The Accumulation of Visceral Fat in Postmenopausal Women: The Combined Impact of Prenatal Genetics, Epigenetics, and Fat Depot Heterogeneity—A Descriptive Review
Authors: Zhang Zhongming , He Ziyi , Yang Huilun , Li Danxia , Duan Peipei , Wei Xiaomen 
Published: February 2025

Objective: This review aims to provide an overview of the factors contributing to central obesity, particularly in postmenopausal women, who are affected at a global rate of 26%. It emphasizes the heterogeneity of adipocytes, the impact of prenatal genetic factors, and the role of estrogenic neuroendocrine regulation. Additionally, the review explores the paradoxical functions of visceral fat and identifies the primary depots that may contribute to its overall function. Mechanism: Estrogen deficiency is a key factor in central adiposity among postmenopausal women, leading to a reduction in subcutaneous adipose tissue (SAT) and an increase in visceral adipose tissue (VAT) compared to premenopausal women. This deficiency deactivates pro-opiomelanocortin (POMC) neurons and steroidogenic factor-1 (SF1) neurons via estrogen receptor alpha (ERα), desensitizes vagal cholecystokinin-A (CCK-A) receptors, and hyperactivates the hypothalamic-pituitary-ovary (HPO) axis, resulting in increased food intake and decreased energy expenditure. The differences between VAT and SAT, such as expandability, anatomic location, free fatty acid (FFA) mobility, facilitate energy transfer from SAT to VAT, thereby contributing to central obesity. VAT also compensates for estrogen deficiency by releasing estradiol, inflammatory and anti-inflammatory adipocytokines, and increasing 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity, which potentiates glucocorticoid functions and ultimately leading to the development of metabolic syndromes. VAT is heterogeneous, including distinct depots such as mesenteric, gonadal, and perirenal fat. Mesenteric fat may play a significant role in body weight regulation and insulin resistance, while other fat depots interact more closely with surrounding organs to regulate various physiological functions. Understanding VAT heterogeneity is crucial for identifying adiposopathy markers associated with various metabolic syndromes. This knowledge can inform holistic, personalized therapeutic and bodybuilding approaches, helping patients to mitigate the risks associated with current hormone therapies. Findings in Brief: The ratio of SAT to VAT is shaped by a combination of prenatal genetics, neuroendocrine regulation, and postnatal epigenetic factors influenced by environmental energy availability and estrogen deficiency. VAT accumulation exhibits paradoxical roles, aiding adaption to energy surplus stress while simultaneously contributing to postmenopausal syndromes. Within VAT, heterogeneity exists, with mesenteric fat depots playing a key role in its overall function. Long-term protective strategies during the perimenopausal and menopausal periods may include energy restriction and the maintenance of normal estrogen levels. Personalized diets and estrogen supplementation hold promise in alleviating associated syndromes. Further exploration of the relationship between mesenteric fat, VAT accumulation, and menopausal syndromes could help clarify existing contradictory evidence and position mesenteric fat as a potential target for effective interventions aimed at alleviating postmenopausal symptoms with fewer side effects. Conclusions: Visceral fat accumulation in postmenopausal women is a consequence of energy stress due to estrogen deficiency, followed by the energy transfer from SAT to VAT. The heterogeneity of VAT suggests that its components may have different roles in body weight regulation. Mesenteric fat may play a major role among the depots.