Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy

Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decad...

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Bibliographic Details
Published in:BioEssays 2017-05, Vol.39 (5), p.n/a
Main Authors: Yamaguchi, Shintaro, Yoshino, Jun
Format: Article
Language:English
Subjects:
adipose tissue
Adipose Tissue - metabolism
Animals
Biosynthesis
Humans
Insulin resistance
Insulin Resistance - physiology
Metabolism
Models, Biological
NAD
NAD - metabolism
NAMPT
Nicotinamide Phosphoribosyltransferase - metabolism
Obesity
Obesity - drug therapy
Obesity - etiology
Obesity - metabolism
PPAR gamma - metabolism
PPARγ
Protein Processing, Post-Translational
SIRT1
Sirtuin 1 - metabolism
Translational Medical Research
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Summary:Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT‐mediated NAD+ biosynthesis, together with its key downstream mediator, namely the NAD+‐dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue‐dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT‐mediated NAD+ biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD+ biology. Obesity‐associated insulin resistance is an important risk factor for type 2 diabetes and cardiovascular disease. Emerging evidence suggests that impairment of adipose tissue NAMPT‐NAD+‐SIRT1 axis leads to the development of insulin resistance in multiple metabolic organs. These findings have provided important mechanistic and clinical insights into obesity and insulin resistance.
ISSN:0265-9247
1521-1878
DOI:10.1002/bies.201600227