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HIF‐1α regulates a single bout of exercise‐induced hepatic expression of glucose and lipid metabolism related genes
Author(s) -
Luo Beibei,
Xiang Dao,
Chen Peijie,
Hu Yiping
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1014.1
Subject(s) - in vivo , medicine , endocrinology , luciferase , bioluminescence imaging , homeostasis , energy homeostasis , glucose homeostasis , metabolism , chemistry , biology , gene , insulin , receptor , insulin resistance , biochemistry , transfection , microbiology and biotechnology
Exercise increases the energy demand, disrupting the hepatic glucose and lipid metabolic homeostasis. A single bout of exercise could induce tissue blood flow redistribution by which the blood flow is decreased in the splanchnic circulation. The hypoxia‐inducible factor (HIF) 1α is pivotal in the transcriptional response to oxygen flux. Therefore, we hypothesize that HIF‐1α plays an important role in the regulation of hepatic metabolism related genes expression after a single bout of exercise. The noninvasive in vivo bioluminescence imaging was applied to monitor HIF‐1α expression after exercise in ROSA26 ODD‐Luc/ + mouse model (ODD‐Luc) that ubiquitously expresses a bioluminescent reporter consisting of firefly luciferase fused to a region of HIF‐1α. We found that one session of 30min swimming exercise markedly increase in vivo HIF‐1α in the gastrointestinal (GI) system and liver. Then two small molecule inhibitors were respectively intraperitoneal (i.p.) injected to the ODD‐Luc mice: DMOG (100mg/kg), which blocks prolyl hydroxylase domain (PHD) protein thus stabilizes HIF‐1α; and PX‐478 (100mg/kg), which inhibits HIF‐1α. The data was shown that the DMOG administration increased in vivo HIF‐1α in the GI system and liver; PX‐478 administration reduced the in vivo HIF‐1α expression after one session of 30min swimming. 8‐week male FVB/N mice were divided into 5 groups (n=6 per group): one session of 30min swimming (SWIM), swimming with PX‐478 i.p. injection (SWIM‐PX478), PX‐478 i.p. injection (PX478), DMOG i.p. injection (DMOG) and control (CON). Gene expression profiling experiments were performed on mouse liver cDNA samples from each group using RT 2 Profiler PCR Arrays including over 240 genes related to glucose metabolism, fatty acid metabolism, and lipoprotein signaling and cholesterol metabolism. It was found that one session of exercise‐induced genes expression were significantly different ( P <0.001) between the SWIM‐PX478 and SWIM mice, including G6pc, Pck1, Pdk1, Scd1, Acadm, Acox1, Ctp1, Cpt2, Crot, Hmgcs2, Srebf and Ldlr. The pattern of one session of exercise induced hepatic metabolism related genes expression was similar between the DMOG and SWIM groups. Albumin Cre mediated, hepatocyte specific deletions of HIF‐1α or PHD2 mouse models were also developed to verify the function of HIF‐1α in regulating the hepatic glucose and lipid metabolism related genes expression after one session of 30min swimming. In conclusion, these results demonstrate an important role for the HIF‐1α in the regulation of hepatic metabolism related genes expression after a single bout of exercise. Support or Funding Information The National Natural Science Foundation of China (31471135) and the China Postdoctoral Science Foundation funded project.