Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content.

Autor:	Burchat N; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States., Sharma P; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States., Ye H; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States., Komakula SSB; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States.; Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, Poland., Dobrzyn A; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States.; Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, Warsaw, Poland., Vartanian V; Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United States., Lloyd RS; Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United States.; Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, United States., Sampath H; Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States.; Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, United States.; Center for Microbiome, Nutrition, and Health, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2021 Sep 15; Vol. 9, pp. 718962. Date of Electronic Publication: 2021 Sep 15 (Print Publication: 2021).
DOI:	10.3389/fcell.2021.718962
Abstrakt:	Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese ( A y /a ) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in A y /a mice ( A y /a Tg ) prevents increased body weight, without reducing food intake. Instead, obesity resistance in A y /a Tg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the A y /a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Burchat, Sharma, Ye, Komakula, Dobrzyn, Vartanian, Lloyd and Sampath.)
Databáze:	MEDLINE
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