Related Experiment Video
Updated: Jan 25, 2026
Adult and Embryonic Skeletal Muscle Microexplant Culture and Isolation of Skeletal Muscle Stem Cells
Published on: September 21, 2010
Inhibitory effect of 17β‑estradiol on triglyceride synthesis in skeletal muscle cells is dependent on ESR1 and not
Quan Liu1, Rui Li1, Guanjun Chen2
1Department of Clinical Pharmacy, Class 2014, School of Pharmacy, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
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.
Insights
17β‑estradiol (E2) reduces triglyceride synthesis and improves insulin resistance in skeletal muscle by interacting with estrogen receptor 1 (ESR1). This pathway inhibits pathways promoting fat accumulation and enhances metabolic health.
Area of Science:
- Endocrinology
- Metabolic Research
- Molecular Biology
Background:
- Estrogen plays a crucial role in metabolic regulation.
- Estrogen deficiency, such as post-ovariectomy, is linked to increased triglyceride synthesis and insulin resistance in skeletal muscle.
- Understanding the molecular mechanisms of estrogen's action in muscle is vital for metabolic health.
Purpose of the Study:
- To investigate the inhibitory effects of 17β‑estradiol (E2) on triglyceride synthesis and insulin resistance in skeletal muscle.
- To elucidate the underlying molecular mechanisms involving estrogen receptors (ESR1/2) and key metabolic pathways.
- To assess the role of E2 in an in vivo rat model and in vitro C2C12 myotube cells.
Main Methods:
- Ovariectomy (OVX) in female rats, followed by E2 treatment.
- Biochemical marker analysis, histological examination of tissues (uterus, liver, skeletal muscle).
- In vitro studies using C2C12 myotubes treated with palmitic acid (PA), E2, ESR1 agonist (PPT), and ESR2 agonist (DPN).
- Analysis of gene and protein expression (ESR1/2, PPARα, CD36, FASN, PLIN2, p-ACACA, p-AKT, p-MAPK8) via RT-qPCR and Western blotting.
Main Results:
- E2 treatment inhibited OVX-induced body weight gain, muscle triglyceride accumulation, and insulin resistance.
- OVX altered the expression of key proteins and genes; E2 treatment restored these levels.
- In C2C12 cells, E2 and the ESR1 agonist (PPT) reversed PA-induced changes, while the ESR2 agonist (DPN) had no significant effect.
- E2 primarily acts through ESR1 to modulate the CD36-PPARα pathway.
Conclusions:
- 17β‑estradiol (E2) effectively mitigates triglyceride accumulation and insulin resistance in skeletal muscle.
- E2 exerts its beneficial effects by interacting with estrogen receptor 1 (ESR1).
- The CD36-PPARα pathway is a key mediator of E2's action in improving skeletal muscle lipid metabolism and insulin sensitivity.
Related Concept Videos
01:48Classification of Skeletal Muscle Fibers
Slow-Twitch Muscle Fibers
Slow oxidative, muscle fibers appear red due to large numbers of capillaries and high levels of...
01:29Relaxation of Skeletal Muscles
When an action potential reaches the axon terminal, it depolarizes the membrane and opens voltage-gated sodium channels. Sodium ions enter the cell, further depolarizing the presynaptic membrane. This depolarization causes voltage-gated calcium channels to open....
01:15Overview of Skeletal Muscle
00:55Skeletal Muscle Anatomy
01:28Disorders of the Skeletal Muscle
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
01:19Naming Skeletal Muscles
The key factors used in naming muscles include: