Dr. Bray Links

Sunday, July 2, 2017

Mechanisms, Pathophysiology, and Management of Obesity — NEJM

The review article by Heymsfield and Wadden (Jan. 19 issue)1 is valuable with respect to the clinical management of obesity, but information about the contribution of mitochondrial genes to obesity is not included. Mitochondrial dysfunction is associated with an accumulation of fat that can occur during aging and in patients with obesity, the metabolic syndrome, or diabetes mellitus.2

Zheng et al.3 found that obese participants with a high metabolic syndrome score have increased DNA methylation in the mitochondrial genes MT-CO1 and MT-ND6 and in the mitochondrion-related nuclear gene PPARGC1A. Flaquer et al.4 conducted a study using samples obtained from 6528 participants in the KORA (Cooperative Health Research in the Region of Augsburg) studies and found that two mitochondrial single-nucleotide polymorphisms (SNPs) located in the cytochrome c oxidase subunit genes (MT-CO1 and MT-CO3) and three mitochondrial SNPs located in the NADH dehydrogenase subunit genes (MT-ND1, MT-ND2, and MT-ND4L) were significantly associated with a higher body-mass index (BMI). Latorre-Pellicer et al.5 systematically characterized conplastic mice (mice in which the nuclear genome of one mouse is backcrossed into the cytoplasm of another, so that the nuclear genes and mitochondrial genes are from different parents) throughout their lifespan. They found that the mitochondrial DNA haplotype profoundly influences mitochondrial proteostasis and generation of reactive oxygen species, insulin signaling, telomere shortening, the development of obesity, and mitochondrial dysfunction. These findings highlight the importance of the contribution of mitochondrial genetic variants to the risk of a high BMI.


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