AdipoRon prevents myostatin-induced upregulation of fatty acid synthesis and downregulation of insulin activity in a mouse hepatocyte line

Physiol Rep, 2019 · DOI: 10.14814/phy2.14152 · Published: July 1, 2019

Simple Explanation

The study investigates how myostatin (Mstn) and AdipoRon affect liver cells, focusing on fat metabolism and insulin action. Mstn, typically known for its role in muscle, can cause fat accumulation in the liver and reduce the cells' ability to respond to insulin. AdipoRon, a drug that mimics adiponectin, was tested for its ability to counteract Mstn's effects. The research found that AdipoRon can protect liver cells from the harmful effects of Mstn, helping to maintain normal fat metabolism and insulin sensitivity. The study also looked at the molecular pathways involved. Mstn affects the Smad2/3 pathway, while AdipoRon influences the AMPK/PPARa pathways. The results suggest that AdipoRon can block Mstn's activation of the Smad2/3 pathway, offering a potential way to treat fat metabolism and insulin action disorders.

Study Duration

3 days

Participants

FL83B, a mouse hepatocyte cell line

Evidence Level

Not specified

Key Findings

1
Myostatin (Mstn) increases fatty acid accumulation and desensitizes cellular responses to insulin in hepatocytes.
2
AdipoRon protects against Mstn-induced defects in hepatic gene expression and function, reversing the effects of Mstn on AMPK and PPARa activities.
3
AdipoRon prevents Mstn-induced activation of the Smad2/3 pathway, suggesting crosstalk between Mstn-induced Smad2/3 and adiponectin-induced AMPK/PPARa pathways.

Research Summary

This study investigated the interactive effects of myostatin (Mstn) and AdipoRon on hepatic gene expression and function in a mouse hepatocyte line. Mstn increased fatty acid accumulation and desensitized cellular responses to insulin. AdipoRon, a synthetic adiponectin receptor agonist, protected against Mstn-induced defects in hepatic gene expression and function. These effects of Mstn were associated with reduced AMPK and PPARa activities, which were reversed by AdipoRon. AdipoRon was able to prevent Mstn-induced activation of the Smad2/3 pathway, suggesting potential therapeutic roles for AdipoRon in disorders of fat metabolism and insulin action.

Practical Implications

Therapeutic Potential

AdipoRon, as an adiponectin receptor agonist, may serve a therapeutic role to reduce the hepatic contribution to the disorders of fat metabolism and insulin action.

Crosstalk Identification

The data suggest crosstalk between Mstn-induced Smad2/3 and adiponectin-induced AMPK/PPARa pathways, which may play important roles in the regulation of hepatic gene expression.

Target for Liver Diseases

Mstn may be a candidate responsible for the downregulation of adiponectin receptors in liver of patients with non-alcoholic steatosis.

Study Limitations

1
The study was conducted in a mouse hepatocyte cell line (FL83B), which may not fully represent the complexity of in vivo liver physiology.
2
The specific molecular mechanisms by which AdipoRon inhibits Mstn action in hepatocytes remain uncertain and require further investigation.
3
The study did not explore the effects of AdipoRon on downstream targets of Smad, such as FOXO1, which could provide further insights into the mechanisms of action.

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