SMIM1 absence is associated with reduced energy expenditure and excess weight
(2024) In Med (New York, N.Y.) 5(9). p.6-1095- Abstract
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... (More)
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.
(Less)
- author
- Stefanucci, Luca
; Moslemi, Camous
; Tomé, Ana R
; Virtue, Samuel
; Bidault, Guillaume
; Gleadall, Nicholas S
; Watson, Laura P E
; Kwa, Jing E
; Burden, Frances
; Farrow, Samantha
; Chen, Ji
; Võsa, Urmo
; Burling, Keith
; Walker, Lindsay
; Ord, John
; Barker, Peter
; Warner, James
; Frary, Amy
; Renhstrom, Karola
; Ashford, Sofie E
; Piper, Jo
; Biggs, Gail
; Erber, Wendy N
; Hoffman, Gary J
; Schoenmakers, Nadia
; Erikstrup, Christian
; Rieneck, Klaus
; Dziegiel, Morten H
; Ullum, Henrik
; Azzu, Vian
; Vacca, Michele
; Aparicio, Hugo Javier
; Hui, Qin
; Cho, Kelly
; Sun, Yan V
; Wilson, Peter W
; Bayraktar, Omer A
; Vidal-Puig, Antonio
; Ostrowski, Sisse R
; Astle, William J
; Olsson, Martin L
LU
; Storry, Jill R
LU
; Pedersen, Ole B
; Ouwehand, Willem H
; Chatterjee, Krishna
; Vuckovic, Dragana
and Frontini, Mattia
(Less) - author collaboration
- organization
- publishing date
- 2024-09-13
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Med (New York, N.Y.)
- volume
- 5
- issue
- 9
- pages
- 6 - 1095
- publisher
- Elsevier
- external identifiers
-
- scopus:85198207889
- pmid:38906141
- ISSN
- 2666-6340
- DOI
- 10.1016/j.medj.2024.05.015
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
- id
- 09b224f9-b708-470c-9cc7-a458920550d9
- date added to LUP
- 2024-08-28 12:25:08
- date last changed
- 2024-11-07 13:16:15
@article{09b224f9-b708-470c-9cc7-a458920550d9,
abstract = {{<p>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.</p><p>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<br>
-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.<br>
</p><p>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.</p><p>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.</p><p>FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.</p>}},
author = {{Stefanucci, Luca and Moslemi, Camous and Tomé, Ana R and Virtue, Samuel and Bidault, Guillaume and Gleadall, Nicholas S and Watson, Laura P E and Kwa, Jing E and Burden, Frances and Farrow, Samantha and Chen, Ji and Võsa, Urmo and Burling, Keith and Walker, Lindsay and Ord, John and Barker, Peter and Warner, James and Frary, Amy and Renhstrom, Karola and Ashford, Sofie E and Piper, Jo and Biggs, Gail and Erber, Wendy N and Hoffman, Gary J and Schoenmakers, Nadia and Erikstrup, Christian and Rieneck, Klaus and Dziegiel, Morten H and Ullum, Henrik and Azzu, Vian and Vacca, Michele and Aparicio, Hugo Javier and Hui, Qin and Cho, Kelly and Sun, Yan V and Wilson, Peter W and Bayraktar, Omer A and Vidal-Puig, Antonio and Ostrowski, Sisse R and Astle, William J and Olsson, Martin L and Storry, Jill R and Pedersen, Ole B and Ouwehand, Willem H and Chatterjee, Krishna and Vuckovic, Dragana and Frontini, Mattia}},
issn = {{2666-6340}},
language = {{eng}},
month = {{09}},
number = {{9}},
pages = {{6--1095}},
publisher = {{Elsevier}},
series = {{Med (New York, N.Y.)}},
title = {{SMIM1 absence is associated with reduced energy expenditure and excess weight}},
url = {{http://dx.doi.org/10.1016/j.medj.2024.05.015}},
doi = {{10.1016/j.medj.2024.05.015}},
volume = {{5}},
year = {{2024}},
}