Endocrinology Journal Article

Mineralocorticoid Receptors in Insulin Resistance

November 15, 2022
 

Jack L Hulse, Javad Habibi, Aderonke E Igbekele, Bingyue Zhang, Jessie Li, Adam Whaley-Connell, James R Sowers, Guanghong Jia
Endocrinology, Volume 163, Issue 11, November 2022, bqac145
https://doi.org/10.1210/endocr/bqac145

Abstract

Excess circulating lipids increase total intramyocellular (IMC) lipid content and ectopic fat storage, resulting in lipotoxicity and insulin resistance in skeletal muscle. Consumption of a diet high in fat and refined sugars—a Western diet (WD)—has been shown to activate mineralocorticoid receptors (MRs) and promote insulin resistance. However, our understanding of the precise mechanisms by which enhanced MR activation promotes skeletal muscle insulin resistance remains unclear. In this study, we investigated the mechanisms by which enhanced MR signaling in soleus muscle promotes ectopic skeletal muscle lipid accumulation and related insulin resistance. Six-week-old C57BL/6J mice were fed either a mouse chow diet or a WD with or without spironolactone (1 mg/kg/day) for 16 weeks. Spironolactone attenuated 16 weeks of WD-induced in vivo glucose intolerance and insulin resistance, and improved soleus insulin metabolic signaling. Improved insulin sensitivity was accompanied by increased glucose transporter 4 (Glut4) expression in conjunction with decreased soleus free fatty acid and IMC lipid content, as well as CD36 expression. Additionally, spironolactone prevented WD-induced soleus mitochondria dysfunction. Furthermore, MR signaling also mediated WD/aldosterone-induced reductions in soleus microRNA (miR)-99a, which was identified to negatively target CD36 and prevented palmitic acid-induced increases in CD36 expression, lipid droplet formation, mitochondria dysfunction, and insulin resistance in C2C12 cells. These data indicate that inhibition of MR activation with spironolactone prevented diet-induced abnormal expression of miR-99a, which had the capacity to reduce CD36, leading to reduced IMC lipid content and improved soleus mitochondria function and insulin sensitivity.

Read the article

 

You may also like...

Publishing Benefits

Author Resource Center

We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.
Publishing Benefits

Author Resource Center

We provide our journal authors with a variety of resources for increasing the discoverability and citation of their published work. Use these tools and tips to broaden the impact of your article.

Thematic Issue

Latest Thematic Issue

immuno-endocrinology
Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.

Read our special collections of Endocrine Society journal articles, curated by topic, Altmetric Attention Scores, and Featured Article designations.

Back to top

Who We Are

For 100 years, the Endocrine Society has been at the forefront of hormone science and public health. Read about our history and how we continue to serve the endocrine community.