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":null,"pages":null},"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}
Jonathan Alessi, Mario Dzemidzic, Jaroslaw Harezlak, David A. Kareken, Robert V. Considine
Objective
Bariatric surgery reduces sweet-liking, but mechanisms remain unclear. We examined related brain responses.
Methods
A total of 24 nondiabetic bariatric surgery and 21 control participants with normal weight to overweight were recruited for an observational controlled cohort study. They underwent sucrose taste testing outside the scanner followed by stimulation with 0.40M and 0.10M sucrose compared with water during functional magnetic resonance imaging. A total of 21 bariatric participants repeated these procedures after surgery.
Results
Perceived sweet intensity was not different among the control, presurgery, or postsurgery groups. Bariatric participants' preferred sweet concentration decreased after surgery (0.52M to 0.29M; p = 0.008). Brain reward system (ventral tegmental area, ventral striatum, and orbitofrontal cortex) region of interest analysis showed that 0.40M sucrose activation (but not 0.10M) decreased after surgery. Sensory region (primary somatosensory and primary taste cortex) 0.40M sucrose activation was unchanged by surgery and did not differ between control and bariatric participants. Primary taste cortex activation to 0.10M sucrose solution was greater in postsurgical bariatric participants compared with control participants.
Conclusions
Bariatric surgery reduces the reward system response to sweet taste in women with obesity without affecting activity in sensory regions, which is consistent with reduced drive to consume sweet foods.
{"title":"Neural processing of sweet taste in reward regions is reduced following bariatric surgery","authors":"Jonathan Alessi, Mario Dzemidzic, Jaroslaw Harezlak, David A. Kareken, Robert V. Considine","doi":"10.1002/oby.24103","DOIUrl":"10.1002/oby.24103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Bariatric surgery reduces sweet-liking, but mechanisms remain unclear. We examined related brain responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 24 nondiabetic bariatric surgery and 21 control participants with normal weight to overweight were recruited for an observational controlled cohort study. They underwent sucrose taste testing outside the scanner followed by stimulation with 0.40M and 0.10M sucrose compared with water during functional magnetic resonance imaging. A total of 21 bariatric participants repeated these procedures after surgery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Perceived sweet intensity was not different among the control, presurgery, or postsurgery groups. Bariatric participants' preferred sweet concentration decreased after surgery (0.52M to 0.29M; <i>p</i> = 0.008). Brain reward system (ventral tegmental area, ventral striatum, and orbitofrontal cortex) region of interest analysis showed that 0.40M sucrose activation (but not 0.10M) decreased after surgery. Sensory region (primary somatosensory and primary taste cortex) 0.40M sucrose activation was unchanged by surgery and did not differ between control and bariatric participants. Primary taste cortex activation to 0.10M sucrose solution was greater in postsurgical bariatric participants compared with control participants.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Bariatric surgery reduces the reward system response to sweet taste in women with obesity without affecting activity in sensory regions, which is consistent with reduced drive to consume sweet foods.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082988","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}
Franz Duca, Katharina Mascherbauer, Carolina Donà, Matthias Koschutnik, Christina Binder, Christian Nitsche, Kseniya Halavina, Dietrich Beitzke, Christian Loewe, Philipp Bartko, Elisabeth Waldmann, Julia Mascherbauer, Christian Hengstenberg, Andreas Kammerlander
Objective
Epicardial adipose tissue (EAT) quantity is associated with poor cardiovascular outcomes. However, the quality of EAT may be of incremental prognostic value. Cardiac magnetic resonance (CMR) is the gold standard for tissue characterization but has never been applied for EAT quality assessment. We aimed to investigate EAT quality measured on CMR T1 mapping as a predictor of poor outcomes in an all-comer cohort.
Methods
We investigated the association of EAT area and EAT T1 times (EAT-T1) with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all-cause death.
Results
A total of 966 participants were included (47.2% female; mean age: 58.4 years) in this prospective observational CMR registry. Mean EAT area and EAT-T1 were 7.3 cm2 and 268 ms, respectively. On linear regression, EAT-T1 was not associated with markers of obesity, dyslipidemia, or comorbidities such as diabetes (p > 0.05 for all). During a follow-up of 57.7 months, a total of 280 (29.0%) events occurred. EAT-T1 was independently associated (adjusted hazard ratio per SD: 1.202; 95% CI: 1.022–1.413; p = 0.026) with the composite endpoint when adjusted for established clinical risk.
Conclusions
EAT quality (as assessed via CMR T1 times), but not EAT quantity, is independently associated with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all-cause death.
{"title":"Association of epicardial adipose tissue on magnetic resonance imaging with cardiovascular outcomes: Quality over quantity?","authors":"Franz Duca, Katharina Mascherbauer, Carolina Donà, Matthias Koschutnik, Christina Binder, Christian Nitsche, Kseniya Halavina, Dietrich Beitzke, Christian Loewe, Philipp Bartko, Elisabeth Waldmann, Julia Mascherbauer, Christian Hengstenberg, Andreas Kammerlander","doi":"10.1002/oby.24105","DOIUrl":"10.1002/oby.24105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Epicardial adipose tissue (EAT) quantity is associated with poor cardiovascular outcomes. However, the quality of EAT may be of incremental prognostic value. Cardiac magnetic resonance (CMR) is the gold standard for tissue characterization but has never been applied for EAT quality assessment. We aimed to investigate EAT quality measured on CMR T1 mapping as a predictor of poor outcomes in an all-comer cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the association of EAT area and EAT T1 times (EAT-T1) with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all-cause death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 966 participants were included (47.2% female; mean age: 58.4 years) in this prospective observational CMR registry. Mean EAT area and EAT-T1 were 7.3 cm<sup>2</sup> and 268 ms, respectively. On linear regression, EAT-T1 was not associated with markers of obesity, dyslipidemia, or comorbidities such as diabetes (<i>p</i> > 0.05 for all). During a follow-up of 57.7 months, a total of 280 (29.0%) events occurred. EAT-T1 was independently associated (adjusted hazard ratio per SD: 1.202; 95% CI: 1.022–1.413; <i>p</i> = 0.026) with the composite endpoint when adjusted for established clinical risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>EAT quality (as assessed via CMR T1 times), but not EAT quantity, is independently associated with a composite endpoint of nonfatal myocardial infarction, heart failure hospitalization, and all-cause death.</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":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083017","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}
Mona Sharifi, Lauren G. Fiechtner, Jessica L. Barrett, Giselle O'Connor, Meghan Perkins, Jennifer Reiner, Mandy Luo, Elsie M. Taveras, Steven L. Gortmaker
Objective
The objective of this study was to project the cost-effectiveness of implementing the Healthy Weight Clinic (HWC), a primary care-based intervention for 6- to 12-year-old children with overweight or obesity, at federally qualified health centers (FQHCs) nationally.
Methods
We estimated intervention costs from a health care sector and societal perspective and used BMI change estimates from the HWC trial. Our microsimulation of national HWC implementation among all FQHCs from 2023 to 2032 estimated cost per child and per quality-adjusted life year (QALY) gained and projected impact on obesity prevalence by race and ethnicity. Probabilistic sensitivity analyses assessed uncertainty around estimates.
Results
National implementation is projected to reach 888,000 children over 10 years, with a mean intervention cost of $456 (95% uncertainty interval [UI]: $409–$506) per child to the health care sector and $211 (95% UI: $175–$251) to families (e.g., time participating). Assuming effect maintenance, national implementation could result in 2070 (95% UI: 859–3220) QALYs gained and save $14.6 million (95% UI: $5.6–$23.5 million) in health care costs over 10 years, yielding a net cost of $278,000 (95% CI: $177,000–$679,000) per QALY gained. We project greater reductions in obesity prevalence among Hispanic/Latino and Black versus White populations.
Conclusions
The HWC is relatively low-cost per child and projected to reduce obesity disparities if implemented nationally in FQHCs.
{"title":"Cost-effectiveness of a primary care-based Healthy Weight Clinic compared with usual care","authors":"Mona Sharifi, Lauren G. Fiechtner, Jessica L. Barrett, Giselle O'Connor, Meghan Perkins, Jennifer Reiner, Mandy Luo, Elsie M. Taveras, Steven L. Gortmaker","doi":"10.1002/oby.24111","DOIUrl":"10.1002/oby.24111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to project the cost-effectiveness of implementing the Healthy Weight Clinic (HWC), a primary care-based intervention for 6- to 12-year-old children with overweight or obesity, at federally qualified health centers (FQHCs) nationally.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We estimated intervention costs from a health care sector and societal perspective and used BMI change estimates from the HWC trial. Our microsimulation of national HWC implementation among all FQHCs from 2023 to 2032 estimated cost per child and per quality-adjusted life year (QALY) gained and projected impact on obesity prevalence by race and ethnicity. Probabilistic sensitivity analyses assessed uncertainty around estimates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>National implementation is projected to reach 888,000 children over 10 years, with a mean intervention cost of $456 (95% uncertainty interval [UI]: $409–$506) per child to the health care sector and $211 (95% UI: $175–$251) to families (e.g., time participating). Assuming effect maintenance, national implementation could result in 2070 (95% UI: 859–3220) QALYs gained and save $14.6 million (95% UI: $5.6–$23.5 million) in health care costs over 10 years, yielding a net cost of $278,000 (95% CI: $177,000–$679,000) per QALY gained. We project greater reductions in obesity prevalence among Hispanic/Latino and Black versus White populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The HWC is relatively low-cost per child and projected to reduce obesity disparities if implemented nationally in FQHCs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082985","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}
Emily Benjamin Finn, Caroline V. Keller, Marissa A. Gowey, Mary Savoye, Stephanie Samuels, Abby F. Fleisch, Victoria W. Rogers, Margaret Grey, Laura J. Damschroder, Amy Beck, Mona Sharifi
Objective
The increasing prevalence of and inequities in childhood obesity demand improved access to effective treatment. The SmartMoves curriculum used in Bright Bodies, a proven-effective, intensive health behavior and lifestyle treatment (IHBLT), was disseminated to ≥30 US sites from 2003 to 2018. We aimed to identify barriers to and facilitators of IHBLT implementation/sustainment.
Methods
We surveyed and interviewed key informants about experiences acquiring/implementing SmartMoves. In parallel, we analyzed and then integrated survey findings and themes from interviews using the constant comparative method.
Results
Participants from 16 sites (53%) completed surveys, and 12 participants at 10 sites completed interviews. The 11 sites (63%) that implemented SmartMoves varied in both use of training opportunities/materials and fidelity to program components. In interviews, demand for obesity programming, organizational priorities, and partnerships facilitated implementation. Seven sites discontinued SmartMoves prior to the COVID-19 pandemic. Funding insecurity and insufficient staffing emerged as dominant barriers to implementation/sustainment discussed by all interviewees, and some also noted participants' competing demands and the program's fit with population as challenges.
Conclusions
System- and organizational-level barriers impeded sustainment of an evidence-based IHBLT program. Adequate funding could enable sufficient staffing and training to promote fidelity to the intervention's core functions and adaptation to fit local populations/context.
{"title":"Improving access to first-line treatment for pediatric obesity: Lessons from the dissemination of SmartMoves","authors":"Emily Benjamin Finn, Caroline V. Keller, Marissa A. Gowey, Mary Savoye, Stephanie Samuels, Abby F. Fleisch, Victoria W. Rogers, Margaret Grey, Laura J. Damschroder, Amy Beck, Mona Sharifi","doi":"10.1002/oby.24107","DOIUrl":"10.1002/oby.24107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The increasing prevalence of and inequities in childhood obesity demand improved access to effective treatment. The SmartMoves curriculum used in Bright Bodies, a proven-effective, intensive health behavior and lifestyle treatment (IHBLT), was disseminated to ≥30 US sites from 2003 to 2018. We aimed to identify barriers to and facilitators of IHBLT implementation/sustainment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We surveyed and interviewed key informants about experiences acquiring/implementing SmartMoves. In parallel, we analyzed and then integrated survey findings and themes from interviews using the constant comparative method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants from 16 sites (53%) completed surveys, and 12 participants at 10 sites completed interviews. The 11 sites (63%) that implemented SmartMoves varied in both use of training opportunities/materials and fidelity to program components. In interviews, demand for obesity programming, organizational priorities, and partnerships facilitated implementation. Seven sites discontinued SmartMoves prior to the COVID-19 pandemic. Funding insecurity and insufficient staffing emerged as dominant barriers to implementation/sustainment discussed by all interviewees, and some also noted participants' competing demands and the program's fit with population as challenges.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>System- and organizational-level barriers impeded sustainment of an evidence-based IHBLT program. Adequate funding could enable sufficient staffing and training to promote fidelity to the intervention's core functions and adaptation to fit local populations/context.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082987","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}
Cliona O'Donnell, Odhrán Ryan, Andrew E. Hogan, Desmond Killick, Shane Crilly, Jonathan D. Dodd, David J. Murphy, Silke Ryan, Donal O'Shea
Objective
Glucagon-like peptide-1 (GLP-1) analogues are currently the most widely used pharmacotherapies for weight loss. Their primary mechanism of action is attributed to reduction in energy intake. Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans.
Methods
Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed to evaluate VAT metabolic activity, expressed as VAT target to background ratio.
Results
Treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target to background ratio. There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss.
Conclusions
These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation.
{"title":"GLP-1 therapy increases visceral adipose tissue metabolic activity: lessons from a randomized controlled trial in obstructive sleep apnea","authors":"Cliona O'Donnell, Odhrán Ryan, Andrew E. Hogan, Desmond Killick, Shane Crilly, Jonathan D. Dodd, David J. Murphy, Silke Ryan, Donal O'Shea","doi":"10.1002/oby.24126","DOIUrl":"10.1002/oby.24126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Glucagon-like peptide-1 (GLP-1) analogues are currently the most widely used pharmacotherapies for weight loss. Their primary mechanism of action is attributed to reduction in energy intake. Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) was performed to evaluate VAT metabolic activity, expressed as VAT target to background ratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target to background ratio. There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019982","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}
We aimed to investigate the associations of changes in metabolic health across categories of body size phenotype with the risk of colorectal cancer in a community-based prospective cohort.
Methods
In the current study, a total of 70,987 participants were included. Changes in metabolic health across categories of body size phenotype were assessed between the health examination for the first time in the years 2006 through 2009 and a 2010/2011 health examination. A multivariate Cox proportional hazards model was used to assess the associations of changes in metabolic health across body size phenotype categories with risk of colorectal cancer.
Results
During the median follow-up time of 11.04 years, 428 (0.60%) participants developed colorectal cancer. Compared with metabolically healthy normal-weight (MHNW) participants who remained MH, the risk of colorectal cancer was increased by 144% (95% CI: 1.21–4.95) for participants with metabolically healthy obesity (MHO) who converted to a metabolically unhealthy (MU) phenotype. Participants who were MU at baseline were still at increased risk of colorectal cancer, regardless of obesity status.
Conclusions
The MHO phenotype was a dynamic status over time, and converting to MU during follow-up and being initially MU were associated with having an increased risk of colorectal cancer, regardless of degree of obesity and body size phenotype.
{"title":"Association between transitions in metabolic health and colorectal cancer across categories of body size phenotype: a prospective cohort study","authors":"Qian Liu, Fei Si, Yuntao Wu, Jing Yu","doi":"10.1002/oby.24122","DOIUrl":"10.1002/oby.24122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to investigate the associations of changes in metabolic health across categories of body size phenotype with the risk of colorectal cancer in a community-based prospective cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the current study, a total of 70,987 participants were included. Changes in metabolic health across categories of body size phenotype were assessed between the health examination for the first time in the years 2006 through 2009 and a 2010/2011 health examination. A multivariate Cox proportional hazards model was used to assess the associations of changes in metabolic health across body size phenotype categories with risk of colorectal cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>During the median follow-up time of 11.04 years, 428 (0.60%) participants developed colorectal cancer. Compared with metabolically healthy normal-weight (MHNW) participants who remained MH, the risk of colorectal cancer was increased by 144% (95% CI: 1.21–4.95) for participants with metabolically healthy obesity (MHO) who converted to a metabolically unhealthy (MU) phenotype. Participants who were MU at baseline were still at increased risk of colorectal cancer, regardless of obesity status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The MHO phenotype was a dynamic status over time, and converting to MU during follow-up and being initially MU were associated with having an increased risk of colorectal cancer, regardless of degree of obesity and body size phenotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019981","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}
Jami L. Josefson, Alan Kuang, Catherine Allard, Monica E. Bianco, William Lowe Jr., Denise M. Scholtens, Luigi Bouchard, Marie-France Hivert
Objective
This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity.
Methods
An epigenome-wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation. Assays were performed with Illumina EPIC arrays (791,359 CpG sites after quality control). Replication was performed in an independent cohort, Genetics of Glucose regulation in Gestation and Growth (Gen3G).
Results
In 2740 HAPO samples, significant associations were identified at 89 CpG sites after accounting for multiple testing (Bonferroni-adjusted p < 0.05). Replication analyses conducted in 139 Gen3G participants confirmed associations for seven CpG sites. These included IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds insulin-like growth factor I and insulin, and KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis; both are key regulators of growth during fetal life.
Conclusions
These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity and as potential biomarkers of metabolic disease risk.
目的：本研究旨在确定脐带血 DNA 甲基化是否与新生儿肥胖（儿童肥胖的关键风险因素）有关：本研究旨在确定脐带血DNA特定位点的甲基化是否与新生儿肥胖（儿童肥胖的关键风险因素）有关：以高血糖和不良妊娠结局（HAPO）研究为发现样本，进行了一项表观基因组关联研究。采用线性回归模型，对母体和后代协变量及细胞计数进行调整，分析新生儿脂肪含量（以三个皮褶厚度之和计）与脐带血DNA甲基化之间的关联。检测使用 Illumina EPIC 阵列（质控后有 791,359 个 CpG 位点）进行。在一个独立队列 "妊娠和生长过程中葡萄糖调节的遗传学（Genetics of Glucose regulation in Gestation and Growth，Gen3G）"中进行了复制：结果：在 2740 个 HAPO 样本中，经多重检验后发现 89 个 CpG 位点存在显著关联（Bonferroni-adjusted p 结论）：这些研究结果支持表观遗传机制在新生儿肥胖发育起源中的作用，并可作为代谢性疾病风险的潜在生物标志物。
{"title":"Newborn adiposity is associated with cord blood DNA methylation at IGF1R and KLF7","authors":"Jami L. Josefson, Alan Kuang, Catherine Allard, Monica E. Bianco, William Lowe Jr., Denise M. Scholtens, Luigi Bouchard, Marie-France Hivert","doi":"10.1002/oby.24109","DOIUrl":"10.1002/oby.24109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An epigenome-wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation. Assays were performed with Illumina EPIC arrays (791,359 CpG sites after quality control). Replication was performed in an independent cohort, Genetics of Glucose regulation in Gestation and Growth (Gen3G).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2740 HAPO samples, significant associations were identified at 89 CpG sites after accounting for multiple testing (Bonferroni-adjusted <i>p</i> < 0.05). Replication analyses conducted in 139 Gen3G participants confirmed associations for seven CpG sites. These included <i>IGF1R</i>, which encodes a transmembrane receptor involved in cell growth and survival that binds insulin-like growth factor I and insulin, and <i>KLF7</i>, which encodes a regulator of cell proliferation and inhibitor of adipogenesis; both are key regulators of growth during fetal life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity and as potential biomarkers of metabolic disease risk.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142010172","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}
Aaron Hengist, Christina M. Sciarrillo, Juen Guo, Mary Walter, Kevin D. Hall
Objective
The objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake.
Methods
A total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m2, n = 8 with normal weight, n = 6 with overweight, n = 6 with obesity) consumed a low-fat (LF) diet (10% fat, 75% carbohydrate) and a low-carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient-representative breakfast test meals, and 6-h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day.
Results
The LC meal resulted in greater mean postprandial plasma active glucagon-like peptide-1 (GLP-1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; p < 0.0001), total glucose-dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; p = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; p = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; p = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; p < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; p = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; p = 0.01) and dinner (193 [86] kcal; p = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; p < 0.0001).
Conclusions
In the short term, endogenous gut-derived appetite hormones do not necessarily determine ad libitum energy intake.
{"title":"Gut-derived appetite hormones do not explain energy intake differences in humans following low-carbohydrate versus low-fat diets","authors":"Aaron Hengist, Christina M. Sciarrillo, Juen Guo, Mary Walter, Kevin D. Hall","doi":"10.1002/oby.24104","DOIUrl":"10.1002/oby.24104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to explore how dietary macronutrient composition influences postprandial appetite hormone responses and subsequent energy intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 20 adults (mean [SEM], age 30 [1] years, BMI 27.8 [1.3] kg/m<sup>2</sup>, <i>n</i> = 8 with normal weight, <i>n</i> = 6 with overweight, <i>n</i> = 6 with obesity) consumed a low-fat (LF) diet (10% fat, 75% carbohydrate) and a low-carbohydrate (LC) diet (10% carbohydrate, 75% fat) for 2 weeks each in an inpatient randomized crossover design. At the end of each diet, participants consumed isocaloric macronutrient-representative breakfast test meals, and 6-h postprandial responses were measured. Ad libitum energy intake was measured for the rest of the day.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The LC meal resulted in greater mean postprandial plasma active glucagon-like peptide-1 (GLP-1; LC: 6.44 [0.78] pg/mL, LF: 2.46 [0.26] pg/mL; <i>p</i> < 0.0001), total glucose-dependent insulinotropic polypeptide (GIP; LC: 578 [60] pg/mL, LF: 319 [37] pg/mL; <i>p</i> = 0.0004), and peptide YY (PYY; LC: 65.6 [5.6] pg/mL, LF: 50.7 [3.8] pg/mL; <i>p</i> = 0.02), whereas total ghrelin (LC: 184 [25] pg/mL, LF: 261 [47] pg/mL; <i>p</i> = 0.0009), active ghrelin (LC: 91 [9] pg/mL, LF: 232 [28] pg/mL; <i>p</i> < 0.0001), and leptin (LC: 26.9 [6.5] ng/mL, LF: 35.2 [7.5] ng/mL; <i>p</i> = 0.01) were lower compared with LF. Participants ate more during LC at lunch (244 [85] kcal; <i>p</i> = 0.01) and dinner (193 [86] kcal; <i>p</i> = 0.04), increasing total subsequent energy intake for the day compared with LF (551 [103] kcal; <i>p</i> < 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In the short term, endogenous gut-derived appetite hormones do not necessarily determine ad libitum energy intake.</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":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904069","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}
Taylor Neuman, Richele Corrado, Amanda Banaag, Tracey Perez Koehlmoos
Objective
The prevalence of overweight and obesity among beneficiaries of the Military Health System (MHS) is 41.6% and 30.5%, respectively. This incurs significant medical, fiscal, and military readiness costs. It is not currently known how the utilization of antiobesity medications (AOMs) within the MHS compares with that in the Veterans Health Administration or the private sector. Our aim was to assess the utilization of AOMs within the MHS.
Methods
A cross-sectional study was conducted using data gathered from the MHS Data Repository and the inclusion of all adult TRICARE Prime and Plus beneficiaries ages 18 to 64 years who were prescribed at least one TRICARE-approved AOM during the years 2018 to 2022.
Results
The total study population included 4,414,127 beneficiaries, of whom 1,871,780 were active-duty service members. The utilization of AOMs among the eligible population was 0.56% (0.44% among active-duty personnel). Liraglutide was the most-prescribed AOM (36% of the total). Female sex, age greater than or equal to 30 but less than 60 years, and enlisted or warrant officer rank were all associated with statistically significant higher odds of receiving AOMs.
Conclusions
Comparable with the US private sector, the MHS significantly underutilizes AOMs, including among active-duty service members, despite coverage of AOMs since 2018.
{"title":"Utilization of antiobesity medications within the Military Health System","authors":"Taylor Neuman, Richele Corrado, Amanda Banaag, Tracey Perez Koehlmoos","doi":"10.1002/oby.24097","DOIUrl":"10.1002/oby.24097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The prevalence of overweight and obesity among beneficiaries of the Military Health System (MHS) is 41.6% and 30.5%, respectively. This incurs significant medical, fiscal, and military readiness costs. It is not currently known how the utilization of antiobesity medications (AOMs) within the MHS compares with that in the Veterans Health Administration or the private sector. Our aim was to assess the utilization of AOMs within the MHS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cross-sectional study was conducted using data gathered from the MHS Data Repository and the inclusion of all adult TRICARE Prime and Plus beneficiaries ages 18 to 64 years who were prescribed at least one TRICARE-approved AOM during the years 2018 to 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The total study population included 4,414,127 beneficiaries, of whom 1,871,780 were active-duty service members. The utilization of AOMs among the eligible population was 0.56% (0.44% among active-duty personnel). Liraglutide was the most-prescribed AOM (36% of the total). Female sex, age greater than or equal to 30 but less than 60 years, and enlisted or warrant officer rank were all associated with statistically significant higher odds of receiving AOMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Comparable with the US private sector, the MHS significantly underutilizes AOMs, including among active-duty service members, despite coverage of AOMs since 2018.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.24097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877059","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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