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Publication
Importance of Adipose Tissue NAD+ Biology in Regulating Metabolic Flexibility.
Authors Franczyk MP, Qi N, Stromsdorfer KL, Li C, Yamaguchi S, Itoh H, Yoshino M, Sasaki
Y, Brookheart RT, Finck BN, DeBosch BJ, Klein S, Yoshino J
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Endocrinology
Year 2021
Date Published 3/1/2021
Volume : Pages 162 : Not Specified
PubMed Reference 33543238
Abstract Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme that regulates
cellular energy metabolism in many cell types. The major purpose of the present
study was to test the hypothesis that NAD+ in white adipose tissue (WAT) is a
regulator of whole-body metabolic flexibility in response to changes in insulin
sensitivity and with respect to substrate availability and use during feeding
and fasting conditions. To this end, we first evaluated the relationship between
WAT NAD+ concentration and metabolic flexibility in mice and humans. We found
that WAT NAD+ concentration was increased in mice after calorie restriction and
exercise, 2 enhancers of metabolic flexibility. Bariatric surgery-induced 20%
weight loss increased plasma adiponectin concentration, skeletal muscle insulin
sensitivity, and WAT NAD+ concentration in people with obesity. We next analyzed
adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout
(ANKO) mice, which have markedly decreased NAD+ concentrations in WAT. ANKO mice
oxidized more glucose during the light period and after fasting than control
mice. In contrast, the normal postprandial stimulation of glucose oxidation and
suppression of fat oxidation were impaired in ANKO mice. Data obtained from
RNA-sequencing of WAT suggest that loss of NAMPT increases inflammation, and
impairs insulin sensitivity, glucose oxidation, lipolysis, branched-chain amino
acid catabolism, and mitochondrial function in WAT, which are features of
metabolic inflexibility. These results demonstrate a novel function of WAT
NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility,
and provide new insights into the role of adipose tissue NAD+ biology in
metabolic health.




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