Endrin potentiates early-stage adipogenesis in 3T3-L1 cells by activating the mammalian target of rapamycin.

Abstract

Obesogens are a type of endocrine-disrupting chemicals (EDCs) that disrupt the human endocrine system, resulting in obesity and metabolic disease. Several obesogens, including bisphenol A, tolylfluanid, and some pesticides, have been identified and studied previously; however, the underlying molecular mechanisms by which obesogens interfere with adipogenesis and induce insulin resistance in adipocyte remain unknown. This study aims to determine which type of chemical is the most potent obesogen and to investigate its effect on adipogenesis-related gene expressions. 3T3-L1, a pre adipocyte cell line, was differentiated into mature adipocytes with either vehicle or various obesogens, including bisphenol A, tolylfluanid, and endrin, as well as corticosterone, at the same dose. Subsequently, intracellular and secreted triglyceride levels were measured, and the expression of genes and proteins involved in adipogenesis and lipogenesis was investigated. We found that endrin was the most potent regulator of adipogenic differentiation, as compared to tolylfluanid, bisphenol A, and corticosterone. Endrin increased intracellular and secreted triglyceride levels and enhanced the expression of adipogenic transcription factors as well as the terminal differentiation marker in a dose-dependent manner. During the early stages of differentiation, endrin enhanced mammalian target of rapamycin (mTOR) activity, which was suppressed by the pharmacological blockade of the protein kinase B-mTOR pathway, with repressed adipogenic differentiation. However, endrin did not change the expression levels of the downstream members of the mTOR signaling pathway or proteins related to lipolysis in response to insulin. Thus, we suggest that endrin potentiates early-stage adipogenic differentiation by activating the mTOR pathway.

• Authors: Jo Woon Seok, Jae Yeo Park, Hyun Ki Park, Hyangkyu Lee
• Journal: Life sciences (Life Sci) Vol. 288 Pg. 120151 (Jan 01 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34801515 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Insecticides
• mTOR protein, mouse
• Akt1 protein, mouse
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Endrin

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, drug effects, metabolism)
• Adipogenesis
• Animals
• Cell Differentiation
• Endrin (pharmacology)
• Gene Expression Regulation (drug effects)
• Insecticides (pharmacology)
• Mice
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• TOR Serine-Threonine Kinases (genetics, metabolism)