AdipoRon may counter -associated fatty liver by improving metabolic state and hepatic circadian gene regulation in rats.
Evidence
In an in vivo PCOS rat model with hepatosteatosis, AdipoRon reduced lipid accumulation, insulin resistance, lipogenesis, hyperandrogenism, adiponectin deficiency, and altered clock-gene histone marks.
Caveat
The findings are preliminary animal and epigenetic evidence, so clinical benefit in women with PCOS-associated was not tested.
Simplified
Persistent lower levels of adiponectin are associated with hyperandrogenism, predisposing women to . This study elucidated the therapeutic potential of a small molecule adiponectin receptor agonist-AdipoRon, utilizing an in-vivo PCOS rat model mimicking the manifestation of PCOS along with hepatosteatosis. Our study demonstrated that Adiporon reduced lipid accumulation in PCOS-associated NAFLD by alleviating insulin resistance & lipogenesis. AdipoRon also reversed hyperandrogenism and adiponectin deficiency in PCOS animals. In addition, AdipoRon was found to restore altered PCOS-induced hepatic circadian gene expression (Bmal1, Clock, Per3, Cry2, Reverba, and Rora). Interestingly, at the epigenetic level, global transcription activation marks, i.e., H3K4me3, H3K9/14ac, and H3K36me2, were upregulated in disease conditions. Furthermore, our ChIP data confirmed that circadian genes Bmal1, Reverba, And Rora are epigenetically regulated. ChIP assay data showed an increased H3K36 dimethylation at the Bmal1 and Rora promoter, whereas a significant decrease was observed at the Reverbα promoter in PCOS-associated NAFLD. AdipoRon ameliorated these PCOS-induced epigenetic alterations, modulating the hepatic circadian gene expression. We present the preliminary evidence illustrating the epigenetic modulation of AdipoRon, thereby regulating hepatic circadian gene expression. This study provides insights regarding the therapeutic potential of AdipoRon in PCOS-associated NAFLD, which can be of profound clinical significance.
Key numbers
< 0.001
Reduction in plasma glucose
Plasma glucose levels significantly decreased after AdipoRon treatment.
< 0.001
Improvement in HOMA-IR index
HOMA-IR index was significantly improved with AdipoRon treatment.
< 0.001
Increase in serum adiponectin levels
Serum adiponectin levels increased significantly in AdipoRon-treated animals.
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