Song 2020 Life Sci

Song K, Zhang Y, Ga Q, Bai Z, Ge RL (2020) High-altitude chronic hypoxia ameliorates obesity-induced non-alcoholic fatty liver disease in mice by regulating mitochondrial and AMPK signaling. Life Sci 252:117633.

» PMID: 32289432

Song Kang, Zhang Yifan, Ga Qin, Bai Zhenzhong, Ge Ri-Li (2020) Life Sci

Abstract: High-fat intake induces obesity and non-alcoholic fatty liver disease (NAFLD). However, high-altitude chronic hypoxia might alleviate NAFLD progression through improved mitochondrial function and AMP-activated protein kinase (AMPK) signaling. We hypothesized that high-altitude chronic hypoxia would have protective effects against NAFLD development.

C57BL/6J mice were randomly divided into control (normal diet and altitude 50 m), CHH (normal diet and altitude 4300 m), HFD (high-fat diet and altitude 50 m), and HFD-CHH (high-fat diet and altitude 4300 m) groups. After being maintained for 8 weeks under the appropriate conditions, mice were evaluated.

The degree of liver lipid accumulation and expression of the lipid synthesis-related genes acetyl-CoA carboxylase1 (ACC1), fatty acid synthesis (FAS), and sterol regulatory element binding protein-1c (SREBP-1c) were reduced in the HFD-CHH group; however, expression of the lipolysis-related gene carnitine palmitoyl transferase 1 (CPT1) was increased. Furthermore, in addition to increased expression of mitochondrial biogenesis-related genes, mitochondrial respiratory function and mitochondrial DNA content were elevated in the HFD-CHH group compared to those in the HFD group. The HFD-CHH group also exhibited significantly increased antioxidation activity and decreased reactive oxygen species production (P < 0.05). Finally, AMPK signaling in the liver was activated and the expression of phosphorylated-AMPK (P-AMPK) was significantly increased in the HFD-CHH group.

Collectively, our findings suggest that high altitude-induced hypoxia might improve impaired mitochondrial function and activate AMPK signaling in obesity-induced NAFLD. High-altitude chronic hypoxia could be a new treatment strategy for obesity-induced NAFLD.

Labels: MiParea: Respiration Pathology: Obesity Stress:Hypoxia Organism: Mouse Tissue;cell: Liver Preparation: Homogenate

Coupling state: LEAK, OXPHOS, ET Pathway: F, N, NS HRR: Oxygraph-2k

2020-04