Journal
BIOESSAYS
Volume 39, Issue 5, Pages -Publisher
WILEY
DOI: 10.1002/bies.201600227
Keywords
adipose tissue; insulin resistance; NAD(+); NAMPT; obesity; PPAR gamma; SIRT1
Categories
Funding
- National Institute of Diabetes and Kidney Diseases [DK104995, DK 56341, DK 37948, DK 20579]
- KL2 Career Developmental Awards [UL1 TR00450]
- Longer Life Foundation
- Sumitomo Life Welfare and Culture Foundation
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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.
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