TY - JOUR
T1 - Genes that make you fat, but keep you healthy
AU - Loos, Ruth J.F.
AU - Kilpeläinen, T.O.
N1 - This article is protected by copyright. All rights reserved.
PY - 2018
Y1 - 2018
N2 - Obesity prevalence continues to rise worldwide, posing a substantial burden on people's health. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also called the metabolically healthy obese (MHO). Concurrently, up to 30% of normal weight individuals demonstrate cardiometabolic risk factors that are generally observed in obese individuals; the metabolically obese normal weight (MONW). Besides lifestyle, environmental factors and demographic factors, innate biological mechanisms are known to contribute to the etiology of the MHO and MONW phenotypes, as well. Experimental studies in animal models have shown that adipose tissue expandability, fat distribution, adipogenesis, adipose tissue vascularization, inflammation and fibrosis, and mitochondrial function are the main mechanisms that uncouple adiposity from its cardiometabolic comorbidities. We reviewed current genetic association studies to expand insights into the biology of MHO/MONW phenotypes. At least four genetic loci were identified through genome-wide association studies for body fat percentage (BF%) of which the BF%-increasing allele was associated with a protective effect on glycemic and lipid outcomes. For some, this association was mediated through favorable effects on body fat distribution. Other studies that characterized the genetic susceptibility of insulin resistance, found that a higher susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat subcutaneously or a preferential storage in the intra-abdominal cavity may be metabolically harmful. Clearly, more work remains to be done in this field, first through gene discovery, and subsequently through functional follow-up of identified genes. This article is protected by copyright. All rights reserved.
AB - Obesity prevalence continues to rise worldwide, posing a substantial burden on people's health. However, up to 45% of obese individuals do not suffer from cardiometabolic complications, also called the metabolically healthy obese (MHO). Concurrently, up to 30% of normal weight individuals demonstrate cardiometabolic risk factors that are generally observed in obese individuals; the metabolically obese normal weight (MONW). Besides lifestyle, environmental factors and demographic factors, innate biological mechanisms are known to contribute to the etiology of the MHO and MONW phenotypes, as well. Experimental studies in animal models have shown that adipose tissue expandability, fat distribution, adipogenesis, adipose tissue vascularization, inflammation and fibrosis, and mitochondrial function are the main mechanisms that uncouple adiposity from its cardiometabolic comorbidities. We reviewed current genetic association studies to expand insights into the biology of MHO/MONW phenotypes. At least four genetic loci were identified through genome-wide association studies for body fat percentage (BF%) of which the BF%-increasing allele was associated with a protective effect on glycemic and lipid outcomes. For some, this association was mediated through favorable effects on body fat distribution. Other studies that characterized the genetic susceptibility of insulin resistance, found that a higher susceptibility was associated with lower overall adiposity due to less fat accumulation at hips and legs, suggesting that an impaired capacity to store fat subcutaneously or a preferential storage in the intra-abdominal cavity may be metabolically harmful. Clearly, more work remains to be done in this field, first through gene discovery, and subsequently through functional follow-up of identified genes. This article is protected by copyright. All rights reserved.
KW - cardiovascular risk factors
KW - diabetes
KW - epidemiology
KW - genetics
KW - metabolism & endocrinology
U2 - 10.1111/joim.12827
DO - 10.1111/joim.12827
M3 - Journal article
C2 - 30144199
SN - 0955-7873
VL - 284
SP - 450
EP - 463
JO - Journal of Internal Medicine, Supplement
JF - Journal of Internal Medicine, Supplement
IS - 5
ER -
