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Pediatric obesity and the risk of multiple sclerosis: a nationwide prospective cohort study.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-30 DOI: 10.1038/s41366-025-01727-3
Emilia Hagman, Resthie R Putri, Pernilla Danielsson, Claude Marcus

Background: Emerging evidence implies a link between high pediatric body mass index (BMI) and an increased risk of multiple sclerosis (MS). However, previous research suggests this association is only present for adolescent obesity and not childhood obesity. The present study aimed to assess the association between pediatric obesity and risk of developing MS, and to investigate if degree of obesity and age at obesity treatment initiation affects the risk. In a subgroup, response to obesity treatment on MS risk was assessed.

Methods: In this cohort study, patients aged 2-19 years from the Swedish Childhood Obesity Treatment Register (BORIS), and matched individuals from the general population were followed prospectively. MS was identified through the National Patient Register. Hazard ratios (HR) adjusted for parental MS were calculated.

Results: The study included 21,652 individuals with pediatric obesity and 102,187 general population comparators. The median age at follow-up was 21 (Q1, Q3 18, 25) years. The adjusted HR (95% CI) for developing MS in the pediatric obesity cohort was 2.28 (1.45-3.58). In stratified analyses, obesity class I was not associated with MS, HR = 1.34 (0.64-2.81), while the association between obesity class II and MS was strengthened, HR = 3.42 (1.89-6.19). MS was associated with both childhood obesity, HR = 3.16 (1.12-8.87), and adolescent obesity, HR = 2.12 (1.28-3.51). A decrease in BMI SDS was not associated with lower likelihood of MS, HR = 1.09 (0.92-1.29) per 0.25 BMI SDS unit decrease.

Conclusions: Both childhood and adolescent obesity are associated with an increased risk of MS. Moreover, a dose-response relationship between the degree of obesity and the risk of future MS was indicated, while response to pediatric obesity treatment did not affect the association, highlighting the importance of preventing high degree of obesity early in life.

{"title":"Pediatric obesity and the risk of multiple sclerosis: a nationwide prospective cohort study.","authors":"Emilia Hagman, Resthie R Putri, Pernilla Danielsson, Claude Marcus","doi":"10.1038/s41366-025-01727-3","DOIUrl":"https://doi.org/10.1038/s41366-025-01727-3","url":null,"abstract":"<p><strong>Background: </strong>Emerging evidence implies a link between high pediatric body mass index (BMI) and an increased risk of multiple sclerosis (MS). However, previous research suggests this association is only present for adolescent obesity and not childhood obesity. The present study aimed to assess the association between pediatric obesity and risk of developing MS, and to investigate if degree of obesity and age at obesity treatment initiation affects the risk. In a subgroup, response to obesity treatment on MS risk was assessed.</p><p><strong>Methods: </strong>In this cohort study, patients aged 2-19 years from the Swedish Childhood Obesity Treatment Register (BORIS), and matched individuals from the general population were followed prospectively. MS was identified through the National Patient Register. Hazard ratios (HR) adjusted for parental MS were calculated.</p><p><strong>Results: </strong>The study included 21,652 individuals with pediatric obesity and 102,187 general population comparators. The median age at follow-up was 21 (Q1, Q3 18, 25) years. The adjusted HR (95% CI) for developing MS in the pediatric obesity cohort was 2.28 (1.45-3.58). In stratified analyses, obesity class I was not associated with MS, HR = 1.34 (0.64-2.81), while the association between obesity class II and MS was strengthened, HR = 3.42 (1.89-6.19). MS was associated with both childhood obesity, HR = 3.16 (1.12-8.87), and adolescent obesity, HR = 2.12 (1.28-3.51). A decrease in BMI SDS was not associated with lower likelihood of MS, HR = 1.09 (0.92-1.29) per 0.25 BMI SDS unit decrease.</p><p><strong>Conclusions: </strong>Both childhood and adolescent obesity are associated with an increased risk of MS. Moreover, a dose-response relationship between the degree of obesity and the risk of future MS was indicated, while response to pediatric obesity treatment did not affect the association, highlighting the importance of preventing high degree of obesity early in life.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065510","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}
引用次数: 0
Intramyocellular lipid use is altered with exercise in males with childhood-onset obesity despite no differences in substrate oxidation.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-29 DOI: 10.1038/s41366-025-01720-w
S Feola, L Al-Nabelsi, B T Tam, J Near, J A Morais, S Santosa

Objective: Compared to adulthood-onset obesity (AO), those with childhood-onset obesity (CO) are at greater risk of metabolic disease. However, the differences between these two obesity phenotypes are not clear. The aim of this study is to investigate how the age of obesity onset (CO vs. AO) affects the use of intramyocellular (IMCL) and extramyocellular (EMCL) lipids in response to exercise.

Methods: Males with CO (n = 5) and AO (n = 5) were recruited. At the first study visit, body composition was measured via dual-energy x-ray absorptiometry (DEXA). Energy expenditure and substrate oxidation were measured via indirect calorimetry. Participants were provided with standardized meals for 3 days prior to the exercise study visit. At the exercise study visit, IMCL and EMCL were measured via magnetic resonance spectroscopy (MRS) before and after 90-minutes of moderate intensity cycling with indirect calorimetry.

Results: Substrate oxidation at rest and during exercise was not different between groups. Post-exercise, a decrease in IMCL was observed in the AO group that was not demonstrated in the CO group. There were no changes in EMCL post-exercise in either group.

Conclusions: This was the first study to compare the effects of exercise on IMCL and EMCL use in males with CO and AO. The decreases in IMCL of the AO group is similar with those observed in the literature in lean individuals. We made the novel observation that with moderate intensity cycling, males with CO do not appear to use IMCL as effectively as those with AO, suggesting perturbations in IMCL metabolism.

{"title":"Intramyocellular lipid use is altered with exercise in males with childhood-onset obesity despite no differences in substrate oxidation.","authors":"S Feola, L Al-Nabelsi, B T Tam, J Near, J A Morais, S Santosa","doi":"10.1038/s41366-025-01720-w","DOIUrl":"https://doi.org/10.1038/s41366-025-01720-w","url":null,"abstract":"<p><strong>Objective: </strong>Compared to adulthood-onset obesity (AO), those with childhood-onset obesity (CO) are at greater risk of metabolic disease. However, the differences between these two obesity phenotypes are not clear. The aim of this study is to investigate how the age of obesity onset (CO vs. AO) affects the use of intramyocellular (IMCL) and extramyocellular (EMCL) lipids in response to exercise.</p><p><strong>Methods: </strong>Males with CO (n = 5) and AO (n = 5) were recruited. At the first study visit, body composition was measured via dual-energy x-ray absorptiometry (DEXA). Energy expenditure and substrate oxidation were measured via indirect calorimetry. Participants were provided with standardized meals for 3 days prior to the exercise study visit. At the exercise study visit, IMCL and EMCL were measured via magnetic resonance spectroscopy (MRS) before and after 90-minutes of moderate intensity cycling with indirect calorimetry.</p><p><strong>Results: </strong>Substrate oxidation at rest and during exercise was not different between groups. Post-exercise, a decrease in IMCL was observed in the AO group that was not demonstrated in the CO group. There were no changes in EMCL post-exercise in either group.</p><p><strong>Conclusions: </strong>This was the first study to compare the effects of exercise on IMCL and EMCL use in males with CO and AO. The decreases in IMCL of the AO group is similar with those observed in the literature in lean individuals. We made the novel observation that with moderate intensity cycling, males with CO do not appear to use IMCL as effectively as those with AO, suggesting perturbations in IMCL metabolism.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058936","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}
引用次数: 0
Editorial on obesity: a 100-year journey—the past, present and future
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-29 DOI: 10.1038/s41366-025-01722-8
Jennifer L. Baker
{"title":"Editorial on obesity: a 100-year journey—the past, present and future","authors":"Jennifer L. Baker","doi":"10.1038/s41366-025-01722-8","DOIUrl":"10.1038/s41366-025-01722-8","url":null,"abstract":"","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":"49 2","pages":"157-158"},"PeriodicalIF":4.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41366-025-01722-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065508","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}
引用次数: 0
Association of BCHE gene SNP rs1803274 (K-variant) and rs3495 with obesity in Pakistani population group.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-28 DOI: 10.1038/s41366-025-01715-7
Amna Amir, Sabir Hussain, Syed Tahir Abbas Shah, Rabia Habib, Zahid Muneer, Eugenie Nepovimova, Kamil Kuca, Syed Muhammad Nurulain

Background: Obesity plays a crucial role in the development of metabolic disorders including diabetes, coronary and renal diseases. There are several factors involved in the pathology of obesity, including chronic inflammation and exposure to environmental contaminants. Recently, the cholinergic co-hydrolyzing enzyme BChE has been associated with clinical conditions such as diabetes and obesity. This study aims to investigate the levels of BChE and inflammatory markers in the serum, as well as the association between two specific BCHE gene variants (rs1803274 and rs3495) and the risk of obesity in the Pakistani population.

Methods: The study recruited 350 people with obesity and 200 volunteers with no obesity. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) levels were quantified using ELISA kits, while the analysis of BCHE gene SNPs rs1803274 (K-variant) and rs3495 was conducted using the tetra-primer amplification refractory mutation-PCR (tetra-ARM-PCR) and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. Additionally, clinico-pathological parameters HDL, LDL, BMI, Homa-IR, insulin, glucose, blood pressure was also assessed in subjects of current study.

Results: Results showed significantly higher levels of BChE, TNF-α, IL-1β, and IL-6 in the obesity group compared to the group without obesity. Furthermore, the obesity group exhibited higher blood pressure and LDL levels, as well as lower HDL levels when compared to group without obesity. Logistic regression analysis revealed a relationship between obesity and higher BChE activity, blood pressure, LDL, and lower HDL levels. The study also found a statistically significant association between the BCHE gene SNPs rs1803274 (K-variant) and rs3495 and the risk of obesity (OR = 2.01; CI = 1.21-3.33; p = 0.0063; OR = 1.80; CI = 1.09-2.96, respectively).

Conclusions: In conclusion, the study suggests that BChE and inflammatory cytokines play a significant role in the development and pathogenesis of obesity and can also act as good diagnostic biomarkers for obesity and its related metabolic disorders.

{"title":"Association of BCHE gene SNP rs1803274 (K-variant) and rs3495 with obesity in Pakistani population group.","authors":"Amna Amir, Sabir Hussain, Syed Tahir Abbas Shah, Rabia Habib, Zahid Muneer, Eugenie Nepovimova, Kamil Kuca, Syed Muhammad Nurulain","doi":"10.1038/s41366-025-01715-7","DOIUrl":"https://doi.org/10.1038/s41366-025-01715-7","url":null,"abstract":"<p><strong>Background: </strong>Obesity plays a crucial role in the development of metabolic disorders including diabetes, coronary and renal diseases. There are several factors involved in the pathology of obesity, including chronic inflammation and exposure to environmental contaminants. Recently, the cholinergic co-hydrolyzing enzyme BChE has been associated with clinical conditions such as diabetes and obesity. This study aims to investigate the levels of BChE and inflammatory markers in the serum, as well as the association between two specific BCHE gene variants (rs1803274 and rs3495) and the risk of obesity in the Pakistani population.</p><p><strong>Methods: </strong>The study recruited 350 people with obesity and 200 volunteers with no obesity. Proinflammatory cytokines (TNF-α, IL-6, and IL-1β) levels were quantified using ELISA kits, while the analysis of BCHE gene SNPs rs1803274 (K-variant) and rs3495 was conducted using the tetra-primer amplification refractory mutation-PCR (tetra-ARM-PCR) and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. Additionally, clinico-pathological parameters HDL, LDL, BMI, Homa-IR, insulin, glucose, blood pressure was also assessed in subjects of current study.</p><p><strong>Results: </strong>Results showed significantly higher levels of BChE, TNF-α, IL-1β, and IL-6 in the obesity group compared to the group without obesity. Furthermore, the obesity group exhibited higher blood pressure and LDL levels, as well as lower HDL levels when compared to group without obesity. Logistic regression analysis revealed a relationship between obesity and higher BChE activity, blood pressure, LDL, and lower HDL levels. The study also found a statistically significant association between the BCHE gene SNPs rs1803274 (K-variant) and rs3495 and the risk of obesity (OR = 2.01; CI = 1.21-3.33; p = 0.0063; OR = 1.80; CI = 1.09-2.96, respectively).</p><p><strong>Conclusions: </strong>In conclusion, the study suggests that BChE and inflammatory cytokines play a significant role in the development and pathogenesis of obesity and can also act as good diagnostic biomarkers for obesity and its related metabolic disorders.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058933","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}
引用次数: 0
Who drives weight stigma? A multinational exploration of clustering characteristics behind weight bias against preconception, pregnant, and postpartum women.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-28 DOI: 10.1038/s41366-025-01725-5
Haimanot Hailu, Angela C Incollingo Rodriguez, Anthony Rodriguez, Helen Skouteris, Briony Hill

Background: Weight bias is a global health challenge and community members are endorsed as the most common source of weight bias. The nature of weight biases specifically against preconception, pregnant, and postpartum (PPP) women from the perspective of community members is not known, especially in terms of cross-cultural trends. We investigated the magnitude of explicit and implicit weight bias and profiles of characteristics associated with harbouring weight bias.

Methods: We conducted a multinational investigation of clusters of factors associated with weight bias against PPP women (May-July 2023). Community members from Australia, Canada, United States (US), United Kingdom (UK), Malaysia, and India completed a cross-sectional survey measuring explicit and implicit weight biases, beliefs about weight controllability, and awareness of sociocultural body ideals. Hierarchical multiple regression and latent profile analyses identified clusters of factors associated with weight bias.

Results: Participants from India reported the lowest explicit weight bias (B = -0.45, p = 0.02). Participants from Australia (B = -0.14, p = 0.04) and the UK (B = -0.16, p = 0.02) (vs. US) reported the lowest implicit weight bias. Three distinct profiles were identified clustering on body mass index (BMI) and weight-controllability beliefs: low-BMI/moderate-beliefs, high-BMI/more biased beliefs, and high-BMI/less biased beliefs. Profile membership varied by country of residence and weight bias outcomes with low-BMI/moderate-beliefs profiles containing more people from non-Western countries and with low explicit weight bias.

Conclusions: Explicit and implicit weight bias was harboured by participants across all included nations, although less pronounced in non-Western countries. Our profiles highlight that individuals who held a stronger belief that weight is controllable, regardless of their body weight, should be targeted for interventions to eliminate weight stigma.

{"title":"Who drives weight stigma? A multinational exploration of clustering characteristics behind weight bias against preconception, pregnant, and postpartum women.","authors":"Haimanot Hailu, Angela C Incollingo Rodriguez, Anthony Rodriguez, Helen Skouteris, Briony Hill","doi":"10.1038/s41366-025-01725-5","DOIUrl":"10.1038/s41366-025-01725-5","url":null,"abstract":"<p><strong>Background: </strong>Weight bias is a global health challenge and community members are endorsed as the most common source of weight bias. The nature of weight biases specifically against preconception, pregnant, and postpartum (PPP) women from the perspective of community members is not known, especially in terms of cross-cultural trends. We investigated the magnitude of explicit and implicit weight bias and profiles of characteristics associated with harbouring weight bias.</p><p><strong>Methods: </strong>We conducted a multinational investigation of clusters of factors associated with weight bias against PPP women (May-July 2023). Community members from Australia, Canada, United States (US), United Kingdom (UK), Malaysia, and India completed a cross-sectional survey measuring explicit and implicit weight biases, beliefs about weight controllability, and awareness of sociocultural body ideals. Hierarchical multiple regression and latent profile analyses identified clusters of factors associated with weight bias.</p><p><strong>Results: </strong>Participants from India reported the lowest explicit weight bias (B = -0.45, p = 0.02). Participants from Australia (B = -0.14, p = 0.04) and the UK (B = -0.16, p = 0.02) (vs. US) reported the lowest implicit weight bias. Three distinct profiles were identified clustering on body mass index (BMI) and weight-controllability beliefs: low-BMI/moderate-beliefs, high-BMI/more biased beliefs, and high-BMI/less biased beliefs. Profile membership varied by country of residence and weight bias outcomes with low-BMI/moderate-beliefs profiles containing more people from non-Western countries and with low explicit weight bias.</p><p><strong>Conclusions: </strong>Explicit and implicit weight bias was harboured by participants across all included nations, although less pronounced in non-Western countries. Our profiles highlight that individuals who held a stronger belief that weight is controllable, regardless of their body weight, should be targeted for interventions to eliminate weight stigma.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058940","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}
引用次数: 0
Assessing online chat-based artificial intelligence models for weight loss recommendation appropriateness and bias in the presence of guideline incongruence.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-27 DOI: 10.1038/s41366-025-01717-5
Eugene Annor, Joseph Atarere, Nneoma Ubah, Oladoyin Jolaoye, Bryce Kunkle, Olachi Egbo, Daniel K Martin

Background and aim: Managing obesity requires a comprehensive approach that involves therapeutic lifestyle changes, medications, or metabolic surgery. Many patients seek health information from online sources and artificial intelligence models like ChatGPT, Google Gemini, and Microsoft Copilot before consulting health professionals. This study aims to evaluate the appropriateness of the responses of Google Gemini and Microsoft Copilot to questions on pharmacologic and surgical management of obesity and assess for bias in their responses to either the ADA or AACE guidelines.

Methods: Ten questions were compiled into a set and posed separately to the free editions of Google Gemini and Microsoft Copilot. Recommendations for the questions were extracted from the ADA and the AACE websites, and the responses were graded by reviewers for appropriateness, completeness, and bias to any of the guidelines.

Results: All responses from Microsoft Copilot and 8/10 (80%) responses from Google Gemini were appropriate. There were no inappropriate responses. Google Gemini refused to respond to two questions and insisted on consulting a physician. Microsoft Copilot (10/10; 100%) provided a higher proportion of complete responses than Google Gemini (5/10; 50%). Of the eight responses from Google Gemini, none were biased towards any of the guidelines, while two of the responses from Microsoft Copilot were biased.

Conclusion: The study highlights the role of Microsoft Copilot and Google Gemini in weight loss management. The differences in their responses may be attributed to the variation in the quality and scope of their training data and design.

{"title":"Assessing online chat-based artificial intelligence models for weight loss recommendation appropriateness and bias in the presence of guideline incongruence.","authors":"Eugene Annor, Joseph Atarere, Nneoma Ubah, Oladoyin Jolaoye, Bryce Kunkle, Olachi Egbo, Daniel K Martin","doi":"10.1038/s41366-025-01717-5","DOIUrl":"https://doi.org/10.1038/s41366-025-01717-5","url":null,"abstract":"<p><strong>Background and aim: </strong>Managing obesity requires a comprehensive approach that involves therapeutic lifestyle changes, medications, or metabolic surgery. Many patients seek health information from online sources and artificial intelligence models like ChatGPT, Google Gemini, and Microsoft Copilot before consulting health professionals. This study aims to evaluate the appropriateness of the responses of Google Gemini and Microsoft Copilot to questions on pharmacologic and surgical management of obesity and assess for bias in their responses to either the ADA or AACE guidelines.</p><p><strong>Methods: </strong>Ten questions were compiled into a set and posed separately to the free editions of Google Gemini and Microsoft Copilot. Recommendations for the questions were extracted from the ADA and the AACE websites, and the responses were graded by reviewers for appropriateness, completeness, and bias to any of the guidelines.</p><p><strong>Results: </strong>All responses from Microsoft Copilot and 8/10 (80%) responses from Google Gemini were appropriate. There were no inappropriate responses. Google Gemini refused to respond to two questions and insisted on consulting a physician. Microsoft Copilot (10/10; 100%) provided a higher proportion of complete responses than Google Gemini (5/10; 50%). Of the eight responses from Google Gemini, none were biased towards any of the guidelines, while two of the responses from Microsoft Copilot were biased.</p><p><strong>Conclusion: </strong>The study highlights the role of Microsoft Copilot and Google Gemini in weight loss management. The differences in their responses may be attributed to the variation in the quality and scope of their training data and design.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052574","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}
引用次数: 0
Association of long-term weight management pharmacotherapy with multiple health outcomes: an umbrella review and evidence map.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-26 DOI: 10.1038/s41366-025-01719-3
Ting-Ting Lu, Bin Liu, Long Ge, Ya-Li Liu, Yu Lu

Background: Multiple meta-analyses (MAs) have demonstrated that six pharmacotherapies, including orlistat, liraglutide, phentermine/topiramate, naltrexone/bupropion, semaglutide, and tirzepatide, improve weight loss and weight maintenance. However, few studies have synthesized and evaluated the quality of this evidence.

Objective: To identify the relevant MAs of randomized clinical trials (RCTs) that explored the association between the six pharmacotherapies and obesity-related health outcomes and adverse events (AEs).

Methods: A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from database inception up to January 2024. We calculated the effect size as the mean difference and risk ratio using the random-effects model. The quality of MAs was evaluated using "A Measurement Tool to Assess Systematic Reviews 2".

Results: Sixteen MAs comprising 235 RCTs that described 115 unique associations between the six pharmacotherapies and various health outcomes were included. Overall, 101 statistically significant associations (88%) had beneficial outcomes on body weight, weight loss, waist circumference, body mass index, total cholesterol, triglycerides, both low-density and high-density lipoprotein cholesterol, blood pressure, and glycemic profile. The pharmacotherapies were associated with significant weight loss and partial improvements in the lipid profile, blood pressure, and glycemic control among individuals with overweight or obesity. Notable AEs were associated with liraglutide, naltrexone/bupropion, semaglutide, and orlistat. The methodological quality of the included MAs requires improvement.

Conclusions: This umbrella review identified significant beneficial associations between pharmacotherapies and anthropometric measures, lipid profile, blood pressure, glycemic profile, and quality-of-life outcomes in individuals with overweight or obesity. In addition, the umbrella review highlighted safety considerations. The findings affirm the efficacy of the six pharmacotherapies in promoting weight loss in this demographic. Further clinical trials with long-term follow-up are essential to evaluate the effects of these pharmacotherapies on clinical outcomes, including cancer, cardiovascular events, and mortality.

{"title":"Association of long-term weight management pharmacotherapy with multiple health outcomes: an umbrella review and evidence map.","authors":"Ting-Ting Lu, Bin Liu, Long Ge, Ya-Li Liu, Yu Lu","doi":"10.1038/s41366-025-01719-3","DOIUrl":"https://doi.org/10.1038/s41366-025-01719-3","url":null,"abstract":"<p><strong>Background: </strong>Multiple meta-analyses (MAs) have demonstrated that six pharmacotherapies, including orlistat, liraglutide, phentermine/topiramate, naltrexone/bupropion, semaglutide, and tirzepatide, improve weight loss and weight maintenance. However, few studies have synthesized and evaluated the quality of this evidence.</p><p><strong>Objective: </strong>To identify the relevant MAs of randomized clinical trials (RCTs) that explored the association between the six pharmacotherapies and obesity-related health outcomes and adverse events (AEs).</p><p><strong>Methods: </strong>A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Web of Science from database inception up to January 2024. We calculated the effect size as the mean difference and risk ratio using the random-effects model. The quality of MAs was evaluated using \"A Measurement Tool to Assess Systematic Reviews 2\".</p><p><strong>Results: </strong>Sixteen MAs comprising 235 RCTs that described 115 unique associations between the six pharmacotherapies and various health outcomes were included. Overall, 101 statistically significant associations (88%) had beneficial outcomes on body weight, weight loss, waist circumference, body mass index, total cholesterol, triglycerides, both low-density and high-density lipoprotein cholesterol, blood pressure, and glycemic profile. The pharmacotherapies were associated with significant weight loss and partial improvements in the lipid profile, blood pressure, and glycemic control among individuals with overweight or obesity. Notable AEs were associated with liraglutide, naltrexone/bupropion, semaglutide, and orlistat. The methodological quality of the included MAs requires improvement.</p><p><strong>Conclusions: </strong>This umbrella review identified significant beneficial associations between pharmacotherapies and anthropometric measures, lipid profile, blood pressure, glycemic profile, and quality-of-life outcomes in individuals with overweight or obesity. In addition, the umbrella review highlighted safety considerations. The findings affirm the efficacy of the six pharmacotherapies in promoting weight loss in this demographic. Further clinical trials with long-term follow-up are essential to evaluate the effects of these pharmacotherapies on clinical outcomes, including cancer, cardiovascular events, and mortality.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046692","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}
引用次数: 0
Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-26 DOI: 10.1038/s41366-025-01716-6
Yusuke Miura, Satoshi Higuchi, Takashi Kohno, Yasuyuki Shiraishi, Mitsunobu Kitamura, Yuji Nagatomo, Yumiko Kawakubo Ichihara, Atsushi Mizuno, Shintaro Nakano, Kyoko Soejima, Ayumi Goda, Shun Kohsaka, Tsutomu Yoshikawa

Background: Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia.

Methods: A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m2, 20-25 kg/m2, and ≥25 kg/m2, respectively. Cachexia was defined as a combination of BMI < 20 kg/m2 and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated.

Results: This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m2 [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90-0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30-2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34-2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61-8.08; p = 0.002).

Conclusions: BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.

{"title":"Cachectic biomarkers as confounders behind the obesity paradox in patients with acute decompensated heart failure.","authors":"Yusuke Miura, Satoshi Higuchi, Takashi Kohno, Yasuyuki Shiraishi, Mitsunobu Kitamura, Yuji Nagatomo, Yumiko Kawakubo Ichihara, Atsushi Mizuno, Shintaro Nakano, Kyoko Soejima, Ayumi Goda, Shun Kohsaka, Tsutomu Yoshikawa","doi":"10.1038/s41366-025-01716-6","DOIUrl":"10.1038/s41366-025-01716-6","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a risk factor for heart failure (HF) development but is associated with a lower incidence of mortality in HF patients. This obesity paradox may be confounded by unrecognized comorbidities, including cachexia.</p><p><strong>Methods: </strong>A retrospective assessment was conducted using data from a prospectively recruiting multicenter registry, which included consecutive acute heart failure patients. A low, normal, and high body mass index (BMI) was defined as <20 kg/m<sup>2</sup>, 20-25 kg/m<sup>2</sup>, and ≥25 kg/m<sup>2</sup>, respectively. Cachexia was defined as a combination of BMI < 20 kg/m<sup>2</sup> and any biochemical abnormalities including albumin, hemoglobin, or C-reactive protein. Patients with either of the three biochemical abnormalities were categorized as those with cachectic biomarkers. Two-year all-cause, cardiac, and noncardiac mortality were evaluated.</p><p><strong>Results: </strong>This study evaluated 3314 patients (mean BMI, 22 ± 4 kg/m<sup>2</sup> [low BMI with cachexia, 828 (25%); low BMI without cachexia, 273 (8%); normal BMI, 1584 (48%); high BMI, 629 (19%)]). Overall, an increase of 1 point in BMI was associated with a decreased incidence of all-cause mortality (adjusted hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.90-0.94; p < 0.001). Regardless of the mode of death, the low BMI with cachexia indicated the worst prognosis, while the low BMI without cachexia showed a similar prognosis to the normal BMI. Cachectic biomarkers, which were observed more frequently in the low BMI, predicted a higher incidence of 2-year all-cause mortality across the BMI categories (adjusted HR for the low BMI, 1.90; 95% CI, 1.30-2.77; p = 0.001; adjusted HR for the normal BMI, 1.94; 95% CI, 1.34-2.79; p < 0.001; adjusted HR for the high BMI, 3.60; 95% CI, 1.61-8.08; p = 0.002).</p><p><strong>Conclusions: </strong>BMI could be only a surrogate marker. The cachectic biomarkers may reflect the underlying conditions and contribute to elucidating the obesity paradox.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038846","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}
引用次数: 0
Association of novel metabolic status with asymptomatic intracranial arterial stenosis: A cross-sectional study.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-25 DOI: 10.1038/s41366-025-01723-7
Liying Guo, Yongli Pan, Yumeng Yang, Xianglong Kong, Shiqing Song, Maoyu Li, Yuanyuan Zhao, Xiaotong Ma, Xiang Wang, Qinjian Sun

Objectives: To investigate the association of metabolic status newly defined or obesity with asymptomatic intracranial arterial stenosis (aICAS) among populations in rural China.

Methods: The cross-sectional study is based on the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) cohort, which enrolled 2005 participants aged 40 years or older without a history of clinical stroke or transient ischemic attack. Metabolically healthy status (MH) was defined by a newly proposed criterion: (1) systolic blood pressure (SBP) < 130 mmHg and without antihypertensive medication; (2) a waist-to-hip ratio (WHR) below 1.03 for men and below 0.95 for women; (3) no diabetes. All participants were categorized based on their metabolic status and obesity. Multivariate logistic regression models were used to investigate the association between metabolic status or obesity and aICAS.

Results: Among 2005 participants, 1597 (79.65%) were defined as metabolically unhealthy status (MU) according to the new criterion. MU was significantly associated with aICAS (OR 2.02, 95% CI 1.11-3.68, P = 0.021), especially moderate-to-severe aICAS (OR 2.43, 95% CI 1.04-5.72, P = 0.042). The prevalence of aICAS increased with the numbers of metabolic disorders (P for linear trend <0.001). Both metabolically unhealthy normal-weight (MUN) (OR 2.11, 95% CI 1.10-4.03, P = 0.025) and metabolically unhealthy obesity (MUO) (OR 3.30, 95% CI 1.64-6.64, P = 0.001) were significantly correlated with aICAS, but not metabolically healthy obesity (MHO). Subgroup analysis further confirmed the association between MU and aICAS risk only in men (P for interaction = 0.042).

Conclusions: MU defined by the new criterion was significantly associated with aICAS, especially with moderate-to-severe aICAS. This novel criterion effectively identifies individuals with a high prevalence of aICAS among populations with obesity, which could be crucial for stroke prevention.

{"title":"Association of novel metabolic status with asymptomatic intracranial arterial stenosis: A cross-sectional study.","authors":"Liying Guo, Yongli Pan, Yumeng Yang, Xianglong Kong, Shiqing Song, Maoyu Li, Yuanyuan Zhao, Xiaotong Ma, Xiang Wang, Qinjian Sun","doi":"10.1038/s41366-025-01723-7","DOIUrl":"https://doi.org/10.1038/s41366-025-01723-7","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association of metabolic status newly defined or obesity with asymptomatic intracranial arterial stenosis (aICAS) among populations in rural China.</p><p><strong>Methods: </strong>The cross-sectional study is based on the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) cohort, which enrolled 2005 participants aged 40 years or older without a history of clinical stroke or transient ischemic attack. Metabolically healthy status (MH) was defined by a newly proposed criterion: (1) systolic blood pressure (SBP) < 130 mmHg and without antihypertensive medication; (2) a waist-to-hip ratio (WHR) below 1.03 for men and below 0.95 for women; (3) no diabetes. All participants were categorized based on their metabolic status and obesity. Multivariate logistic regression models were used to investigate the association between metabolic status or obesity and aICAS.</p><p><strong>Results: </strong>Among 2005 participants, 1597 (79.65%) were defined as metabolically unhealthy status (MU) according to the new criterion. MU was significantly associated with aICAS (OR 2.02, 95% CI 1.11-3.68, P = 0.021), especially moderate-to-severe aICAS (OR 2.43, 95% CI 1.04-5.72, P = 0.042). The prevalence of aICAS increased with the numbers of metabolic disorders (P for linear trend <0.001). Both metabolically unhealthy normal-weight (MUN) (OR 2.11, 95% CI 1.10-4.03, P = 0.025) and metabolically unhealthy obesity (MUO) (OR 3.30, 95% CI 1.64-6.64, P = 0.001) were significantly correlated with aICAS, but not metabolically healthy obesity (MHO). Subgroup analysis further confirmed the association between MU and aICAS risk only in men (P for interaction = 0.042).</p><p><strong>Conclusions: </strong>MU defined by the new criterion was significantly associated with aICAS, especially with moderate-to-severe aICAS. This novel criterion effectively identifies individuals with a high prevalence of aICAS among populations with obesity, which could be crucial for stroke prevention.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038833","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}
引用次数: 0
Curcumin enhances the anti-obesogenic activity of orlistat through SKN-1/NRF2-dependent regulation of nutrient metabolism in Caenorhabditis elegans.
IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-01-24 DOI: 10.1038/s41366-025-01724-6
Martina S Savova, Monika N Todorova, Biser K Binev, Milen I Georgiev, Liliya V Mihaylova

Background: Metabolic dysregulation, a defining feature of obesity, disrupts essential signalling pathways involved in nutrient sensing and mitochondria homeostasis. The nuclear factor erythroid 2-related factor 2 (NRF-2) serves as a pivotal regulator of the cellular stress response, and recent studies have implicated it in the pathogenesis of obesity, diabetes, and metabolic syndrome. Curcumin, a polyphenolic compound derived from turmeric, has been identified as a potent activator of NRF-2. Evidence suggests curcumin impacts obesity and metabolic disorders by modulating gut microbiota composition, increasing energy expenditure, and regulating lipid metabolism. Orlistat, an anti-obesity drug, inhibits fat absorption in the gastrointestinal tract, but its side effects limits its broader use.

Objectives: The present study aims to investigate the potential synergetic effect of a hybrid combination between orlistat and curcumin. Additionally, we provide a detailed understanding of the molecular mechanisms through which this combination mitigates glucose-induced lipid accumulation in Caenorhabditis elegans, with a focus on the role of the skinhead 1 (SKN-1) transcription factor, an orthologue of NRF2.

Methods: We assessed the lipid accumulation and the changes in skn-1 transcriptional activity in C. elegans using confocal GFP-based detection, alongside mRNA expression analysis of genes from lipid metabolism and oxidative stress response in wild-type, QV225 and LD1 strains. Furthermore, we evaluated locomotion, chemotaxis and mitochondrial dynamics to enhance our understanding of the proposed molecular-based model.

Results: Our findings reveal that the orlistat/curcumin combination exerts an anti-obesogenic effect through SKN-1/NRF2-dependent regulation of conserved genes involved in carbohydrate and lipid metabolism in C. elegans. Moreover, the combination stimulates mitochondrial potential, further contributing to the observed synergistic effects.

Conclusion: The hybrid combination of orlistat and curcumin demonstrates significant anti-obesity activity by regulating nutrient-sensing pathways through SKN-1/NRF-2 modulation. This approach may allow for the reduction of orlistat dosage, thereby minimizing its adverse effects while maintaining its therapeutic efficacy.

{"title":"Curcumin enhances the anti-obesogenic activity of orlistat through SKN-1/NRF2-dependent regulation of nutrient metabolism in Caenorhabditis elegans.","authors":"Martina S Savova, Monika N Todorova, Biser K Binev, Milen I Georgiev, Liliya V Mihaylova","doi":"10.1038/s41366-025-01724-6","DOIUrl":"https://doi.org/10.1038/s41366-025-01724-6","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysregulation, a defining feature of obesity, disrupts essential signalling pathways involved in nutrient sensing and mitochondria homeostasis. The nuclear factor erythroid 2-related factor 2 (NRF-2) serves as a pivotal regulator of the cellular stress response, and recent studies have implicated it in the pathogenesis of obesity, diabetes, and metabolic syndrome. Curcumin, a polyphenolic compound derived from turmeric, has been identified as a potent activator of NRF-2. Evidence suggests curcumin impacts obesity and metabolic disorders by modulating gut microbiota composition, increasing energy expenditure, and regulating lipid metabolism. Orlistat, an anti-obesity drug, inhibits fat absorption in the gastrointestinal tract, but its side effects limits its broader use.</p><p><strong>Objectives: </strong>The present study aims to investigate the potential synergetic effect of a hybrid combination between orlistat and curcumin. Additionally, we provide a detailed understanding of the molecular mechanisms through which this combination mitigates glucose-induced lipid accumulation in Caenorhabditis elegans, with a focus on the role of the skinhead 1 (SKN-1) transcription factor, an orthologue of NRF2.</p><p><strong>Methods: </strong>We assessed the lipid accumulation and the changes in skn-1 transcriptional activity in C. elegans using confocal GFP-based detection, alongside mRNA expression analysis of genes from lipid metabolism and oxidative stress response in wild-type, QV225 and LD1 strains. Furthermore, we evaluated locomotion, chemotaxis and mitochondrial dynamics to enhance our understanding of the proposed molecular-based model.</p><p><strong>Results: </strong>Our findings reveal that the orlistat/curcumin combination exerts an anti-obesogenic effect through SKN-1/NRF2-dependent regulation of conserved genes involved in carbohydrate and lipid metabolism in C. elegans. Moreover, the combination stimulates mitochondrial potential, further contributing to the observed synergistic effects.</p><p><strong>Conclusion: </strong>The hybrid combination of orlistat and curcumin demonstrates significant anti-obesity activity by regulating nutrient-sensing pathways through SKN-1/NRF-2 modulation. This approach may allow for the reduction of orlistat dosage, thereby minimizing its adverse effects while maintaining its therapeutic efficacy.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038848","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}
引用次数: 0
期刊
International Journal of Obesity
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