Long-chain fatty acids regulate SIRT3 expression by affecting intracellular NAD+ levels in large yellow croaker (Larimichthys crocea)

Abstract

Sirtuin 3 (SIRT3) is a major deacetylase in the mitochondria and sensitive to diverse nutrient signals. However, how dietary fatty acids regulate SIRT3 expression remains poorly understood. Here, sirt3 gene from large yellow croaker was characterized and can be activated by the oxidized nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide mononucleotide (NMN). Moreover, the expression of SIRT3 is regulated differently by dietary fatty acids. In vivo, soybean oil increased the mRNA expression of sirt3 in head kidney. In vitro, stearic acid (SA) decreased the expression of SIRT3 in macrophages, while DHA and EPA increased the mRNA expression of sirt3. Meanwhile, all long-chain polyunsaturated fatty acids (LC-PUFAs) enhanced the protein levels of SIRT3, which was consistent with the trend of fatty acids affecting NAD+ levels. Furthermore, inhibition of NAD+de novo synthesis blocked DHA-induced increases in SIRT3 expression, and NMN supplement reversed SA-induced decreases in SIRT3 expression. In conclusion, these findings suggest that dietary fatty acids may regulate SIRT3 expression by affecting intracellular NAD+ synthesis. Regarding the important role of SIRT3 in regulating mitochondrial function, appropriate activation of SIRT3 may be an important way to alleviate metabolic disorders in aquaculture.