Obesity poses a global health challenge and is a major risk factor for diabetes mellitus, cardiovascular diseases, hypertension, stroke and certain kinds of cancers. Although the effects of nicotinamide (NAM) on liver metabolism and diseases were well documented, its effects on adipose tissue are yet to be characterized. Herein, we found that NAM supplementation significantly reduced fat mass and improved glucose tolerance in obese mice. Proteomic analysis revealed that NAM supplementation upregulates mitochondrial proteins while quantitative polymerase chain reaction showed that PPARα and PGC1α were both upregulated in adipose tissues, proposing that NAM increased mitochondrial biogenesis in adipose tissue. Indeed, NAM treatment increased proteins related to mitochondrial functions including oxidative phosphorylation, fatty acid oxidation, and TCA cycle. Furthermore, isotope-tracing assisted metabolic profiling revealed that NAM activated NAMPT and increased cellular NAD+ level by 30%. Unexpectedly, we found that NAM also increased glucose derived amino acids to enhance glutathione synthesis for maintaining cellular redox homeostasis. Taken together, our results demonstrated that NAM reprogramed cellular metabolism, enhanced adipose mitochondrial functions to ameliorate symptoms associated with obesity.
Keywords: Glutathione; Mitochondrial biogenesis; Nicotinamide; Nicotinamide adenine dinucleotide (NAD+); Obesity.
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