{"title":"Bone Health and Obesity Treatments: It's Time to Give Bone Its Due","authors":"Robert L. Dubin","doi":"10.1002/oby.70074","DOIUrl":"10.1002/oby.70074","url":null,"abstract":"","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"15-16"},"PeriodicalIF":4.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396086","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}
Yujiao Zu, Mark Mikhael, Jose Andrade, Shane Scoggin, Mohammad Yosofvand, Hanna Moussa, William T. Festuccia, Naima Moustaid-Moussa
Objective
Mitochondrial glycerol-3-phosphate dehydrogenase (GPD2) is a crucial enzyme in the glycerophosphate shuttle, linking glycolysis, lipogenesis, and oxidative phosphorylation, making it a potential target for obesity treatment. Given the metabolic benefits of eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, we hypothesized that EPA modulates the GPD2-centered glycerophosphate shuttle to reduce adiposity, glucose intolerance, and inflammation while increasing energy expenditure.
Methods
Male and female GPD2 knockout (KO) and wild-type (WT) littermates were fed a high-fat diet (HF) without or with an 18 g EPA/kg (EPA) diet for 13 weeks. Body weight, glucose tolerance, and metabolic profiles were assessed, and blood and tissues were collected following euthanasia.
Results
Male GPD2 KO mice exhibited reduced adiposity and lower lipid accumulation in hepatic and adipose tissues compared to WT males. These effects were linked to lipid metabolism and beige fat activation. EPA supplementation reduced body weight and promoted glucose clearance in both WT and KO males, with enhanced hepatic lipid oxidation. However, GPD2 deficiency and EPA had minimal metabolic effects in females.
Conclusions
Our findings highlight potential mechanisms by which GPD2 combats obesity by mediating lipid metabolism. Our findings further demonstrate the sex-dependent nature of EPA's metabolic benefits, independent of GPD2 deficiency.
目的：线粒体甘油-3-磷酸脱氢酶（GPD2）是甘油磷酸穿梭过程中的关键酶，连接糖酵解、脂肪生成和氧化磷酸化，使其成为肥胖治疗的潜在靶点。考虑到二十碳五烯酸（EPA）（一种omega-3多不饱和脂肪酸）的代谢益处，我们假设EPA可以调节以gpd2为中心的甘油磷酸穿梭，从而减少肥胖、葡萄糖耐受不良和炎症，同时增加能量消耗。方法：将GPD2敲除（KO）和野生型（WT）的公母幼崽分别饲喂高脂肪饲粮（HF），不添加或添加18 g EPA/kg （EPA）的饲粮，持续13周。评估体重、葡萄糖耐量和代谢谱，并在安乐死后收集血液和组织。结果：与WT雄性相比，雄性GPD2 KO小鼠表现出脂肪减少，肝脏和脂肪组织中的脂质积累更低。这些影响与脂质代谢和米色脂肪活化有关。EPA的补充降低了WT和KO雄性的体重，促进了葡萄糖清除，并增强了肝脏脂质氧化。然而，GPD2缺乏和EPA对女性的代谢影响很小。结论：我们的研究结果强调了GPD2通过调节脂质代谢来对抗肥胖的潜在机制。我们的研究结果进一步证明了EPA代谢益处的性别依赖性，与GPD2缺乏无关。
{"title":"Effects of Eicosapentaenoic Acid on the Glycerophosphate Shuttle-Regulated Inflammatory and Thermogenic Responses","authors":"Yujiao Zu, Mark Mikhael, Jose Andrade, Shane Scoggin, Mohammad Yosofvand, Hanna Moussa, William T. Festuccia, Naima Moustaid-Moussa","doi":"10.1002/oby.70053","DOIUrl":"10.1002/oby.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Mitochondrial glycerol-3-phosphate dehydrogenase (GPD2) is a crucial enzyme in the glycerophosphate shuttle, linking glycolysis, lipogenesis, and oxidative phosphorylation, making it a potential target for obesity treatment. Given the metabolic benefits of eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, we hypothesized that EPA modulates the GPD2-centered glycerophosphate shuttle to reduce adiposity, glucose intolerance, and inflammation while increasing energy expenditure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male and female GPD2 knockout (KO) and wild-type (WT) littermates were fed a high-fat diet (HF) without or with an 18 g EPA/kg (EPA) diet for 13 weeks. Body weight, glucose tolerance, and metabolic profiles were assessed, and blood and tissues were collected following euthanasia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Male GPD2 KO mice exhibited reduced adiposity and lower lipid accumulation in hepatic and adipose tissues compared to WT males. These effects were linked to lipid metabolism and beige fat activation. EPA supplementation reduced body weight and promoted glucose clearance in both WT and KO males, with enhanced hepatic lipid oxidation. However, GPD2 deficiency and EPA had minimal metabolic effects in females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight potential mechanisms by which GPD2 combats obesity by mediating lipid metabolism. Our findings further demonstrate the sex-dependent nature of EPA's metabolic benefits, independent of GPD2 deficiency.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"150-161"},"PeriodicalIF":4.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396060","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}
Yufan Li, Reema Sharma, Abigail Usiyevich, Xiwen Shen, Kelly W. Zhang, Koulik Khamaru, Bridget A. Matikainen-Ankney
Objective
Despite successful weight loss, many individuals with obesity regain weight, yet cognitive factors in the weight loss state remain unclear. Here, we tested whether obesity induces deficits in cognitive flexibility, a core component of reinforcement learning (RL), after body weight normalizes.
Methods
Male and female C57BL/6J mice were exposed to high-fat diet-induced obesity followed by weight loss. Weight loss and control mice were tested on a modified probabilistic reversal learning (PRL) task to assess cognitive flexibility and a progressive-ratio (PR) task to evaluate motivation. RL modeling was applied to dissociate latent decision-making parameters.
Results
Post-weight-loss mice exhibited persistent impairments in PRL efficiency. Males showed reduced late-phase reversal efficiency (p < 0.001), while females showed early-phase inefficiency but later recovery (p < 0.05). RL modeling revealed reduced learning rates in both sexes, indicating impaired value updating despite intact motivation, as PR performance did not differ between groups. Across tasks, food intake remained unchanged, suggesting reduced efficiency reflected cognitive inflexibility rather than diminished appetite.
Conclusions
Weight loss after obesity produced sex-specific RL deficits. These findings dissociated motivational drive from cognitive flexibility and highlighted maladaptive decision-making as a feature of the weight loss state. This demonstrates the need for targeted interventions addressing post-weight-loss cognitive barriers.
{"title":"Weight Loss After Obesity Disrupts Cognitive Flexibility Through Reinforcement Learning Strategies","authors":"Yufan Li, Reema Sharma, Abigail Usiyevich, Xiwen Shen, Kelly W. Zhang, Koulik Khamaru, Bridget A. Matikainen-Ankney","doi":"10.1002/oby.70057","DOIUrl":"10.1002/oby.70057","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Despite successful weight loss, many individuals with obesity regain weight, yet cognitive factors in the weight loss state remain unclear. Here, we tested whether obesity induces deficits in cognitive flexibility, a core component of reinforcement learning (RL), after body weight normalizes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male and female C57BL/6J mice were exposed to high-fat diet-induced obesity followed by weight loss. Weight loss and control mice were tested on a modified probabilistic reversal learning (PRL) task to assess cognitive flexibility and a progressive-ratio (PR) task to evaluate motivation. RL modeling was applied to dissociate latent decision-making parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Post-weight-loss mice exhibited persistent impairments in PRL efficiency. Males showed reduced late-phase reversal efficiency (<i>p</i> < 0.001), while females showed early-phase inefficiency but later recovery (<i>p</i> < 0.05). RL modeling revealed reduced learning rates in both sexes, indicating impaired value updating despite intact motivation, as PR performance did not differ between groups. Across tasks, food intake remained unchanged, suggesting reduced efficiency reflected cognitive inflexibility rather than diminished appetite.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Weight loss after obesity produced sex-specific RL deficits. These findings dissociated motivational drive from cognitive flexibility and highlighted maladaptive decision-making as a feature of the weight loss state. This demonstrates the need for targeted interventions addressing post-weight-loss cognitive barriers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"188-198"},"PeriodicalIF":4.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396069","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}
Zachary J. Fennel, Anu S. Kurian, Paul-Emile Bourrant, Chad M. Skiles, Robert J. Castro, Elena M. Yee, Scott A. Greilach, Hans S. Keirstead, Gabriel Nistor, Nicole C. Berchtold, Thomas E. Lane, Micah J. Drummond
Objective
In this study, we investigated the effects of a stem cell-derived secretome product on adiposity and tissue quality and insulin and glucose levels in obese mice and those undergoing dietary weight loss.
Methods
Following 16 weeks of high fat diet mice received acute (4 weeks) biweekly intramuscular injections with vehicle or secretome while remaining on a high fat diet (HFD vs. HFD-S) or during weight loss upon return to a normal chow diet (HFD/WL vs. HFD/WL-S).
Results
After 4 weeks of treatment, HFD-S mice had greater lean mass (vs HFD), muscle weights, and quadriceps myofibrillar size and improved muscle quality (capillary density and fibrosis). HFD/WL-S mice had accelerated whole-body fat loss and improved glucose handling, fasting insulin levels, and HOMA-IR. In both secretome-treated groups (HFD-S and HFD/WL-S), liver steatosis and fibrosis were improved and similar to chow controls.
Conclusions
Together, these results support that a stem cell secretome treatment may be useful to improve tissue quality and metabolic health during obesity and weight loss.
目的：在本研究中，我们研究了干细胞来源的分泌组产品对肥胖小鼠和饮食减肥小鼠的肥胖和组织质量以及胰岛素和葡萄糖水平的影响。方法：高脂饮食16周后，小鼠在保持高脂饮食（HFD vs. HFD- s）或体重减轻后恢复正常饮食（HFD/WL vs. HFD/WL- s）期间接受急性（4周）双周肌肉注射载药或分泌组。结果：治疗4周后，HFD- s小鼠有更大的瘦质量（与HFD相比）、肌肉重量和股四头肌肌纤维大小，肌肉质量（毛细血管密度和纤维化）得到改善。HFD/WL-S小鼠加速了全身脂肪的减少，改善了葡萄糖处理、空腹胰岛素水平和HOMA-IR。在两个分泌组（HFD- s和HFD/WL-S）中，肝脏脂肪变性和纤维化得到改善，与对照组相似。结论：总之，这些结果支持干细胞分泌组治疗可能有助于改善肥胖和减肥期间的组织质量和代谢健康。
{"title":"Stem Cell Secretome Treatment Reduces Adiposity and Improves Glucose Handling During Obesity and Weight Loss in Mice","authors":"Zachary J. Fennel, Anu S. Kurian, Paul-Emile Bourrant, Chad M. Skiles, Robert J. Castro, Elena M. Yee, Scott A. Greilach, Hans S. Keirstead, Gabriel Nistor, Nicole C. Berchtold, Thomas E. Lane, Micah J. Drummond","doi":"10.1002/oby.70068","DOIUrl":"10.1002/oby.70068","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this study, we investigated the effects of a stem cell-derived secretome product on adiposity and tissue quality and insulin and glucose levels in obese mice and those undergoing dietary weight loss.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following 16 weeks of high fat diet mice received acute (4 weeks) biweekly intramuscular injections with vehicle or secretome while remaining on a high fat diet (HFD vs. HFD-S) or during weight loss upon return to a normal chow diet (HFD/WL vs. HFD/WL-S).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After 4 weeks of treatment, HFD-S mice had greater lean mass (vs HFD), muscle weights, and quadriceps myofibrillar size and improved muscle quality (capillary density and fibrosis). HFD/WL-S mice had accelerated whole-body fat loss and improved glucose handling, fasting insulin levels, and HOMA-IR. In both secretome-treated groups (HFD-S and HFD/WL-S), liver steatosis and fibrosis were improved and similar to chow controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Together, these results support that a stem cell secretome treatment may be useful to improve tissue quality and metabolic health during obesity and weight loss.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 2","pages":"382-393"},"PeriodicalIF":4.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12850608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373570","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}
Faith Anne N. Heeren, Kathleen R. Ruddiman, Courtney Simmons, Brian N. White, Byron C. Jaeger, Nicholas M. Pajewski, Stephanie A. Hooker, Deborah B. Horn, Katy Martin-Fernandez, Kimberly A. Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis
Objective
This study aimed to apply The Lancet Diabetes & Endocrinology criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.
Methods
The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with “no obesity,” “pre-clinical obesity,” and “clinical obesity.”
Results
Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m2 [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m2 [SD 3.5]), and 80.5% had clinical obesity (mean BMI 35.9 kg/m2 [SD 4.3]). Participants with no/pre-clinical obesity had lower mean SF-12 mental component scores and greater baseline engagement with weight control strategies compared to those with clinical obesity. Participants with clinical obesity were older and, by definition, had a greater burden of cardiometabolic risk factors.
Conclusions
Among clinical trial participants eligible for obesity pharmacotherapy, 19.5% were classified as having no/pre-clinical obesity using the Lancet criteria. Applying the criteria was complicated in a well-resourced trial setting, which suggests potential challenges in implementing these guidelines in real-world practice.
{"title":"Application of the Lancet Commission Criteria for the Diagnosis of Obesity to a Clinical Trials Population: The LEAP Trial","authors":"Faith Anne N. Heeren, Kathleen R. Ruddiman, Courtney Simmons, Brian N. White, Byron C. Jaeger, Nicholas M. Pajewski, Stephanie A. Hooker, Deborah B. Horn, Katy Martin-Fernandez, Kimberly A. Gudzune, Caroline Blackwell Young, Jamy Ard, Kristina Henderson Lewis","doi":"10.1002/oby.70070","DOIUrl":"10.1002/oby.70070","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to apply <i>The Lancet Diabetes & Endocrinology</i> criteria for diagnosing obesity among clinical trial participants and understand participants' characteristics by obesity status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The criteria were operationalized and applied to baseline data from the Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial (NCT05176626). Excess adiposity, organ and tissue dysfunction, and limitations to daily activities were assessed. We examined differences between participants with “no obesity,” “pre-clinical obesity,” and “clinical obesity.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 860 participants, 0.8% had no obesity (mean BMI 29.0 kg/m<sup>2</sup> [SD 0.6]), 18.7% had pre-clinical obesity (mean BMI 35.2 kg/m<sup>2</sup> [SD 3.5]), and 80.5% had clinical obesity (mean BMI 35.9 kg/m<sup>2</sup> [SD 4.3]). Participants with no/pre-clinical obesity had lower mean SF-12 mental component scores and greater baseline engagement with weight control strategies compared to those with clinical obesity. Participants with clinical obesity were older and, by definition, had a greater burden of cardiometabolic risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among clinical trial participants eligible for obesity pharmacotherapy, 19.5% were classified as having no/pre-clinical obesity using the Lancet criteria. Applying the criteria was complicated in a well-resourced trial setting, which suggests potential challenges in implementing these guidelines in real-world practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"58-64"},"PeriodicalIF":4.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380540","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}
Iftikhar Khan, Amna Pervaiz Kayani, Ehsanullah Alokozay
{"title":"Critical Appraisal of Healthcare Resource Use and Costs in Digital Weight Loss Intervention Participants vs. Nonparticipants","authors":"Iftikhar Khan, Amna Pervaiz Kayani, Ehsanullah Alokozay","doi":"10.1002/oby.70085","DOIUrl":"10.1002/oby.70085","url":null,"abstract":"","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"7-8"},"PeriodicalIF":4.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373531","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}
Jane Shearer, Morris H. Scantlebury, Oghenefejiro Erome-Utunedi, Anamika Choudhary, Jennifer A. Thompson, Christina Ohland, Kathy D. McCoy, Chunlong Mu
Objective
Acid-sensing ion channels are proton-activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiology remains unclear. This study investigates how systemic deletion of Asic1a influences obesity, metabolic, and gut-based outcomes.
Methods
Employing male and female rats with systemic Asic1a deletion (Asic1a−/−), metabolic, gut, and fecal microbiota (16S rRNA sequencing) measures were assessed following chow diet or high-fat diet administration for 8 weeks. Fecal microbiota transplantation into germ-free mice was carried out as a proof-of-concept approach to assess the gut microbiota's direct impact.
Results
On a chow diet, Asic1a deletion resulted in significant gains in body weight, fat mass, glucose intolerance, and insulin resistance in both male and female rats compared to wild-type controls. These effects were exacerbated with high-fat diet administration. Asic1a−/− reshaped the gut microbiota, characterized by the enrichment of Bacteroides and Akkermansia. Microbiota transplantation from Asic1a−/− rats to recipient germ-free mice increased body weight gain relative to those from wild-type rats, implicating the potential role of gut microbiota.
Conclusions
Results provide evidence that ASIC1a plays a role in regulating metabolic homeostasis and the gut microbiota impacting body composition.
{"title":"Role of Acid-Sensing Ion Channels 1a in the Regulation of Obesity and the Gut Microbiota","authors":"Jane Shearer, Morris H. Scantlebury, Oghenefejiro Erome-Utunedi, Anamika Choudhary, Jennifer A. Thompson, Christina Ohland, Kathy D. McCoy, Chunlong Mu","doi":"10.1002/oby.70059","DOIUrl":"10.1002/oby.70059","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Acid-sensing ion channels are proton-activated ion channels predominantly found in the nervous system. They are well known to affect metabolic and neurological health, yet their role in obesity and gut physiology remains unclear. This study investigates how systemic deletion of <i>Asic1a</i> influences obesity, metabolic, and gut-based outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Employing male and female rats with systemic <i>Asic1a</i> deletion (<i>Asic1a</i>\u0000 <sup>−/−</sup>), metabolic, gut, and fecal microbiota (16S rRNA sequencing) measures were assessed following chow diet or high-fat diet administration for 8 weeks. Fecal microbiota transplantation into germ-free mice was carried out as a proof-of-concept approach to assess the gut microbiota's direct impact.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>On a chow diet, <i>Asic1a</i> deletion resulted in significant gains in body weight, fat mass, glucose intolerance, and insulin resistance in both male and female rats compared to wild-type controls. These effects were exacerbated with high-fat diet administration. <i>Asic1a</i>\u0000 <sup>−/−</sup> reshaped the gut microbiota, characterized by the enrichment of <i>Bacteroides</i> and <i>Akkermansia</i>. Microbiota transplantation from <i>Asic1a</i>\u0000 <sup>−/−</sup> rats to recipient germ-free mice increased body weight gain relative to those from wild-type rats, implicating the potential role of gut microbiota.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Results provide evidence that ASIC1a plays a role in regulating metabolic homeostasis and the gut microbiota impacting body composition.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 2","pages":"372-381"},"PeriodicalIF":4.7,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12850573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373553","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}
Individuals with obesity often struggle to resist the temptation of palatable food, which may be linked to impaired inhibitory control—a crucial cognitive function for regulating eating behavior. Enhancing inhibitory control over food-related memories has been proposed as a potential intervention strategy for obesity. The right dorsolateral prefrontal cortex (dlPFC) plays a key role in regulating reward-driven impulses. However, it remains unclear whether neuromodulating the right dlPFC can selectively strengthen inhibitory control over food-related memories, particularly in individuals with overweight/obesity status who exhibit heightened reward sensitivity and diminished executive function.
Methods
This study employed a food Think/No-Think (TNT) training combined with HD-tDCS targeting the right dlPFC to assess its effects on inhibitory control over food-related memory in individuals with overweight/obesity.
Results
Both groups with healthy weight and overweight/obesity demonstrated significant improvements in memory suppression following anodal stimulation. Notably, individuals with overweight/obesity exhibited greater reductions in memory intrusion at the early stage, suggesting they may benefit more from anodal stimulation in resisting memory intrusions.
Conclusions
These findings highlight the potential of combining neuromodulation with cognitive training as a promising intervention for obesity, providing both theoretical insights and empirical evidence for future prevention and treatment approaches.
{"title":"Neural Stimulation of Prefrontal Cortex Improves Food-Related Memory Suppression","authors":"Jingjing Li, Yuan Gao, Jiangming Chen, Yuchen Zhang, Yaru Yang, Xiao Gao","doi":"10.1002/oby.70052","DOIUrl":"10.1002/oby.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Individuals with obesity often struggle to resist the temptation of palatable food, which may be linked to impaired inhibitory control—a crucial cognitive function for regulating eating behavior. Enhancing inhibitory control over food-related memories has been proposed as a potential intervention strategy for obesity. The right dorsolateral prefrontal cortex (dlPFC) plays a key role in regulating reward-driven impulses. However, it remains unclear whether neuromodulating the right dlPFC can selectively strengthen inhibitory control over food-related memories, particularly in individuals with overweight/obesity status who exhibit heightened reward sensitivity and diminished executive function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study employed a food Think/No-Think (TNT) training combined with HD-tDCS targeting the right dlPFC to assess its effects on inhibitory control over food-related memory in individuals with overweight/obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both groups with healthy weight and overweight/obesity demonstrated significant improvements in memory suppression following anodal stimulation. Notably, individuals with overweight/obesity exhibited greater reductions in memory intrusion at the early stage, suggesting they may benefit more from anodal stimulation in resisting memory intrusions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings highlight the potential of combining neuromodulation with cognitive training as a promising intervention for obesity, providing both theoretical insights and empirical evidence for future prevention and treatment approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"199-208"},"PeriodicalIF":4.7,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373507","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}
Maria Descamps-Solà, Florijan Jalševac, Adrià Vilalta, Margalida Fontcuberta, Harry Park, Carmen Aguilar, Teresa Auguet, Raúl Beltrán-Debón, Esther Rodríguez-Gallego, Montserrat Pinent, Ximena Terra, Anna Ardévol
Objective
Obesity is a chronic disease with various causes and diverse treatments, including dietary restriction and bariatric surgery. Bitter taste receptors (TAS2Rs), found in the oral cavity and gastrointestinal tract (GIT), are implicated in digestive and metabolic regulation, but their role in obesity remains unclear. This study investigates intestinal TAS2R expression concerning obesity and bariatric surgery outcomes.
Methods
TASas2r expression was assessed in intestinal segments of female rats fed a cafeteria diet for 17 weeks. Additionally, jejunal TAS2R expression was measured in women with class III obesity, with or without metabolic syndrome (MS), undergoing Roux-en-Y gastric bypass (RYGB). Associations with weight loss at 12 months postsurgery were evaluated.
Results
In rats, cafeteria diet significantly reduced Tas2r expression, especially in the jejunum and duodenum. In women with MS, higher expression of TAS2R13 and TAS2R20 correlated with greater weight loss post-after RYGB. In those without metabolic syndrome, higher TAS2R5 expression showed similar associations. TAS2R expression was strongly linked to surgical outcomes. In rats, Tas2r108 (ileum) and Tas2r144 (jejunum) expression levels differed between obese and lean animals.
Conclusions
Intestinal TAS2Rs may influence metabolic regulation and bariatric surgery outcomes, suggesting their potential as therapeutic targets in female obesity. Further studies should clarify their underlying mechanisms.
{"title":"Exploring the Role of TAS2Rs in Obesity: Insights From Human and Rat Models","authors":"Maria Descamps-Solà, Florijan Jalševac, Adrià Vilalta, Margalida Fontcuberta, Harry Park, Carmen Aguilar, Teresa Auguet, Raúl Beltrán-Debón, Esther Rodríguez-Gallego, Montserrat Pinent, Ximena Terra, Anna Ardévol","doi":"10.1002/oby.70055","DOIUrl":"10.1002/oby.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Obesity is a chronic disease with various causes and diverse treatments, including dietary restriction and bariatric surgery. Bitter taste receptors (TAS2Rs), found in the oral cavity and gastrointestinal tract (GIT), are implicated in digestive and metabolic regulation, but their role in obesity remains unclear. This study investigates intestinal TAS2R expression concerning obesity and bariatric surgery outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>TASas2r expression was assessed in intestinal segments of female rats fed a cafeteria diet for 17 weeks. Additionally, jejunal TAS2R expression was measured in women with class III obesity, with or without metabolic syndrome (MS), undergoing Roux-en-Y gastric bypass (RYGB). Associations with weight loss at 12 months postsurgery were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In rats, cafeteria diet significantly reduced Tas2r expression, especially in the jejunum and duodenum. In women with MS, higher expression of TAS2R13 and TAS2R20 correlated with greater weight loss post-after RYGB. In those without metabolic syndrome, higher TAS2R5 expression showed similar associations. TAS2R expression was strongly linked to surgical outcomes. In rats, Tas2r108 (ileum) and Tas2r144 (jejunum) expression levels differed between obese and lean animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Intestinal TAS2Rs may influence metabolic regulation and bariatric surgery outcomes, suggesting their potential as therapeutic targets in female obesity. Further studies should clarify their underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"34 1","pages":"162-174"},"PeriodicalIF":4.7,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12724055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373564","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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