Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling

This work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism. Materials &

Nonalcoholic fatty liver disease (NAFLD) is a primary contributor to liver-related morbidity and mortality. Asprosin has been reported to be implicated in NAFLD. Aims: This work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism. Materials &

Collectively, Asprosin inhibition suppressed lipid accumulation and inflammation to obstruct NAFLD through AMPK/p38 signaling.

The weight of NAFLD mice induced by a high-fat diet was detected. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) examined serum Asprosin expression. RT-qPCR and western blot analysis examined Asprosin expression in mice liver tissues. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were implemented. Biochemical kits tested liver enzyme levels in mice serum and liver tissues. Hematoxylin and eosin staining evaluated liver histology. Liver weight was also tested and oil red O staining estimated lipid accumulation. RT-qPCR and western blot analysis analyzed the expression of gluconeogenesis-, fatty acid biosynthesis-, fatty acid oxidation-, and inflammation-associated factors. Besides, western blot analysis examined the expression of AMP-activated protein kinase (AMPK)/p38 signaling-associated factors. In palmitic acid (PA)-treated mice hepatocytes, RT-qPCR and western blot analysis examined Asprosin expression. Lipid accumulation, gluconeogenesis, fatty acid biosynthesis, fatty acid oxidation, and inflammation were appraised again.

Asprosin was overexpressed in the serum and liver tissues of NAFLD mice and PA-treated mice hepatocytes. Asprosin interference reduced mice body and liver weight, improved glucose tolerance and diminished liver injury in vivo. Asprosin knockdown alleviated lipid accumulation and inflammatory infiltration both in vitro and in vivo. Additionally, Asprosin absence activated AMPK/p38 signaling and AMPK inhibitor Compound C reversed the impacts of Asprosin on lipid accumulation and inflammatory response.