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Link to original content: http://pubmed.ncbi.nlm.nih.gov/32278117/
Depot-specific regulation of NAD+/SIRTs metabolism identified in adipose tissue of mice in response to high-fat diet feeding or calorie restriction - PubMed Skip to main page content
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. 2020 Jun:80:108377.
doi: 10.1016/j.jnutbio.2020.108377. Epub 2020 Mar 19.

Depot-specific regulation of NAD+/SIRTs metabolism identified in adipose tissue of mice in response to high-fat diet feeding or calorie restriction

Xiaojing Wei  1 , Ru Jia  2 , Guan Wang  3 , Shangyu Hong  4 , Lin Song  1 , Bo Sun  1 , Ke Chen  1 , Nan Wang  1 , Qiqi Wang  1 , Xiao Luo  5 , Jianqun Yan  6
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Depot-specific regulation of NAD+/SIRTs metabolism identified in adipose tissue of mice in response to high-fat diet feeding or calorie restriction

Xiaojing Wei et al. J Nutr Biochem. 2020 Jun.

Abstract

Deteriorated nicotinamide adenine dinucleotide (NAD+)/sirtuins (SIRTs) metabolism in adipose tissue is implicated in diet-induced obesity, while calorie restriction (CR)-induced beneficial effects require sufficient NAD+ biosynthesis. Mechanistic links have not been defined. This study aims to identify changes of specific components of NAD+/SIRTs system in white adipose tissue (WAT) and brown adipose tissue (BAT) of mice upon energy imbalance, focusing on key enzymes in NAD+ salvage (Nampt, Nmnat1, Nrk1), clearance (Nnmt, Aox1, Cyp2e1) and consumption pathways (Sirt1, Sirt2, Sirt3, Sirt6, Parp1). Male C57BL/6J mice were fed ad libitum with the standard laboratory chow diet, high-fat diet (HFD) or 40% CR diet, respectively. The epididymal and inguinal WAT (eWAT and iWAT) and interscapular BAT (iBAT) were harvested for histological, NAD+ assay, gene and protein expression analysis after 16 weeks of dietary regimen. HFD decreased, while CR increased, the NAD+ and NADH levels in eWAT, iWAT and iBAT. NAD+ content negatively correlated with plasma cholesterol, TNF-α levels and calorie intake, while it positively correlated with plasma adiponectin level. The change trend of SIRT1 is quite the same as that of NAD+/NADH ratio. Nmnat1 gene is sensitive to energy imbalance in WAT but not in BAT. Nrk1 gene expression was decreased in eWAT and iWAT but increased in iBAT of HFD mice. Nnmt mRNA and protein abundance was increased in iWAT of HFD mice. Nampt, Cyp2e1 and Sirt3 were the most robust genes responding to energy imbalance. In summary, adipose tissue responds to long-term energy excess or shortage with depot-specific transcriptional activation or repression of NAD+/SIRTs metabolic components.

Keywords: Adipose tissue; Calorie restriction; High-fat diet; NAD(+) metabolism; Sirtuins.

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