PMID- 34801515 OWN - NLM STAT- MEDLINE DCOM- 20220110 LR - 20220110 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 288 DP - 2022 Jan 1 TI - Endrin potentiates early-stage adipogenesis in 3T3-L1 cells by activating the mammalian target of rapamycin. PG - 120151 LID - S0024-3205(21)01138-3 [pii] LID - 10.1016/j.lfs.2021.120151 [doi] AB - 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. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Seok, Jo Woon AU - Seok JW AD - Mo-Im Kim Nursing Research Institute, College of Nursing, Yonsei University, 03722 Seoul, Republic of Korea. FAU - Park, Jae Yeo AU - Park JY AD - Biobehavioral Research Center, College of Nursing Yonsei University, 03722 Seoul, Republic of Korea. FAU - Park, Hyun Ki AU - Park HK AD - Biobehavioral Research Center, College of Nursing Yonsei University, 03722 Seoul, Republic of Korea. FAU - Lee, Hyangkyu AU - Lee H AD - Mo-Im Kim Nursing Research Institute, College of Nursing, Yonsei University, 03722 Seoul, Republic of Korea; Biobehavioral Research Center, College of Nursing Yonsei University, 03722 Seoul, Republic of Korea. Electronic address: HKYULEE@yuhs.ac. LA - eng PT - Journal Article DEP - 20211118 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Insecticides) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (Akt1 protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - OB9NVE7YCL (Endrin) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/*cytology/drug effects/metabolism MH - *Adipogenesis MH - Animals MH - *Cell Differentiation MH - Endrin/*pharmacology MH - Gene Expression Regulation/*drug effects MH - Insecticides/pharmacology MH - Mice MH - Proto-Oncogene Proteins c-akt/genetics/*metabolism MH - TOR Serine-Threonine Kinases/genetics/*metabolism OTO - NOTNLM OT - Adipocyte OT - Adipogenesis OT - Endocrine-disrupting chemicals OT - Endrin OT - Lipogenesis OT - Obesity OT - mTOR signaling EDAT- 2021/11/22 06:00 MHDA- 2022/01/11 06:00 CRDT- 2021/11/21 20:38 PHST- 2021/06/03 00:00 [received] PHST- 2021/10/18 00:00 [revised] PHST- 2021/11/11 00:00 [accepted] PHST- 2021/11/22 06:00 [pubmed] PHST- 2022/01/11 06:00 [medline] PHST- 2021/11/21 20:38 [entrez] AID - S0024-3205(21)01138-3 [pii] AID - 10.1016/j.lfs.2021.120151 [doi] PST - ppublish SO - Life Sci. 2022 Jan 1;288:120151. doi: 10.1016/j.lfs.2021.120151. Epub 2021 Nov 18.