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

Shintaro Yamaguchi, Jun Yoshino

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

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.

Original languageEnglish
Article number1600227
JournalBioEssays
Volume39
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • NAD
  • NAMPT
  • PPARγ
  • SIRT1
  • adipose tissue
  • insulin resistance
  • obesity

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