Adipose tissue NAD + biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice.
Level 5 - mechanism / opinion, no new human data
Bench and animal knockout experiment with observational human tissue biopsy analysis
PubMed 31694884 · doi:10.1073/pnas.1909917116
What was done
The authors generated mouse models with tissue-specific knockouts of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in NAD+ biosynthesis: ANKO mice (lacking NAMPT in both brown and white adipose tissue) and BANKO mice (lacking NAMPT specifically in brown adipose tissue). They evaluated thermogenic gene expression, mitochondrial function, oxygen consumption, and temperature responses under acute cold exposure, fasting, and beta-adrenergic stimulation (norepinephrine, CL-316243). They tested metabolic rescue using nicotinamide mononucleotide (NMN) and measured NAMPT expression in supraclavicular adipose biopsies from human subjects exposed to cold.
What was found
The abstract reports qualitative directional findings without numerical values: - ANKO mice displayed impaired BAT mitochondrial and thermogenic gene programs and blunted rectal temperature, BAT temperature, and oxygen consumption responses to cold, fasting, and beta-adrenergic agonists. - Loss of NAMPT in white adipose tissue reduced adrenergic-mediated lipolytic activity, associated with inactivation of the NAD+-SIRT1-caveolin-1 axis. - NMN administration rescued the metabolic abnormalities induced by NAMPT deficiency in mice. - BANKO mice had similar cellular alterations in BAT to ANKO mice but maintained normal whole-body thermogenic and lipolytic responses. - Human supraclavicular adipose tissue showed increased NAMPT expression during cold exposure.
Why it matters
This study establishes that white adipose tissue NAD+ biosynthesis is necessary to fuel adaptive thermogenesis through lipolysis. It outlines a clear mechanistic pathway for how NAD+ availability and precursor supplementation support mammalian energy homeostasis during environmental and metabolic stress.
Limits
The study is conducted primarily in genetically modified rodent models. The abstract provides no sample sizes for the mouse cohorts or human subjects, nor does it provide quantitative effect sizes, confidence intervals, or p-values. Human data are limited to observational changes in tissue gene expression.
Cited by
- context Heat and cold stress upregulate the enzyme nicotinamide phosphoribosyltransferase (NAMPT), which converts nicotinamide to NAD+.