title: Adipose tissue NAD+biology in obesity and insulin resistance: From mechanism to therapy.
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.
authors.affiliation: Center for Human Nutrition, Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Center for Human Nutrition, Division of Geriatrics and Nutritional Science, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshino
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D056564:Sirtuin 1 / Q000378:metabolism; D057170:Translational Research, Biomedical
chemical_list: D047495:PPAR gamma; D009243:NAD; D054409:Nicotinamide Phosphoribosyltransferase; D056564:Sirtuin 1
keywords: NAD+; NAMPT; PPARγ; SIRT1; adipose tissue; insulin resistance; obesity