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 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.