Joshua Peterson, Jayashree Jena, Ayushi Sood, Shelly Roitershtein, David Smith, Renata O. Pereira
Objective
Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet-induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.
Methods
We generated mice simultaneously lacking the Opa1, Fgf21, and Gdf15 genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high-fat diet feeding.
Results
Young TKO mice fed regular chow had impaired glucose tolerance, while insulin sensitivity was unchanged. Notably, combined Fgf21 and Gdf15 deletion in OPA1 BKO significantly blunted the resistance to DIO and insulin resistance observed in OPA1 BKO mice.
Conclusions
FGF21 and GDF15 act synergistically to maintain glucose homeostasis and promote resistance to DIO in mice lacking OPA1 in BAT, highlighting the potential of combined therapies using FGF21 and GDF15 for the treatment of metabolic disorders.
{"title":"FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes","authors":"Joshua Peterson, Jayashree Jena, Ayushi Sood, Shelly Roitershtein, David Smith, Renata O. Pereira","doi":"10.1002/oby.70004","DOIUrl":"10.1002/oby.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet-induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We generated mice simultaneously lacking the <i>Opa1</i>, <i>Fgf21</i>, and <i>Gdf15</i> genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high-fat diet feeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Young TKO mice fed regular chow had impaired glucose tolerance, while insulin sensitivity was unchanged. Notably, combined <i>Fgf21</i> and <i>Gdf15</i> deletion in OPA1 BKO significantly blunted the resistance to DIO and insulin resistance observed in OPA1 BKO mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>FGF21 and GDF15 act synergistically to maintain glucose homeostasis and promote resistance to DIO in mice lacking OPA1 in BAT, highlighting the potential of combined therapies using FGF21 and GDF15 for the treatment of metabolic disorders.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1909-1920"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984430","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}
Brianna Johnson-Rabbett, Tirissa J. Reid, Edmond P. Wickham III, Judith Korner, Dana R. Brittan, Kimberly A. Gudzune
Objective
This study aimed to describe the characteristics of American Board of Obesity Medicine (ABOM) physician diplomates over the last 8 years (2017–2024).
Methods
Using the ABOM database, we conducted a cross-sectional study of physicians who achieved initial ABOM certification between 2017 and 2024. Characteristics included demographics, primary medical specialty, years of obesity medicine experience, patient population, and practice setting. We conducted descriptive analyses and compared current characteristics with estimates extracted from the published ABOM 5-year report (2012–2016).
Results
Overall, 8640 physicians achieved initial ABOM certification between 2017 and 2024; 2068 achieved certification between 2012 and 2016. Between the 2012–2016 and 2017–2024 groups, notable differences were increases in physicians under age 40 years (22.7% vs. 47.6%, respectively), women (52.8% vs. 64.0%, respectively), and practicing obesity medicine for less than 2 years at initial certification (40.2% vs. 68.3%, respectively). The most common primary medical specialties were internal medicine (32.4%), family medicine (29.2%), and internal medicine subspecialties (14.2%).
Conclusions
We found that recent ABOM diplomates are likely entering the field earlier in their careers and with fewer years of obesity medicine experience than the initial group. Future investigation is needed to understand how ABOM and other obesity organizations can best support these physicians in their transition to obesity medicine clinical practice.
{"title":"An Update on the American Board of Obesity Medicine (ABOM): 2017–2024","authors":"Brianna Johnson-Rabbett, Tirissa J. Reid, Edmond P. Wickham III, Judith Korner, Dana R. Brittan, Kimberly A. Gudzune","doi":"10.1002/oby.70013","DOIUrl":"10.1002/oby.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to describe the characteristics of American Board of Obesity Medicine (ABOM) physician diplomates over the last 8 years (2017–2024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the ABOM database, we conducted a cross-sectional study of physicians who achieved initial ABOM certification between 2017 and 2024. Characteristics included demographics, primary medical specialty, years of obesity medicine experience, patient population, and practice setting. We conducted descriptive analyses and compared current characteristics with estimates extracted from the published ABOM 5-year report (2012–2016).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 8640 physicians achieved initial ABOM certification between 2017 and 2024; 2068 achieved certification between 2012 and 2016. Between the 2012–2016 and 2017–2024 groups, notable differences were increases in physicians under age 40 years (22.7% vs. 47.6%, respectively), women (52.8% vs. 64.0%, respectively), and practicing obesity medicine for less than 2 years at initial certification (40.2% vs. 68.3%, respectively). The most common primary medical specialties were internal medicine (32.4%), family medicine (29.2%), and internal medicine subspecialties (14.2%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We found that recent ABOM diplomates are likely entering the field earlier in their careers and with fewer years of obesity medicine experience than the initial group. Future investigation is needed to understand how ABOM and other obesity organizations can best support these physicians in their transition to obesity medicine clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 11","pages":"2055-2060"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984492","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}
Francois Mifsud, Sarah Chalopin, Emilie Guillon, Pauline Faucher, Jean Muller, Johanne Le Bihan, Karine Clément, Christine Poitou
Objective
The melanocortin-4 receptor agonist setmelanotide has demonstrated effectiveness in phase 3 clinical trials for patients with monogenic obesity caused by biallelic variants in the leptin receptor (LEPR) and pro-opiomelanocortin (POMC), as well as for individuals with Bardet–Biedl syndrome (BBS). However, real-world evidence remains limited. This study evaluates the long-term effectiveness and safety of setmelanotide in patients who received treatment under a pre-marketing early-access authorization.
Methods
This ongoing prospective monocentric cohort includes 17 patients with obesity due to BBS (n = 11) or biallelic variants in LEPR (n = 4) or POMC (n = 2) who either started setmelanotide in routine care between 2022 and 2024 or continued therapy after participating in the RM-493-022 clinical trial. The average follow-up time was 14.4 months.
Results
Patients experienced a clinically significant weight reduction of 20% from their highest pre-treatment weight within the first year. Those previously treated in a clinical trial maintained their weight loss over time. Additionally, eating behavior improved, with significant reductions in hunger (−62%), food craving (−41%), and external eating evaluated by DEBQ. The overall safety profile was consistent with phase 3 trials data, without any new safety signals.
Conclusions
These findings confirm the drug's long-term clinical benefit and safety profile in a routine-care setting.
{"title":"Real-World Efficacy and Safety of Setmelanotide in Adults With Monogenic or Syndromic Obesity: A Prospective Cohort Study","authors":"Francois Mifsud, Sarah Chalopin, Emilie Guillon, Pauline Faucher, Jean Muller, Johanne Le Bihan, Karine Clément, Christine Poitou","doi":"10.1002/oby.70002","DOIUrl":"10.1002/oby.70002","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The melanocortin-4 receptor agonist setmelanotide has demonstrated effectiveness in phase 3 clinical trials for patients with monogenic obesity caused by biallelic variants in the leptin receptor (LEPR) and pro-opiomelanocortin (POMC), as well as for individuals with Bardet–Biedl syndrome (BBS). However, real-world evidence remains limited. This study evaluates the long-term effectiveness and safety of setmelanotide in patients who received treatment under a pre-marketing early-access authorization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This ongoing prospective monocentric cohort includes 17 patients with obesity due to BBS (<i>n</i> = 11) or biallelic variants in <i>LEPR</i> (<i>n</i> = 4) or <i>POMC</i> (<i>n</i> = 2) who either started setmelanotide in routine care between 2022 and 2024 or continued therapy after participating in the RM-493-022 clinical trial. The average follow-up time was 14.4 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients experienced a clinically significant weight reduction of 20% from their highest pre-treatment weight within the first year. Those previously treated in a clinical trial maintained their weight loss over time. Additionally, eating behavior improved, with significant reductions in hunger (−62%), food craving (−41%), and external eating evaluated by DEBQ. The overall safety profile was consistent with phase 3 trials data, without any new safety signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings confirm the drug's long-term clinical benefit and safety profile in a routine-care setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1865-1872"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983688","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}
{"title":"CRISPLD2: A Weight Loss-Induced Adipokine With Antifibrotic Capabilities in Adipose Tissue","authors":"David Mendoza, Jacqueline M. Stephens","doi":"10.1002/oby.70034","DOIUrl":"10.1002/oby.70034","url":null,"abstract":"","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 11","pages":"2027-2028"},"PeriodicalIF":4.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984468","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}
Matthew J. Breit, Zhaoxing Pan, Danielle M. Ostendorf, Jared H. Dahle, Victoria A. Catenacci, Seth A. Creasy, Edward L. Melanson
Objective
The doubly labeled water (DLW) intake-balance method estimates energy intake (EI) during weight loss using the time-weighted average of total daily energy expenditure (TDEE) and changes in body energy stores. Because TDEE declines rapidly during the early phase of weight loss, an early additional measurement is recommended. This study aimed to develop regression models that estimate time-weighted TDEE using fewer interim measurements and determine if EI accuracy is maintained during a 12-month weight loss intervention.
Methods
Data from a behavioral weight loss intervention (Dietary Caloric Restriction versus intermittent Fasting Trial, “DRIFT”) were used. TDEE, body weight, and body composition were measured at months 0, 1, 6, and 12. Regression models using only two or three time points were used to estimate time-weighted TDEE at months 6 and 12, respectively. Models were validated using bootstrap sampling, and time-weighted TDEE and percent caloric restriction (% CR) were compared to a reference approach.
Results
Models demonstrated strong predictive performance (R2 = 0.911–0.982). Limits of agreement with the reference model were 121.1–274.5 kcal/day for TDEE and 4.5%–10.3% for % CR, without significant bias.
Conclusions
Using a regression modeling approach, we demonstrate the DLW intake-balance method maintains accuracy during weight loss without early-phase TDEE measurements.
{"title":"Using Time-Weighted Averages of Total Daily Energy Expenditure to Estimate Energy Intake During a Weight Loss Intervention","authors":"Matthew J. Breit, Zhaoxing Pan, Danielle M. Ostendorf, Jared H. Dahle, Victoria A. Catenacci, Seth A. Creasy, Edward L. Melanson","doi":"10.1002/oby.70008","DOIUrl":"10.1002/oby.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The doubly labeled water (DLW) intake-balance method estimates energy intake (EI) during weight loss using the time-weighted average of total daily energy expenditure (TDEE) and changes in body energy stores. Because TDEE declines rapidly during the early phase of weight loss, an early additional measurement is recommended. This study aimed to develop regression models that estimate time-weighted TDEE using fewer interim measurements and determine if EI accuracy is maintained during a 12-month weight loss intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from a behavioral weight loss intervention (<i>D</i>ietary Caloric <i>R</i>estriction versus intermittent <i>F</i>asting <i>T</i>rial, “DRIFT”) were used. TDEE, body weight, and body composition were measured at months 0, 1, 6, and 12. Regression models using only two or three time points were used to estimate time-weighted TDEE at months 6 and 12, respectively. Models were validated using bootstrap sampling, and time-weighted TDEE and percent caloric restriction (% CR) were compared to a reference approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Models demonstrated strong predictive performance (<i>R</i>\u0000 <sup>2</sup> = 0.911–0.982). Limits of agreement with the reference model were 121.1–274.5 kcal/day for TDEE and 4.5%–10.3% for % CR, without significant bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Using a regression modeling approach, we demonstrate the DLW intake-balance method maintains accuracy during weight loss without early-phase TDEE measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>\u0000 ClinicalTrials.gov identifier: NCT03411356</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 11","pages":"2093-2102"},"PeriodicalIF":4.7,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984100","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}
Mingyu Zhang, Izzuddin M. Aris, Andres Cardenas, Sheryl L. Rifas-Shiman, Pi-I Debby Lin, Long H. Ngo, Emily Oken, Stephen P. Juraschek, Marie-France Hivert
Objective
To examine the prospective associations of metal mixtures during pregnancy with midlife adiposity and explore metal-folate interactions.
Methods
In 500 participants from Project Viva, we measured six non-essential metals (arsenic, barium, cadmium, cesium, mercury, and lead) and five essential metals (copper, magnesium, manganese, selenium, and zinc) in red blood cells and folate in plasma collected during early pregnancy (mean gestational age: 10.0 weeks; mean age: 32.9 years). We assessed midlife (mean age: 51.2 years) adiposity using BMI and dual-energy X-ray absorptiometry (DXA) measures. We used multivariable-adjusted linear and multinomial logistic regression models to analyze individual exposures and Bayesian kernel machine regression to examine exposure mixtures.
Results
Higher arsenic, cesium, and mercury levels were associated with lower midlife DXA percentage fat, total fat mass index, and/or trunk fat mass index, even after adjustments for diet in pregnancy. We observed an antagonistic interaction between folate and arsenic: arsenic was associated with higher obesity risk at lower folate levels but lower obesity risk at higher folate levels. The essential metal mixture tended to be associated with lower midlife BMI and obesity risk.
Conclusions
Higher pregnancy levels of arsenic, cesium, mercury, and the mixture of essential metals were associated with lower midlife adiposity.
{"title":"Associations of Metal Mixtures During Early Pregnancy With Midlife Obesity and Body Composition: A Prospective Study","authors":"Mingyu Zhang, Izzuddin M. Aris, Andres Cardenas, Sheryl L. Rifas-Shiman, Pi-I Debby Lin, Long H. Ngo, Emily Oken, Stephen P. Juraschek, Marie-France Hivert","doi":"10.1002/oby.24368","DOIUrl":"10.1002/oby.24368","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To examine the prospective associations of metal mixtures during pregnancy with midlife adiposity and explore metal-folate interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In 500 participants from Project Viva, we measured six non-essential metals (arsenic, barium, cadmium, cesium, mercury, and lead) and five essential metals (copper, magnesium, manganese, selenium, and zinc) in red blood cells and folate in plasma collected during early pregnancy (mean gestational age: 10.0 weeks; mean age: 32.9 years). We assessed midlife (mean age: 51.2 years) adiposity using BMI and dual-energy X-ray absorptiometry (DXA) measures. We used multivariable-adjusted linear and multinomial logistic regression models to analyze individual exposures and Bayesian kernel machine regression to examine exposure mixtures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher arsenic, cesium, and mercury levels were associated with lower midlife DXA percentage fat, total fat mass index, and/or trunk fat mass index, even after adjustments for diet in pregnancy. We observed an antagonistic interaction between folate and arsenic: arsenic was associated with higher obesity risk at lower folate levels but lower obesity risk at higher folate levels. The essential metal mixture tended to be associated with lower midlife BMI and obesity risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher pregnancy levels of arsenic, cesium, mercury, and the mixture of essential metals were associated with lower midlife adiposity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1984-1994"},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984421","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}
Beth A. Griesel, Kylie Williams, Nagib Ahsan, Philipp E. Scherer, Ann Louise Olson, David P. Sparling
Objective
Both obesity and adipose tissue fibrosis are associated with insulin resistance, which can improve with weight loss. We previously found increased adipocyte-specific secretion of the novel adipokine CRISPLD2 during weight loss. In this study, we further explore the function of adipose CRISPLD2, which others suggest may regulate inflammation and fibrosis in a variety of tissues.
Methods
We designed mice with adipose-specific doxycycline-inducible overexpression of CRISPLD2 (CLD2AD) to assess adipose-specific effects on tissue structure and function on chow or high-fat diets. The effects of prolonged excess CRISPLD2 were determined after 7 months, including stromal vascular fraction analysis by single-cell RNA-seq. CRISPLD2 cell surface signaling was explored in 3T3-L1 adipocytes via transwell assays, and adipocyte binding partners were determined in unbiased binding screening by mass spectrometry.
Results
CLD2AD mice had decreased adipocyte size but unchanged fat mass. Long-term CRISPLD2 overexpression led to downregulation of collagen transcription and decreased fibrosis. CRISPLD2 induced Ifng transcription in adipocytes in vitro and bound multiple adipocyte cell surface proteins, including nucleolin. Finally, obese CLD2AD mice had decreased adipocyte size and improved glucose tolerance, with no change in fat mass.
Conclusions
These data suggest a model wherein CRISPLD2 can both regulate adipose tissue fibrosis and improve insulin sensitivity.
{"title":"CRISPLD2, a novel insulin-sensitizing adipokine that alters adipocyte size","authors":"Beth A. Griesel, Kylie Williams, Nagib Ahsan, Philipp E. Scherer, Ann Louise Olson, David P. Sparling","doi":"10.1002/oby.24342","DOIUrl":"10.1002/oby.24342","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Both obesity and adipose tissue fibrosis are associated with insulin resistance, which can improve with weight loss. We previously found increased adipocyte-specific secretion of the novel adipokine CRISPLD2 during weight loss. In this study, we further explore the function of adipose CRISPLD2, which others suggest may regulate inflammation and fibrosis in a variety of tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We designed mice with adipose-specific doxycycline-inducible overexpression of CRISPLD2 (CLD2<sup>AD</sup>) to assess adipose-specific effects on tissue structure and function on chow or high-fat diets. The effects of prolonged excess CRISPLD2 were determined after 7 months, including stromal vascular fraction analysis by single-cell RNA-seq. CRISPLD2 cell surface signaling was explored in 3T3-L1 adipocytes via transwell assays, and adipocyte binding partners were determined in unbiased binding screening by mass spectrometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CLD2<sup>AD</sup> mice had decreased adipocyte size but unchanged fat mass. Long-term CRISPLD2 overexpression led to downregulation of collagen transcription and decreased fibrosis. CRISPLD2 induced <i>Ifng</i> transcription in adipocytes in vitro and bound multiple adipocyte cell surface proteins, including nucleolin. Finally, obese CLD2<sup>AD</sup> mice had decreased adipocyte size and improved glucose tolerance, with no change in fat mass.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data suggest a model wherein CRISPLD2 can both regulate adipose tissue fibrosis and improve insulin sensitivity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 11","pages":"2139-2150"},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984440","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}
Olanrewaju Adeniran, Luis M. Nieto, Chima Amadi, Katherine Shepherd, Joshua Kirkpatrick, Kanith Farah, Farirai Marwizi, Budoor Alqinai, Sharon I. Narvaez, Samuel Mensah, Ayowumi Adekolu, Ethan M. Cohen, Raja S. Khan, Swapna Gayam, Lawrence E. Tabone, Laura Davisson
Objective
Roux-en-Y gastric bypass (RYGB) has been linked with increased alcohol-related outcomes, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with reduced risks. We performed the first multicenter retrospective cohort study to identify alcohol use outcomes of GLP-1 RAs post RYGB.
Methods
Using TriNetX, adults (≥ 18 years old) with obesity (BMI ≥ 30 kg/m2) who underwent RYGB between January 1, 2019, and May 31, 2023, were identified. Two cohorts were analyzed: patients initiated on GLP-1 RA versus non-GLP-1 RA users. Patients with other liver diseases and other bariatric surgeries were excluded. Covariates were balanced via propensity score matching (PSM). Participants were followed for at least 1 year post RYGB and GLP-1 RA initiation. Outcomes include the risk of alcohol use disorders (AUD), alcohol liver diseases (ALD), and all-cause mortality. Hazard ratio (HR) was calculated through Cox regression analysis.
Results
After PSM, 3438 were matched in each cohort. GLP-1 RA initiation was associated with a reduced incidence rate of AUD versus control (1.1% vs. 1.8%) (HR 0.77, [95% CI: 0.549–0.840, p = 0.041]) and all-cause mortality (1.2% versus 3.9%) (HR 0.497, [95% CI: 0.346–0.715, p = 0.039]).
Conclusions
Post RYGB, GLP-1 RAs provide the potential to reduce AUD and all-cause mortality.
{"title":"Alcoholic Use Disorder Outcomes After Roux-en-Y Gastric Bypass in Patients Taking GLP-1 RAs: A Multicenter Analysis","authors":"Olanrewaju Adeniran, Luis M. Nieto, Chima Amadi, Katherine Shepherd, Joshua Kirkpatrick, Kanith Farah, Farirai Marwizi, Budoor Alqinai, Sharon I. Narvaez, Samuel Mensah, Ayowumi Adekolu, Ethan M. Cohen, Raja S. Khan, Swapna Gayam, Lawrence E. Tabone, Laura Davisson","doi":"10.1002/oby.70001","DOIUrl":"10.1002/oby.70001","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Roux-en-Y gastric bypass (RYGB) has been linked with increased alcohol-related outcomes, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with reduced risks. We performed the first multicenter retrospective cohort study to identify alcohol use outcomes of GLP-1 RAs post RYGB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using TriNetX, adults (≥ 18 years old) with obesity (BMI ≥ 30 kg/m<sup>2</sup>) who underwent RYGB between January 1, 2019, and May 31, 2023, were identified. Two cohorts were analyzed: patients initiated on GLP-1 RA versus non-GLP-1 RA users. Patients with other liver diseases and other bariatric surgeries were excluded. Covariates were balanced via propensity score matching (PSM). Participants were followed for at least 1 year post RYGB and GLP-1 RA initiation. Outcomes include the risk of alcohol use disorders (AUD), alcohol liver diseases (ALD), and all-cause mortality. Hazard ratio (HR) was calculated through Cox regression analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After PSM, 3438 were matched in each cohort. GLP-1 RA initiation was associated with a reduced incidence rate of AUD versus control (1.1% vs. 1.8%) (HR 0.77, [95% CI: 0.549–0.840, <i>p</i> = 0.041]) and all-cause mortality (1.2% versus 3.9%) (HR 0.497, [95% CI: 0.346–0.715, <i>p</i> = 0.039]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Post RYGB, GLP-1 RAs provide the potential to reduce AUD and all-cause mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1886-1894"},"PeriodicalIF":4.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984427","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}
Tao Ju, Zhen Li, Xiaozu Zhang, Yang Liu, Xiaotian Gao, Haimo Zhang, Xizhen Wang, Xiaodong Sun, Xiaoli Wang
Obesity is a systemic disease that not only increases the incidence of diabetes and cardiovascular disease but also contributes to central nervous system disorders such as cognitive impairment, depression, and anxiety. Neuroimaging studies have confirmed that obesity leads to various forms of brain damage, as well as abnormalities in the function and metabolism of different brain regions. Multimodal neuroimaging, a collection of detection tools capable of visualizing neural diseases, has shown potential in diagnosing various brain disorders, and it provides insights from multiple perspectives to explore the pathological mechanisms of brain damage associated with obesity. Structural imaging techniques within multimodal imaging have identified changes in the volume and microstructure of the brain's gray and white matter. Functional imaging has detected abnormal activation and disrupted circuits in specific brain regions, while metabolic imaging has revealed neurochemical changes in the brain. In this review, we provide an overview of multimodal neuroimaging in obesity-related brain diseases, systematically analyzing these diseases from three aspects: structure, metabolism, and function. Additionally, we introduce novel multimodal imaging techniques that hold potential but have not yet been applied to obesity-related studies, aiming to provide a theoretical foundation for future clinical diagnosis and treatment.
{"title":"Multimodal Neuroimaging of Brain Structure, Metabolism, and Function in Obesity: Current Landscape and Future Perspectives","authors":"Tao Ju, Zhen Li, Xiaozu Zhang, Yang Liu, Xiaotian Gao, Haimo Zhang, Xizhen Wang, Xiaodong Sun, Xiaoli Wang","doi":"10.1002/oby.24353","DOIUrl":"10.1002/oby.24353","url":null,"abstract":"<div>\u0000 \u0000 <p>Obesity is a systemic disease that not only increases the incidence of diabetes and cardiovascular disease but also contributes to central nervous system disorders such as cognitive impairment, depression, and anxiety. Neuroimaging studies have confirmed that obesity leads to various forms of brain damage, as well as abnormalities in the function and metabolism of different brain regions. Multimodal neuroimaging, a collection of detection tools capable of visualizing neural diseases, has shown potential in diagnosing various brain disorders, and it provides insights from multiple perspectives to explore the pathological mechanisms of brain damage associated with obesity. Structural imaging techniques within multimodal imaging have identified changes in the volume and microstructure of the brain's gray and white matter. Functional imaging has detected abnormal activation and disrupted circuits in specific brain regions, while metabolic imaging has revealed neurochemical changes in the brain. In this review, we provide an overview of multimodal neuroimaging in obesity-related brain diseases, systematically analyzing these diseases from three aspects: structure, metabolism, and function. Additionally, we introduce novel multimodal imaging techniques that hold potential but have not yet been applied to obesity-related studies, aiming to provide a theoretical foundation for future clinical diagnosis and treatment.</p>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1833-1844"},"PeriodicalIF":4.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984456","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}
Steven B. Heymsfield, Philip J. Atherton, Sandra Christensen, Colleen Tewksbury, Amanda Velazquez, Jens Walter, Ellen E. Blaak
Obesity is a complex chronic disease requiring lifelong comprehensive treatment. In addition to lifestyle counseling that improves nutrition and physical activity, a promising new generation of obesity medications has been added to bariatric procedures as therapeutic options to achieve weight reduction and improve health outcomes. With the promise of effective and safe treatments comes the need to emphasize maximal reduction of body fat and minimal loss of vital body components, including skeletal muscle and bone. Nutrition is a critical aspect of obesity care and is leveraged to support preservation of lean tissues, such as skeletal muscle, through adequate, daily, high-quality protein intake and intake of key micronutrients. More targeted nutrition approaches that promote muscle protein synthesis include amino acid supplementation with leucine and its metabolite β-hydroxy β-methylbutyrate. Another potential target for support is the gut microbiome, as its adequate function is increasingly seen as playing a role in human health and metabolism. Obesity is a heterogenous disease, and there is considerable interest in specific metabolic phenotypes that might be used to tailor nutrition strategies. As research advances on these and other fronts, there is the potential to identify precision nutrition strategies for individualized, more effective approaches to lifelong obesity management.
{"title":"Evolution of multidisciplinary obesity treatments: past, present, and future role of nutrition","authors":"Steven B. Heymsfield, Philip J. Atherton, Sandra Christensen, Colleen Tewksbury, Amanda Velazquez, Jens Walter, Ellen E. Blaak","doi":"10.1002/oby.24340","DOIUrl":"10.1002/oby.24340","url":null,"abstract":"<p>Obesity is a complex chronic disease requiring lifelong comprehensive treatment. In addition to lifestyle counseling that improves nutrition and physical activity, a promising new generation of obesity medications has been added to bariatric procedures as therapeutic options to achieve weight reduction and improve health outcomes. With the promise of effective and safe treatments comes the need to emphasize maximal reduction of body fat and minimal loss of vital body components, including skeletal muscle and bone. Nutrition is a critical aspect of obesity care and is leveraged to support preservation of lean tissues, such as skeletal muscle, through adequate, daily, high-quality protein intake and intake of key micronutrients. More targeted nutrition approaches that promote muscle protein synthesis include amino acid supplementation with leucine and its metabolite β-hydroxy β-methylbutyrate. Another potential target for support is the gut microbiome, as its adequate function is increasingly seen as playing a role in human health and metabolism. Obesity is a heterogenous disease, and there is considerable interest in specific metabolic phenotypes that might be used to tailor nutrition strategies. As research advances on these and other fronts, there is the potential to identify precision nutrition strategies for individualized, more effective approaches to lifelong obesity management.</p>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 10","pages":"1819-1832"},"PeriodicalIF":4.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884705","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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