Importance of Adipose Tissue NAD+ Biology in Regulating Metabolic Flexibility
Open accessAbstract
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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Reduced NAD+ accompanies a loss of metabolic flexibility.
“reduced NAD + accompanies a loss of metabolic flexibility [166].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [166]
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- Authors
- Franczyk, M. P., Qi, N., Stromsdorfer, K. L., Li, C., Yamaguchi, S., Itoh, H., Yoshino, M., Sasaki, Y., Brookheart, R. T., Finck, B. N., DeBosch, B. J., Klein, S., & Yoshino, J.
- Affiliations
- Washington University in St. Louis (US)
- University of Michigan (US)
- Keio University (JP)
- Corresponding author
- Yoshino, Jun
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2021-01-12
- Volume
- 162
- Issue
- 3
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC7853299
- OpenAlex
- W3120844915
- Cited by
- 23
- References
- 57
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 4
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (DK104995, DK115764, DK117657, DK056341, DK020579, DK052574, CA91842, UL1TR002345, DK089503, DK020572)
- Longer Life Foundation (1U2CDK110678-01)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- NAD+, white adipose tissue, metabolic flexibility, visfatin, caloric restriction, physical activity, bariatric surgery, obesity, insulin sensitivity, glucose oxidation, fat oxidation, adiponectin, adipose tissue inflammation, lipolysis, branched-chain amino acids, mitochondrial function, fasting, substrate availability
- MeSH terms
- Adipose Tissue, Adult, Animals, Energy Metabolism, Fatty Acids, Female, Humans, Lipolysis, Male, Mice, Inbred C57BL, Middle Aged, NAD, Cytokines, Mice, Knockout, Postprandial Period, Mice, Nicotinamide Phosphoribosyltransferase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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