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Updated: Feb 8, 2026

Robust Differentiation of Human iPSCs into a Pure Population of Adipocytes to Study Adipocyte-Associated Disorders

Robust Differentiation of Human iPSCs into a Pure Population of Adipocytes to Study Adipocyte-Associated Disorders

Published on: February 9, 2022

BPA代替物質のPPARγ結合および脂肪細胞分化への影響に関するメカニズム的洞察

Daniela Flores Gomez¹, Nikita Korpel¹, Marina Grimaldi²

¹Institute for Risk Assessment Sciences, Department of Population Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht 3584 CM, The Netherlands.

Environmental science & technology

|February 6, 2026

Abstract:

The obesity epidemic is increasingly linked to environmental factors like endocrine disrupting chemicals (EDCs). Bisphenol A (BPA), a known EDC, has been suspected to be linked to adiposity through activation of peroxisome proliferator activated receptor gamma (PPARγ), a key regulator of adipogenesis. Though many BPA alternatives have been introduced as substitutes, their effects on metabolic health remain unclear. This study aimed to investigate the mechanistic interactions of 11 BPA alternatives with PPARγ and their adipogenic potential. Using a PPARγ reporter assay, we assessed the binding affinity and activation potential of BPA alternatives, followed by X-ray crystallography of two potent activators, 4-benzyloxyphenyl 4-hydroxyphenyl sulfone (BPS4BE) and bisphenol PH (BPPH). Additionally, adipogenesis was assessed via a human mesenchymal stem cells (hMSCs) differentiation assay. Results revealed that the alternatives BPPH and BPS4BE potently activated PPARγ (BMD20 (μM): 0.23 and 0.34 respectively). Both significantly induced adipogenesis and a positive correlation was found between PPARγ activation and adipogenic differentiation. Crystallography revealed distinct binding modes for BPPH and BPS4BE compared to rosiglitazone, indicating partial agonism. These findings raise significant concerns about the safety of BPA alternatives and underscore the need for structure-based risk assessment to ensure safer substitutes.

キーワード:

X線結晶構造解析脂肪形成肥満ペルオキシソーム増殖剤活性化受容体ガンマ

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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance

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