Hypoxic exercise may represent a novel therapeutic strategy to reduce and prevent
obesity through the regulation of lipid metabolism. During hypoxic exercise, the targeting of
peroxisome proliferator-activated receptor gamma (PPARγ) by miR-27b has been proposed to be one of the mechanisms involved in the modulation of lipid metabolism. We have previously shown that miR-27b can repress PPARγ and lipid metabolism-associated factors, thereby affecting lipid metabolism during hypoxic exercise in a rat model of
obesity. In the current study, we aimed to confirm the role of miR-27b in the regulation of lipid metabolism. First, miR-27b expression was either upregulated or downregulated through the injection of adeno-associated virus (AAV) 9 containing a miR-27b expression cassette or miR-27b-3p inhibitor, respectively, into the right gastrocnemius muscle of obese rats. The rats were then subjected to a 4-week program of hypoxic exercise, and a series of parameters related to lipid metabolism were systematically evaluated, including body composition, blood
lipid levels, miR-27b
RNA levels, and
mRNA and
protein levels of PPARγ and those of its downstream lipid metabolism-associated factors. No significant differences were found in body composition between rats expressing different levels of miR-27b. However, regarding blood
lipids, miR-27b overexpression led to increased concentrations of
triglycerides (TG),
low-density lipoprotein cholesterol (
LDL-C), and
free fatty acids (FFAs), while inhibition of miR-27b decreased the total
cholesterol (TC) level and increased that of
high-density lipoprotein cholesterol (HDL-C). At the
mRNA level, miR-27b overexpression downregulated the expression of Pparγ, but upregulated that of lipid metabolism-associated factors such as heart-type
fatty acid-binding protein (
H-FABP),
fatty acid transport protein 1 (FATP1), adipose
triglyceride lipase (ATGL), and
lipoprotein lipase (LPL), whereas miR-27b inhibition elicited the opposite effect; however, inhibition of miR-27b led to
elevated cholesterol 7 alpha-hydroxylase (CYP7A1) and
fatty acid translocase 36 (CD36) levels. Similarly, at the
protein level, miR-27b overexpression promoted a decrease in the concentration of PPARγ, whereas miR-27b inhibition led to an increase in PPARγ levels, as well as those of CYP7A1, CD36, ATGL, and LPL. Overall, our results indicated that hypoxic exercise regulates lipid metabolism via the miR-27b/PPARγ pathway and modulates ATGL and LPL expression through inducing their post-transcriptional modifications.