Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism

Nov 14, 2024Biochemical pharmacology

How GLP-1 and Estrogen Work Together to Control Fat Metabolism

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Abstract

Ovariectomy in female rats led to significant changes in metabolic parameters, including increased lipid catabolism and lipolysis in adipose tissue.

Ovariectomy increased lipid breakdown in perirenal adipose tissue and enhanced basal fat breakdown in subcutaneous adipose tissue.
Liraglutide treatment further increased stimulated fat breakdown in subcutaneous adipose tissue and the liver.
Distinct gene expression patterns were observed in the adipose tissue of ovariectomized rats compared to those treated with the GLP-1 receptor agonist.
Estrogen appears to play a critical role in regulating pathways linked to lipid and glucose metabolism.
The findings suggest complex interactions between GLP-1 and estrogen in metabolic regulation, indicating potential therapeutic synergies.

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Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinases. To investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen's pivotal role in these pathways, influencing genes involved in lipid metabolism regulation. Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2.

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Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism

Abstract

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