Luz M. Sánchez-Romero, Janine Sagaceta-Mejía, Jennifer S. Mindell, Álvaro Passi-Solar, Antonio Bernabé-Ortiz, Lizbeth Tolentino-Mayo, Alison Moody, Shaun Scholes
Objective
The objective of this study was to quantify changes over time in waist circumference (WC) relative to BMI by sex in the Americas (United States, Mexico, Chile, and Peru) and England.
Methods
Data from adults aged 25 to 64 years between 1997 and 2020 were analyzed, and US data were stratified by race and ethnicity groups. Sex-specific BMI and WC means and obesity and abdominal obesity prevalence were compared between the first and last surveys. Using data from all survey years, secular changes across the BMI and WC distributions were estimated, applying quantile regression models. BMI was added as a predictor of WC to estimate secular changes in WC relative to BMI. Interaction terms were included in all models to evaluate differences by sex.
Results
BMI and WC (except for Peru) showed larger secular increases at the upper-tails of the distributions in both sexes. Increases at the 50th and 75th WC percentiles relative to BMI were more pronounced in women than in men, with larger increases in US non-Hispanic White individuals and in England. In men, increases in WC independent of BMI were most evident in Mexico.
Conclusions
Disease risk associated with visceral fat is potentially underestimated by national surveillance efforts that quantify only secular changes in BMI.
{"title":"Sex differences in the secular change in waist circumference relative to BMI in five countries from 1997 to 2020","authors":"Luz M. Sánchez-Romero, Janine Sagaceta-Mejía, Jennifer S. Mindell, Álvaro Passi-Solar, Antonio Bernabé-Ortiz, Lizbeth Tolentino-Mayo, Alison Moody, Shaun Scholes","doi":"10.1002/oby.24110","DOIUrl":"10.1002/oby.24110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to quantify changes over time in waist circumference (WC) relative to BMI by sex in the Americas (United States, Mexico, Chile, and Peru) and England.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from adults aged 25 to 64 years between 1997 and 2020 were analyzed, and US data were stratified by race and ethnicity groups. Sex-specific BMI and WC means and obesity and abdominal obesity prevalence were compared between the first and last surveys. Using data from all survey years, secular changes across the BMI and WC distributions were estimated, applying quantile regression models. BMI was added as a predictor of WC to estimate secular changes in WC relative to BMI. Interaction terms were included in all models to evaluate differences by sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BMI and WC (except for Peru) showed larger secular increases at the upper-tails of the distributions in both sexes. Increases at the 50th and 75th WC percentiles relative to BMI were more pronounced in women than in men, with larger increases in US non-Hispanic White individuals and in England. In men, increases in WC independent of BMI were most evident in Mexico.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Disease risk associated with visceral fat is potentially underestimated by national surveillance efforts that quantify only secular changes in BMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1934-1947"},"PeriodicalIF":4.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309514","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}
Obesity is a chronic disease that affects more than 400 million adults with severe comorbidities. The search for new treatments to reduce its negative consequences is necessary. Orexins are hypothalamic neuropeptides involved in various physiological processes related to obesity. The aim of this study was to investigate the consequences of chronic orexin-A treatment in mouse models.
Methods
Female wild-type C57BL/6 mice that were obesity-prone or obesity-resistant and mice that were deficient for orexin receptors were fed with a high-fat diet. Glucose tolerance, indirect calorimetry, expression of brain neuropeptides and receptors, microglial activation, and microbiota were determined to evaluate the role of orexins on metabolic flexibility.
Results
Orexin-A reduces weight gain in obesity-prone mice. This reduction is associated with a decrease in body fat, food intake, steatosis, and insulin resistance, as well as alterations of intestinal microbiota composition. A decreased expression of orexin receptors and neuropeptides involved in food intake was also observed in the hypothalamus.
Conclusions
Our data support the notion that orexin receptor signaling is involved in different aspects of energy metabolism and can mitigate several dysfunctions associated with obesity, suggesting that orexin receptors can represent new targets for obesity treatment.
{"title":"Orexins mitigate obesity-associated dysfunctions in mice","authors":"Anne Blais, Isabelle Denis, Mireille Andriamihaja, Valérie Gratio, Gaelle Champeil-Potokar, Samira Laouirem, Anais Chassac, Anne Couvelard, Valérie Paradis, Thierry Voisin, Anne-Marie Davila, Alain Couvineau","doi":"10.1002/oby.24120","DOIUrl":"10.1002/oby.24120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Obesity is a chronic disease that affects more than 400 million adults with severe comorbidities. The search for new treatments to reduce its negative consequences is necessary. Orexins are hypothalamic neuropeptides involved in various physiological processes related to obesity. The aim of this study was to investigate the consequences of chronic orexin-A treatment in mouse models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Female wild-type C57BL/6 mice that were obesity-prone or obesity-resistant and mice that were deficient for orexin receptors were fed with a high-fat diet. Glucose tolerance, indirect calorimetry, expression of brain neuropeptides and receptors, microglial activation, and microbiota were determined to evaluate the role of orexins on metabolic flexibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Orexin-A reduces weight gain in obesity-prone mice. This reduction is associated with a decrease in body fat, food intake, steatosis, and insulin resistance, as well as alterations of intestinal microbiota composition. A decreased expression of orexin receptors and neuropeptides involved in food intake was also observed in the hypothalamus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data support the notion that orexin receptor signaling is involved in different aspects of energy metabolism and can mitigate several dysfunctions associated with obesity, suggesting that orexin receptors can represent new targets for obesity treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1897-1909"},"PeriodicalIF":4.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309512","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}
Brandon M. Roberts, Adam W. Potter, Geoffrey C. Chin, Karl E. Friedl
{"title":"Antiobesity medications in active-duty military personnel","authors":"Brandon M. Roberts, Adam W. Potter, Geoffrey C. Chin, Karl E. Friedl","doi":"10.1002/oby.24136","DOIUrl":"10.1002/oby.24136","url":null,"abstract":"","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1797-1798"},"PeriodicalIF":4.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265669","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}
Nicola L. Hawley, Kima Faasalele-Savusa, Mata'uitafa Faiai, Lynette Suiaunoa-Scanlan, Miracle Loia, Jeannette R. Ickovics, Erica Kocher, Christopher Piel, Madison Mahoney, Rachel Suss, Marcela Trocha, Rochelle K. Rosen, Bethel T. Muasau-Howard
Objective
The objective of this study was to determine the preliminary effectiveness of an intervention to mitigate adverse pregnancy outcomes associated with pre-pregnancy obesity in American Samoa.
Methods
We enrolled n = 80 low-risk pregnant women at <14 weeks' gestation. A complete case analysis was conducted with randomized group assignment (group prenatal care-delivered intervention vs. one-on-one usual care) as the independent variable. Primary outcomes were gestational weight gain and postpartum weight change. Secondary outcomes included gestational diabetes screening and exclusive breastfeeding at 6 weeks post partum. Other outcomes reported include gestational diabetes incidence, preterm birth, mode of birth, infant birth weight, and macrosomia.
Results
Gestational weight gain was lower among group versus usual care participants (mean [SD], 9.46 [7.24] kg vs. 14.40 [8.23] kg; p = 0.10); postpartum weight change did not differ between groups. Although the proportion of women who received adequate gestational diabetes screening (78.4% group; 65.6% usual care) was similar, there were clinically important between-group differences in exclusive breastfeeding (44.4% group; 25% usual care), incidence of gestational diabetes (27.3% group; 40.0% usual care), and macrosomia (8.3% group; 29.0% usual care).
Conclusions
It may be possible to address multiple risk factors related to intergenerational transmission of obesity in this high-risk setting using a group care-delivered intervention.
{"title":"A group prenatal care intervention reduces gestational weight gain and gestational diabetes in American Samoan women","authors":"Nicola L. Hawley, Kima Faasalele-Savusa, Mata'uitafa Faiai, Lynette Suiaunoa-Scanlan, Miracle Loia, Jeannette R. Ickovics, Erica Kocher, Christopher Piel, Madison Mahoney, Rachel Suss, Marcela Trocha, Rochelle K. Rosen, Bethel T. Muasau-Howard","doi":"10.1002/oby.24102","DOIUrl":"10.1002/oby.24102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to determine the preliminary effectiveness of an intervention to mitigate adverse pregnancy outcomes associated with pre-pregnancy obesity in American Samoa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We enrolled <i>n</i> = 80 low-risk pregnant women at <14 weeks' gestation. A complete case analysis was conducted with randomized group assignment (group prenatal care-delivered intervention vs. one-on-one usual care) as the independent variable. Primary outcomes were gestational weight gain and postpartum weight change. Secondary outcomes included gestational diabetes screening and exclusive breastfeeding at 6 weeks post partum. Other outcomes reported include gestational diabetes incidence, preterm birth, mode of birth, infant birth weight, and macrosomia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gestational weight gain was lower among group versus usual care participants (mean [SD], 9.46 [7.24] kg vs. 14.40 [8.23] kg; <i>p</i> = 0.10); postpartum weight change did not differ between groups. Although the proportion of women who received adequate gestational diabetes screening (78.4% group; 65.6% usual care) was similar, there were clinically important between-group differences in exclusive breastfeeding (44.4% group; 25% usual care), incidence of gestational diabetes (27.3% group; 40.0% usual care), and macrosomia (8.3% group; 29.0% usual care).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>It may be possible to address multiple risk factors related to intergenerational transmission of obesity in this high-risk setting using a group care-delivered intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1833-1843"},"PeriodicalIF":4.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224412","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}
Philippa Garbutt, Malgorzata Cyranka, Johanna Michl, Yuko Maejima, Natascia Vedovato, Kenju Shimomura, Pawel Swietach, Heidi de Wet
Objective
The intestinal luminal pH profile varies from stomach to rectum and becomes disrupted in diseases. However, little is known about the pH dependence of incretin hormone secretion, with most in vitro studies having failed to consider this modulatory factor or having used nonphysiological buffer systems. Here, we report the extracellular pH (pHe) dependence of glucagon-like peptide-1 (GLP-1) exocytosis from L cells.
Methods
The pHe dependence of GLP-1 release from GLUTag cells and murine ex vivo primary gut cultures was detected by ELISA. GLP-1 release was measured over a range of pHe under a physiological (CO2/HCO3−) buffering regime and in its absence (HEPES buffer). The relationship between intracellular pH (pHi) and pHe was mapped given that at least some component of pH sensitivity is likely to be intracellular.
Results
GLP-1 secretion from L cells was pHe-dependent and stimulated under alkaline conditions. In the absence of glucose or extracellular calcium, secretion remained at a pHe-insensitive baseline. pHi followed changes in pHe, but the relationship was offset to more alkaline levels in the absence of CO2/HCO3− buffer and became shallower if [Cl−] changes that normally accompany [HCO3−] changes were compensated iso-osmotically with gluconate.
Conclusions
GLP-1 secretion is sensitive to pHe and the buffer present. Exploiting this mechanism therapeutically may benefit patients with obesity.
{"title":"The release of GLP-1 from gut L cells is inhibited by low extracellular pH","authors":"Philippa Garbutt, Malgorzata Cyranka, Johanna Michl, Yuko Maejima, Natascia Vedovato, Kenju Shimomura, Pawel Swietach, Heidi de Wet","doi":"10.1002/oby.24125","DOIUrl":"10.1002/oby.24125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The intestinal luminal pH profile varies from stomach to rectum and becomes disrupted in diseases. However, little is known about the pH dependence of incretin hormone secretion, with most in vitro studies having failed to consider this modulatory factor or having used nonphysiological buffer systems. Here, we report the extracellular pH (pHe) dependence of glucagon-like peptide-1 (GLP-1) exocytosis from L cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The pHe dependence of GLP-1 release from GLUTag cells and murine ex vivo primary gut cultures was detected by ELISA. GLP-1 release was measured over a range of pHe under a physiological (CO<sub>2</sub>/HCO<sub>3</sub><sup>−</sup>) buffering regime and in its absence (HEPES buffer). The relationship between intracellular pH (pHi) and pHe was mapped given that at least some component of pH sensitivity is likely to be intracellular.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GLP-1 secretion from L cells was pHe-dependent and stimulated under alkaline conditions. In the absence of glucose or extracellular calcium, secretion remained at a pHe-insensitive baseline. pHi followed changes in pHe, but the relationship was offset to more alkaline levels in the absence of CO<sub>2</sub>/HCO<sub>3</sub><sup>−</sup> buffer and became shallower if [Cl<sup>−</sup>] changes that normally accompany [HCO<sub>3</sub><sup>−</sup>] changes were compensated iso-osmotically with gluconate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GLP-1 secretion is sensitive to pHe and the buffer present. Exploiting this mechanism therapeutically may benefit patients with obesity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1819-1824"},"PeriodicalIF":4.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142250","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}
Sujing Wang, Jie Shen, Woon-Puay Koh, Jian-Min Yuan, Xiang Gao, Yinshun Peng, Yaqing Xu, Shuxiao Shi, Yue Huang, Ying Dong, Victor W. Zhong
Objective
The objective of this study was to compare race- and ethnicity-specific BMI cutoffs for the three classes of obesity based on equivalent risk of type 2 diabetes (T2D).
Methods
Participants without T2D were included from the UK Biobank, the China Health and Nutrition Survey, and the Singapore Chinese Health Study. Poisson regressions with restricted cubic splines were applied to determine BMI cutoffs for each non-White race and ethnicity for equivalent incidence rates of T2D at BMI values of 30.0, 35.0, and 40.0 kg/m2 in White adults.
Results
During a median follow-up of 13.8 years among 507,763 individuals, 5.2% developed T2D. In women, BMI cutoffs for an equivalent incidence rate of T2D as observed at 40.0 kg/m2 in White adults were 31.6 kg/m2 in Black, 29.2 kg/m2 in British Chinese, 27.3 kg/m2 in South Asian, 26.9 kg/m2 in Native Chinese, and 25.1 kg/m2 in Singapore Chinese adults. In men, the corresponding BMI cutoffs were 31.9 kg/m2 in Black, 30.6 kg/m2 in British Chinese, 29.0 kg/m2 in South Asian, 29.6 kg/m2 in Native Chinese, and 27.6 kg/m2 in Singapore Chinese adults. The race and ethnicity order was consistent when equivalent BMI cutoffs were estimated for class I and II obesity.
Conclusions
Establishing a race- and ethnicity-tailored classification of the three classes of obesity is urgently needed.
{"title":"Comparison of race- and ethnicity-specific BMI cutoffs for categorizing obesity severity: a multicountry prospective cohort study","authors":"Sujing Wang, Jie Shen, Woon-Puay Koh, Jian-Min Yuan, Xiang Gao, Yinshun Peng, Yaqing Xu, Shuxiao Shi, Yue Huang, Ying Dong, Victor W. Zhong","doi":"10.1002/oby.24129","DOIUrl":"10.1002/oby.24129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to compare race- and ethnicity-specific BMI cutoffs for the three classes of obesity based on equivalent risk of type 2 diabetes (T2D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants without T2D were included from the UK Biobank, the China Health and Nutrition Survey, and the Singapore Chinese Health Study. Poisson regressions with restricted cubic splines were applied to determine BMI cutoffs for each non-White race and ethnicity for equivalent incidence rates of T2D at BMI values of 30.0, 35.0, and 40.0 kg/m<sup>2</sup> in White adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During a median follow-up of 13.8 years among 507,763 individuals, 5.2% developed T2D. In women, BMI cutoffs for an equivalent incidence rate of T2D as observed at 40.0 kg/m<sup>2</sup> in White adults were 31.6 kg/m<sup>2</sup> in Black, 29.2 kg/m<sup>2</sup> in British Chinese, 27.3 kg/m<sup>2</sup> in South Asian, 26.9 kg/m<sup>2</sup> in Native Chinese, and 25.1 kg/m<sup>2</sup> in Singapore Chinese adults. In men, the corresponding BMI cutoffs were 31.9 kg/m<sup>2</sup> in Black, 30.6 kg/m<sup>2</sup> in British Chinese, 29.0 kg/m<sup>2</sup> in South Asian, 29.6 kg/m<sup>2</sup> in Native Chinese, and 27.6 kg/m<sup>2</sup> in Singapore Chinese adults. The race and ethnicity order was consistent when equivalent BMI cutoffs were estimated for class I and II obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Establishing a race- and ethnicity-tailored classification of the three classes of obesity is urgently needed.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1958-1966"},"PeriodicalIF":4.2,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121472","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}
Maria J. Pereira, Argyri Mathioudaki, Alicia G. Otero, Padma Priya Duvvuri, Milica Vranic, Amir Sedigh, Jan W. Eriksson, Maria K. Svensson
Objective
The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins.
Methods
Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed.
Results
RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT.
Conclusions
The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders.
{"title":"Renal sinus adipose tissue: exploratory study of metabolic features and transcriptome compared with omental and subcutaneous adipose tissue","authors":"Maria J. Pereira, Argyri Mathioudaki, Alicia G. Otero, Padma Priya Duvvuri, Milica Vranic, Amir Sedigh, Jan W. Eriksson, Maria K. Svensson","doi":"10.1002/oby.24114","DOIUrl":"10.1002/oby.24114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1870-1884"},"PeriodicalIF":4.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116633","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}
Ashley S. Meakin, Peter W. Nathanielsz, Cun Li, Hillary F. Huber, Vicki L. Clifton, Michael D. Wiese, Janna L. Morrison
Objective
Maternal obesity (MO) increases the risk of later-life liver disease in offspring, especially in males. This may be due to impaired cytochrome P450 (CYP) enzyme activity driven by an altered maternal-fetal hormonal milieu. MO increases fetal cortisol concentrations that may increase CYP activity; however, glucocorticoid receptor (GR)-mediated signaling can be modulated by alternative GR isoform expression. We hypothesized that MO induces sex-specific changes in GR isoform expression and localization that contribute to reduced hepatic CYP activity.
Methods
Nonpregnant, nulliparous female baboons were assigned to either an ad libitum control diet or a high-fat, high-energy diet (HF-HED) at 9 months pre pregnancy. At 165 days' gestation (term = 180 days), fetal liver samples were collected (n = 6/sex/group). CYP activity was quantified using functional assays, and GR was measured using quantitative RT-PCR and Western blot.
Results
CYP3A activity was reduced in the HF-HED group, whereas CYP2B6 activity was reduced in HF-HED males only. Total GR expression was increased in the HF-HED group. Relative nuclear expression of the antagonistic GR isoform GRβ was increased in HF-HED males only.
Conclusions
Reduced CYP activity in HF-HED males may be driven in part by dampened hepatic-specific glucocorticoid signaling via altered GR isoform expression. These findings highlight targetable mechanisms that may reduce later-life sex-specific disease risk.
目的：母体肥胖（MO）会增加后代患晚年肝病的风险，尤其是男性。这可能是由于母胎激素环境改变导致细胞色素 P450（CYP）酶活性受损。MO会增加胎儿皮质醇的浓度，从而可能增加CYP的活性；然而，糖皮质激素受体（GR）介导的信号传导可通过GR异构体的替代表达来调节。我们假设 MO 会诱导 GR 同工酶表达和定位的性别特异性变化，从而导致肝脏 CYP 活性降低：方法：在妊娠前 9 个月，将未怀孕的空腹雌性狒狒分配到自由控制饮食或高脂肪、高能量饮食（HF-HED）中。在妊娠 165 天（足月 = 180 天）时，收集胎儿肝脏样本（n = 6 个/性别/组）。采用功能测定法对 CYP 活性进行量化，并采用定量 RT-PCR 和 Western 印迹法测定 GR：结果：HF-HED 组的 CYP3A 活性降低，而仅 HF-HED 男性的 CYP2B6 活性降低。HF-HED 组的 GR 总表达量增加。仅在 HF-HED 组男性中，拮抗 GR 同工酶 GRβ 的相对核表达增加：结论：HF-HED 男性体内 CYP 活性降低的部分原因可能是肝脏特异性糖皮质激素信号通过 GR 同工酶表达的改变而受到抑制。这些发现突显了可降低晚年性别特异性疾病风险的靶向机制。
{"title":"Maternal obesogenic diet during pregnancy and its impact on fetal hepatic function in baboons","authors":"Ashley S. Meakin, Peter W. Nathanielsz, Cun Li, Hillary F. Huber, Vicki L. Clifton, Michael D. Wiese, Janna L. Morrison","doi":"10.1002/oby.24124","DOIUrl":"10.1002/oby.24124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Maternal obesity (MO) increases the risk of later-life liver disease in offspring, especially in males. This may be due to impaired cytochrome P450 (CYP) enzyme activity driven by an altered maternal-fetal hormonal milieu. MO increases fetal cortisol concentrations that may increase CYP activity; however, glucocorticoid receptor (GR)-mediated signaling can be modulated by alternative GR isoform expression. We hypothesized that MO induces sex-specific changes in GR isoform expression and localization that contribute to reduced hepatic CYP activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nonpregnant, nulliparous female baboons were assigned to either an ad libitum control diet or a high-fat, high-energy diet (HF-HED) at 9 months pre pregnancy. At 165 days' gestation (term = 180 days), fetal liver samples were collected (<i>n</i> = 6/sex/group). CYP activity was quantified using functional assays, and GR was measured using quantitative RT-PCR and Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CYP3A activity was reduced in the HF-HED group, whereas CYP2B6 activity was reduced in HF-HED males only. Total <i>GR</i> expression was increased in the HF-HED group. Relative nuclear expression of the antagonistic GR isoform GRβ was increased in HF-HED males only.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Reduced CYP activity in HF-HED males may be driven in part by dampened hepatic-specific glucocorticoid signaling via altered GR isoform expression. These findings highlight targetable mechanisms that may reduce later-life sex-specific disease risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1910-1922"},"PeriodicalIF":4.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116632","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}
L. Stefan Lohmander, Markku Peltonen, Johanna C. Andersson-Assarsson, Kajsa Sjöholm, Magdalena Taube, Peter Jacobson, Per-Arne Svensson, Lena M. S. Carlsson, Sofie Ahlin
Objective
The objective of this study was to study the recovery from, and incidence of, work-restricting musculoskeletal pain after bariatric surgery compared with usual obesity care.
Methods
Pain in different body regions was monitored using questionnaires in the nonrandomized, prospective, controlled Swedish Obese Subjects (SOS) study, which included 2007 participants treated with bariatric surgery and a matched control group of 2040 participants receiving usual obesity care at primary health care centers. Self-reported pain in the neck and shoulders, back, hips, knees, and ankles was captured from questionnaires administered at baseline and after 1, 2, 3, 4, 6, 8, 10, 15, and 20 years.
Results
Compared with matched controls, bariatric surgery was associated with better recovery from baseline work-restricting knee and ankle pain in both the short (1–4 years) and long term (up to 20 years), as well as from back and hip pain in the short term. In participants without pain at baseline, bariatric surgery was associated with a lower incidence of developing new pain in the knee and ankle in the short and long term.
Conclusions
Bariatric surgery was associated with better recovery from pain, primarily in weight-bearing joints, as well as with prevention of pain development in the knee and ankle compared with matched controls receiving usual obesity care.
{"title":"Work-restricting musculoskeletal pain after bariatric surgery or usual obesity care in the Swedish Obese Subjects study","authors":"L. Stefan Lohmander, Markku Peltonen, Johanna C. Andersson-Assarsson, Kajsa Sjöholm, Magdalena Taube, Peter Jacobson, Per-Arne Svensson, Lena M. S. Carlsson, Sofie Ahlin","doi":"10.1002/oby.24128","DOIUrl":"10.1002/oby.24128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to study the recovery from, and incidence of, work-restricting musculoskeletal pain after bariatric surgery compared with usual obesity care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Pain in different body regions was monitored using questionnaires in the nonrandomized, prospective, controlled Swedish Obese Subjects (SOS) study, which included 2007 participants treated with bariatric surgery and a matched control group of 2040 participants receiving usual obesity care at primary health care centers. Self-reported pain in the neck and shoulders, back, hips, knees, and ankles was captured from questionnaires administered at baseline and after 1, 2, 3, 4, 6, 8, 10, 15, and 20 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with matched controls, bariatric surgery was associated with better recovery from baseline work-restricting knee and ankle pain in both the short (1–4 years) and long term (up to 20 years), as well as from back and hip pain in the short term. In participants without pain at baseline, bariatric surgery was associated with a lower incidence of developing new pain in the knee and ankle in the short and long term.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Bariatric surgery was associated with better recovery from pain, primarily in weight-bearing joints, as well as with prevention of pain development in the knee and ankle compared with matched controls receiving usual obesity care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 10","pages":"1844-1856"},"PeriodicalIF":4.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116634","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}
Çiğdem Köroğlu, Michael Traurig, Yunhua L. Muller, Samantha E. Day, Paolo Piaggi, Kim Wiedrich, Laura Vazquez, Robert L. Hanson, Cristopher V. Van Hout, Anna Alkelai, Alan R. Shuldiner, Clifton Bogardus, Leslie J. Baier
Objective
Rare cases of monogenic obesity, which may respond to specific therapeutics, can remain undetected in populations in which polygenic obesity is prevalent. This study examined rare DNA variation in established monogenic obesity genes within a community using whole-exome sequence data from 6803 longitudinally studied individuals.
Methods
Exome data across 15 monogenic obesity genes were analyzed for nonsynonymous variants observed in any child with a maximum BMI z score > 2 (N = 279) but not observed in a child with a maximum BMI z score ≤ 0 (n = 1542) or that occurred in adults in the top 5th percentile of BMI (n = 263) but not in adults below the median BMI (n = 2629). Variants were then functionally analyzed using luciferase assays.
Results
The comparisons between cases of obesity and controls identified eight missense variants in six genes: DYRK1B, KSR2, MC4R, NTRK2, PCSK1, and SIM1. Among these, MC4R p.A303P and p.R165G were previously shown to impair MC4R function. Functional analyses of the remaining six variants suggest that KSR2 p.I402F and p.T193I and NTRK2 p.S249Y alter protein function.
Conclusions
In addition to MC4R, rare missense variants in KSR2 and NTRK2 may potentially explain the severe obesity observed for the carriers.
{"title":"Identification and functional validation of rare coding variants in genes linked to monogenic obesity","authors":"Çiğdem Köroğlu, Michael Traurig, Yunhua L. Muller, Samantha E. Day, Paolo Piaggi, Kim Wiedrich, Laura Vazquez, Robert L. Hanson, Cristopher V. Van Hout, Anna Alkelai, Alan R. Shuldiner, Clifton Bogardus, Leslie J. Baier","doi":"10.1002/oby.24101","DOIUrl":"10.1002/oby.24101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Rare cases of monogenic obesity, which may respond to specific therapeutics, can remain undetected in populations in which polygenic obesity is prevalent. This study examined rare DNA variation in established monogenic obesity genes within a community using whole-exome sequence data from 6803 longitudinally studied individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Exome data across 15 monogenic obesity genes were analyzed for nonsynonymous variants observed in any child with a maximum BMI <i>z</i> score > 2 (<i>N</i> = 279) but not observed in a child with a maximum BMI <i>z</i> score ≤ 0 (<i>n</i> = 1542) or that occurred in adults in the top 5th percentile of BMI (<i>n</i> = 263) but not in adults below the median BMI (<i>n</i> = 2629). Variants were then functionally analyzed using luciferase assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The comparisons between cases of obesity and controls identified eight missense variants in six genes: <i>DYRK1B</i>, <i>KSR2</i>, <i>MC4R</i>, <i>NTRK2</i>, <i>PCSK1</i>, and <i>SIM1</i>. Among these, <i>MC4R</i> p.A303P and p.R165G were previously shown to impair MC4R function. Functional analyses of the remaining six variants suggest that <i>KSR2</i> p.I402F and p.T193I and <i>NTRK2</i> p.S249Y alter protein function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In addition to <i>MC4R</i>, rare missense variants in <i>KSR2</i> and <i>NTRK2</i> may potentially explain the severe obesity observed for the carriers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"32 9","pages":"1769-1777"},"PeriodicalIF":4.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082986","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}
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