天），并避免食用红肉/加工肉类。结果在基线时，优势蛋白质群与较高的表型心脏代谢风险参数显著相关，其中与磁共振成像评估的内脏脂肪含量的关联性最强（假发现率为 5%）。总体而言，经过 6 个月的干预，MED 和绿色-MED 饮食都改善了心血管疾病和促炎症风险蛋白（p < 0.05，与健康饮食指南相比）。绿色-MED膳食带来了更明显的有益变化，主要由主要的促炎蛋白（IL-1受体拮抗蛋白、IL-16、IL-18、血栓蛋白-2、瘦素、前列腺素、galectin-9和成纤维细胞生长因子21；根据年龄、性别和体重减轻进行调整；p < 0.05）驱动。）18个月后，蛋白质组学聚类变化与内脏脂肪减少的相关性最强。结论蛋白质组学聚类可能会加深我们对富含多酚和低红肉/加工肉类的绿色-MED饮食对内脏脂肪和心脏代谢风险的有利影响的理解。

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