Key result
Inhibition of miR-122 improves lipid profiles in obese rats undergoing hypoxic training via PPARβ upregulation.
Why the study?
Hypoxic exercise promotes weight loss via fatty acid metabolism regulation, potentially involving miR-122 regulation of PPARb, but the detailed mechanisms remained unknown.
Inhibition of miR-122 in skeletal muscle improves lipid profiles and promotes fatty acid metabolism via PPARβ upregulation during hypoxic exercise in obese rats.
miR-122 inhibition may enhance lipid profiles during hypoxic training in obese rats; leaves open translation to human metabolic disease.
Hypoxic exercise is an effective intervention for obesity, because it promotes weight loss by regulating fatty acid (FA) metabolism. The regulation of peroxisome proliferator-activated receptor β (PPARβ) by miR-122 may be involved in this process, but the detailed mechanisms are unknown. In order to address this issue, we probed how miR-122 affected the expression of factors associated with FA metabolism in skeletal muscle of obese rats undergoing hypoxic training. By injecting adeno-associated virus 9 containing miR-122 overexpression vector or miR-122 inhibitor into skeletal muscles of rats with a 4-week hypoxic exercise regimen, the miR-122 expression level can be regulated. Body composition and blood lipid levels were analyzed, and PPARβ, carnitine palmitoyltransferase 1b (CPT1b), acetylCoA carboxylase 2 (ACC2), and FA synthase (FAS) mRNA and protein levels were evaluated using quantitative reverse transcription quantitative PCR(RT-qPCR) and Western blot analysis. We found that miR-122 overexpression increased low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and decreased PPARβ, ACC2, and FAS expression. Conversely, miR-122 inhibition decreased TG level, increased high-density lipoprotein cholesterol (HDL-C) level, and upregulated PPARβ, ACC2, FAS, and CPT1b. These data indicated that the negative regulation of PPARβ by miR-122 promotes FA metabolism by altering the levels of the factors related to FA metabolism in skeletal muscle of obese rat under hypoxic training, thus providing molecular-level insight into the beneficial effects of this intervention.
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Wang et al. (2024) studied Obesity (n=40). miR-122 inhibition (AAV9-ZsGreen-rno-miR-122-5p inhibitor) and hypoxic exercise vs. Placebo control (AAV9-ZsGreen) with hypoxic exercise was evaluated on Serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels (p=<0.05). In obese rats undergoing hypoxic training, miR-122 inhibition significantly decreased triglyceride levels and increased HDL-C levels while upregulating PPARβ and downstream fatty acid metabolism factors.
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