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Phoenixin 14 Inhibits High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Experimental Mice
Fan Yang1, Ping Huang1, Liandong Shi2
1Department of Endocrinology, Guilin People's Hospital, Guilin, Guangxi 541002, People's Republic of China.
Introduction:
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The development of NAFLD is closely associated with hepatic lipotoxicity, inflammation, and oxidative stress. The new concept of NAFLD treatment is to seek molecular control of lipid metabolism and hepatic redox hemostasis. Phoenixin is a newly identified neuropeptide with pleiotropic effects. This study investigated the effects of phoenixin 14 against high-fat diet (HFD)-induced NAFLD in mice.
Materials And Methods:
For this study, we used HFD-induced NAFLD mice models to analyze the effect of phonenixin14. The mice were fed on HFD and normal diet and also given phoenixin 14 (100 ng/g body weight) by gastrogavage for 10 weeks. The peripheral blood samples were collected for biochemical assays. The liver tissues were examined for HFD-induced tissue fibrosis, lipid deposition and oxidative activity including SOD, GSH, and MDA. The liver tissues were analyzed for the inflammatory cytokines and oxidative stress pathway genes.
Results:
The results indicate that phoenixin 14 significantly ameliorated HFD-induced obesity and fatty liver. The biochemical analysis of blood samples revealed that phoenixin 14 ameliorated HFD-induced elevated circulating alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, and triglyceride levels, suggesting that phoenixin 14 has a protective role in liver function and lipid metabolism. Hematoxylin-eosin (HE) and Oil Red O staining of the liver showed that phoenixin 14 alleviated HFD-induced tissue damage and lipid deposition in the liver. Furthermore, the mice administered with phoenixin 14 had increased hepatic SOD activity, increased production of GSH and reduced MDA activity, as well as reduced production of TNF-α and IL-6 suggesting that phoenixin 14 exerts beneficial effects against inflammation and ROS. The findings suggest an explanation of how mechanistically phoenixin 14 ameliorated HFD-induced reduced activation of the SIRT1/AMPK and NRF2/HO-1 pathways.
Conclusion:
Collectively, this study revealed that phoenixin 14 exerts a protective effect in experimental NAFLD mice. Phoenixin could be of the interest in preventive modulation of NAFLD.
Insights
Phoenixin 14 effectively combats nonalcoholic fatty liver disease (NAFLD) in mice by reducing obesity, liver damage, and inflammation. This neuropeptide shows promise for preventing and treating NAFLD by improving lipid metabolism and oxidative stress.
Area of Science:
- Hepatology
- Metabolic Disease Research
- Neuropeptide Signaling
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition linked to lipotoxicity, inflammation, and oxidative stress.
- Current NAFLD treatment strategies focus on managing lipid metabolism and hepatic redox balance.
- Phoenixin, a novel neuropeptide, exhibits diverse biological effects warranting investigation in metabolic disorders.
Purpose of the Study:
- To investigate the therapeutic potential of phoenixin 14 in a mouse model of high-fat diet (HFD)-induced NAFLD.
- To elucidate the molecular mechanisms underlying phoenixin 14's effects on lipid metabolism, inflammation, and oxidative stress in NAFLD.
Main Methods:
- Establishment of HFD-induced NAFLD mouse models.
- Administration of phoenixin 14 via oral gavage for 10 weeks.
- Assessment of liver function, lipid deposition, oxidative stress markers (SOD, GSH, MDA), inflammatory cytokines (TNF-α, IL-6), and key signaling pathways (SIRT1/AMPK, NRF2/HO-1).
Main Results:
- Phoenixin 14 significantly reduced HFD-induced obesity and hepatic steatosis.
- Treatment with phoenixin 14 improved liver function by lowering ALT, AST, total cholesterol, and triglyceride levels.
- Phoenixin 14 alleviated liver tissue damage, decreased lipid accumulation, and reduced oxidative stress and inflammation markers, while activating SIRT1/AMPK and NRF2/HO-1 pathways.
Conclusions:
- Phoenixin 14 demonstrates significant protective effects against experimental NAFLD in mice.
- These findings suggest phoenixin 14 as a potential therapeutic agent for modulating NAFLD progression.
