Inhibitory effect of 17β‑estradiol on triglyceride synthesis in skeletal muscle cells is dependent on ESR1 and not ESR2

Liu,Quan; Li,Rui; Chen,Guanjun; Wang,Jianming; Hu,Bingfeng; Li,Chaofei; Zhu,Xiaohuan; Lu,Yunxia

doi:10.3892/mmr.2019.10189

Inhibitory effect of 17β‑estradiol on triglyceride synthesis in skeletal muscle cells is dependent on ESR1 and not ESR2

Authors:
- Quan Liu
- Rui Li
- Guanjun Chen
- Jianming Wang
- Bingfeng Hu
- Chaofei Li
- Xiaohuan Zhu
- Yunxia Lu
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Affiliations: Department of Clinical Pharmacy, Class 2014, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Center of Scientific Research, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Dalian Maple International School, Dalian, Liaoning 116100, P.R. China, The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: April 24, 2019 https://doi.org/10.3892/mmr.2019.10189
Pages: 5087-5096
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the inhibitory effects and the mechanisms underlying 17β‑estradiol (E2) effects on triglyceride synthesis and insulin resistance in skeletal muscle tissues and cells. Ovariectomy (OVX) was performed on 6‑month‑old female rats treated with or without E2. Subsequently, various serum biochemical markers were measured. Additionally, pathological alterations of the uterus, liver and skeletal muscle were analyzed, and the content of triglycerides (TG) in muscle was detected. Differentiated myotubes formed by C2C12 cells were treated with palmitic acid (PA) or pretreated with E2, estrogen receptor (ESR) 1 agonist propylpyrazoletriol (PPT) and ESR2 agonist diarylpropionitrile (DPN). Subsequently, the mRNA or protein expression levels of ESR1/2, peroxisome proliferator activated receptor α (PPARα), CD36 molecule (CD36), fatty acid synthase (FASN), perilipin 2 (PLIN2), phosphorylated acetyl‑CoA carboxylase α (p‑ACACA), p‑AKT serine/threonine kinase (p‑AKT) and p‑mitogen‑activated protein kinase 8 (p‑MAPK8) were analyzed in skeletal muscle or in C2C12 cells by reverse transcription‑semi‑quantitative polymerase chain reaction and western blotting. The present results suggested that treatment with E2 inhibited OVX‑induced body weight gain, TG accumulation and insulin resistance. The protein or mRNA expression levels of ESR1, CD36, PPARα, p‑ACACA and p‑AKT were decreased, whereas the protein or mRNA expression levels of ESR2, PLIN2, FASN and p‑MAPK8 were increased in the OVX group. Of note, treatment with E2 restored the expression levels of the aforementioned factors. In C2C12 cells, treatment with E2 or PPT reversed the alterations induced by treatment with PA. In contrast, pretreatment with DPN did not influence the effect of PA. Collectively, E2 was able to interact with ESR1, thus activating the CD36‑PPARα pathway, decreasing the level of TG in the muscles and improving insulin resistance in skeletal muscles and C2C12 cells.

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