TY - JOUR
T1 - Adipose tissue NAD+ biology in obesity and insulin resistance
T2 - From mechanism to therapy
AU - Yamaguchi, Shintaro
AU - Yoshino, Jun
N1 - Funding Information:
The authors apologize to those whose work is not cited due to space limitations. We would like to thank members in the Yoshino lab for excellent discussion and suggestion in this manuscript. JY is supported by grants from the National Institute of Diabetes and Kidney Diseases DK104995, DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Research Center), KL2 Career Developmental Awards (UL1 TR00450), and the Longer Life Foundation. S.Y. is supported by the Sumitomo Life Welfare and Culture Foundation. The authors have declared no conflict of interest.
Publisher Copyright:
© 2017 WILEY Periodicals, Inc.
PY - 2017/5
Y1 - 2017/5
N2 - 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.
AB - 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.
KW - NAD
KW - NAMPT
KW - PPARγ
KW - SIRT1
KW - adipose tissue
KW - insulin resistance
KW - obesity
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U2 - 10.1002/bies.201600227
DO - 10.1002/bies.201600227
M3 - Review article
C2 - 28295415
AN - SCOPUS:85015159301
SN - 0265-9247
VL - 39
JO - BioEssays
JF - BioEssays
IS - 5
M1 - 1600227
ER -
