Ugonin J improves metabolic disorder and ameliorates nonalcoholic fatty liver disease by regulating the AMPK/AKT signaling pathway.

Abstract

Closely associated with visceral obesity, hepatic steatosis resulting from non-alcoholic fatty liver disease (NAFLD) exacerbates insulin resistance. Developing effective drugs to treat NAFLD is imperative. Here, we investigated the pharmacological mechanism of ugonin J (UJ) in controlling metabolic disorder and ameliorating NAFLD pathophysiology in diet-induced obese mice. The effects of UJ were assessed in 5-week-old C57BL/6 J mice fed a high-fat diet (HFD) for 12 weeks. UJ treatment averted HFD-induced body weight gain by reducing fat deposition in adipose tissues and reduced HFD-induced hyperlipidemia and hepatic inflammation. UJ also improved HFD-induced glucose tolerance and insulin resistance. Moreover, the mode of action of UJ was analyzed in palmitate (PA)-induced steatotic human HuS-E/2 hepatocytes and in hyperglycemia-simulating rat BRIN-BD11 pancreatic β cells. In PA-induced steatotic human hepatocytes, UJ treatment promoted lipid clearance via pAMPK, pACC and CPT-1 upregulation and SREBP-1c downregulation. Interestingly, UJ upregulated Akt activity in hepatocytes and increased insulin secretion from β cells in acute insulin secretion tests. Taken together, UJ improved adipocyte hypertrophy, hyperinsulinemia, hyperglycemia, hyperlipidemia and fat deposition in livers. UJ also reduced fatty acid accumulation by modulating key metabolic regulators. Our findings demonstrated the therapeutic potential of UJ for the treatment of NAFLD and diet-induced metabolic disorders.

• Authors: Ting-Chen Chang, Wei-Chung Chiou, Wei-Han Lai, Hsiu-Chen Huang, Yu-Ling Huang, Hui-Kang Liu, Yu-Chih Liang, Cheng Huang
• Journal: Pharmacological research (Pharmacol Res) Vol. 163 Pg. 105298 (01 2021) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 33220422 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Adipokines
• Fatty Acids
• Insulin
• Glucose

Topics

• Adipokines (blood)
• Adipose Tissue (drug effects, pathology)
• Animals
• Cell Line
• Cells, Cultured
• Diet, High-Fat
• Fatty Acids (metabolism)
• Glucose (metabolism)
• Hepatocytes (drug effects, metabolism)
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Insulin-Secreting Cells (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Male
• Metabolic Diseases (drug therapy, metabolism)
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (drug therapy, metabolism)
• Obesity (drug therapy, metabolism)
• Rats
• Weight Gain (drug effects)
• Mice