SMIM1 absence is associated with reduced energy expenditure and excess weight
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
SMIM1 absence is associated with reduced energy expenditure and excess weight. / DBDS Genetic Consortium.
I: Med, 17.06.2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - SMIM1 absence is associated with reduced energy expenditure and excess weight
AU - Stefanucci, Luca
AU - Moslemi, Camous
AU - Tomé, Ana R
AU - Virtue, Samuel
AU - Bidault, Guillaume
AU - Gleadall, Nicholas S
AU - Watson, Laura P E
AU - Kwa, Jing E
AU - Burden, Frances
AU - Farrow, Samantha
AU - Chen, Ji
AU - Võsa, Urmo
AU - Burling, Keith
AU - Walker, Lindsay
AU - Ord, John
AU - Barker, Peter
AU - Warner, James
AU - Frary, Amy
AU - Renhstrom, Karola
AU - Ashford, Sofie E
AU - Piper, Jo
AU - Biggs, Gail
AU - Erber, Wendy N
AU - Hoffman, Gary J
AU - Schoenmakers, Nadia
AU - Erikstrup, Christian
AU - Rieneck, Klaus
AU - Dziegiel, Morten H
AU - Ullum, Henrik
AU - Azzu, Vian
AU - Vacca, Michele
AU - Aparicio, Hugo Javier
AU - Hui, Qin
AU - Cho, Kelly
AU - Sun, Yan V
AU - Wilson, Peter W
AU - Bayraktar, Omer A
AU - Vidal-Puig, Antonio
AU - Ostrowski, Sisse R
AU - Astle, William J
AU - Olsson, Martin L
AU - Storry, Jill R
AU - Pedersen, Ole B
AU - Ouwehand, Willem H
AU - Chatterjee, Krishna
AU - Vuckovic, Dragana
AU - Frontini, Mattia
AU - DBDS Genetic Consortium
N1 - Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2024/6/17
Y1 - 2024/6/17
N2 - 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.
AB - 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.
U2 - 10.1016/j.medj.2024.05.015
DO - 10.1016/j.medj.2024.05.015
M3 - Journal article
C2 - 38906141
JO - Med
JF - Med
SN - 2666-6359
ER -
ID: 398644501