Abstract: Mitochondria play an important role in regulating lipid metabolism as an important place for energy metabolism. This study investigated the effect of 1-deoxynojirimycin (DNJ) on mitochondrial synthesis and mitophagy in the hepatocytes of obese mice. An obese mouse model was established by feeding Kunming a high-fat diet, and then the obese mice were administered with DNJ at doses of 8.0, 4.0 and 2.0 mg/(kg mb·d) for 45 days. At the end of this period, serum and liver parameters were determined. The results showed that compared with the obese control group, high-dose DNJ could delay body mass gain, mitigate inflammation, significantly increase?serum adiponectin?by 43.19% and 29.58% (P < 0.01) in female and male mice. In addition, it could increase?fibroblast growth factor 21 (FGF21) in female mice by 37.03% (P < 0.01), and improve FGF21 resistance in male mice. Also it could upregulate the mRNA expression of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) α1 as well as the mRNA expression of peroxisome proliferator activated receptor γ coactivator-1α, nuclear respiratory factor 1 and unc-51 like kinase 1, all related to mitochondrial biosynthesis, to increase the corresponding protein levels by 28.27% and 43.99% (P < 0.01), 50.25% and 40.26% (P < 0.01), and 19.24% and 22.76% (P < 0.05) in female and male mice, and increase carnitine palmitoyltransferase1 activity by 58.05% and 49.60% (P < 0.05) in female and male mice, respectively. Conclusion: DNJ can control body mass by reducing inflammation, improving FGF21 and adiponectin levels, upregulating the mRNA expression of AMPKα1 to promote mitochondrial biosynthesis and autophagy and simultaneously activating the fatty acid oxidation rate-limiting enzyme, carnitine palmitoyltransferase 1 to promote fatty acid breakdown.

Key words: 1-deoxynojirimycin; mitochondrial biosynthesis; mitophagy; obesity