Luca Stefanucci, Camous Moslemi, Ana R Tomé, Samuel Virtue, Guillaume Bidault, Nicholas S Gleadall, Laura P E Watson, Jing E Kwa, Frances Burden, Samantha Farrow, Ji Chen, Urmo Võsa, Keith Burling, Lindsay Walker, John Ord, Peter Barker, James Warner, Amy Frary, Karola Renhstrom, Sofie E Ashford, Jo Piper, Gail Biggs, Wendy N Erber, Gary J Hoffman, Nadia Schoenmakers, Christian Erikstrup, Klaus Rieneck, Morten H Dziegiel, Henrik Ullum, Vian Azzu, Michele Vacca, Hugo Javier Aparicio, Qin Hui, Kelly Cho, Yan V Sun, Peter W Wilson, Omer A Bayraktar, Antonio Vidal-Puig, Sisse R Ostrowski, William J Astle, Martin L Olsson, Jill R Storry, Ole B Pedersen, Willem H Ouwehand, Krishna Chatterjee, Dragana Vuckovic, Mattia Frontini
{"title":"SMIM1 的缺失与能量消耗减少和体重超标有关。","authors":"Luca Stefanucci, Camous Moslemi, Ana R Tomé, Samuel Virtue, Guillaume Bidault, Nicholas S Gleadall, Laura P E Watson, Jing E Kwa, Frances Burden, Samantha Farrow, Ji Chen, Urmo Võsa, Keith Burling, Lindsay Walker, John Ord, Peter Barker, James Warner, Amy Frary, Karola Renhstrom, Sofie E Ashford, Jo Piper, Gail Biggs, Wendy N Erber, Gary J Hoffman, Nadia Schoenmakers, Christian Erikstrup, Klaus Rieneck, Morten H Dziegiel, Henrik Ullum, Vian Azzu, Michele Vacca, Hugo Javier Aparicio, Qin Hui, Kelly Cho, Yan V Sun, Peter W Wilson, Omer A Bayraktar, Antonio Vidal-Puig, Sisse R Ostrowski, William J Astle, Martin L Olsson, Jill R Storry, Ole B Pedersen, Willem H Ouwehand, Krishna Chatterjee, Dragana Vuckovic, Mattia Frontini","doi":"10.1016/j.medj.2024.05.015","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.</p><p><strong>Methods: </strong>We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1<sup>-/-</sup> individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.</p><p><strong>Findings: </strong>We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.</p><p><strong>Conclusion: </strong>This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.</p><p><strong>Funding: </strong>This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":null,"pages":null},"PeriodicalIF":12.8000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SMIM1 absence is associated with reduced energy expenditure and excess weight.\",\"authors\":\"Luca Stefanucci, Camous Moslemi, Ana R Tomé, Samuel Virtue, Guillaume Bidault, Nicholas S Gleadall, Laura P E Watson, Jing E Kwa, Frances Burden, Samantha Farrow, Ji Chen, Urmo Võsa, Keith Burling, Lindsay Walker, John Ord, Peter Barker, James Warner, Amy Frary, Karola Renhstrom, Sofie E Ashford, Jo Piper, Gail Biggs, Wendy N Erber, Gary J Hoffman, Nadia Schoenmakers, Christian Erikstrup, Klaus Rieneck, Morten H Dziegiel, Henrik Ullum, Vian Azzu, Michele Vacca, Hugo Javier Aparicio, Qin Hui, Kelly Cho, Yan V Sun, Peter W Wilson, Omer A Bayraktar, Antonio Vidal-Puig, Sisse R Ostrowski, William J Astle, Martin L Olsson, Jill R Storry, Ole B Pedersen, Willem H Ouwehand, Krishna Chatterjee, Dragana Vuckovic, Mattia Frontini\",\"doi\":\"10.1016/j.medj.2024.05.015\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.</p><p><strong>Methods: </strong>We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1<sup>-/-</sup> individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.</p><p><strong>Findings: </strong>We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.</p><p><strong>Conclusion: </strong>This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.</p><p><strong>Funding: </strong>This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.</p>\",\"PeriodicalId\":29964,\"journal\":{\"name\":\"Med\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2024-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Med\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.medj.2024.05.015\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Med","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.medj.2024.05.015","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
SMIM1 absence is associated with reduced energy expenditure and excess weight.
Background: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.
Methods: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.
Findings: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.
Conclusion: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.
Funding: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.
期刊介绍:
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.