In this cross-sectional study of 55 middle-aged women between 45 and 60 years of age, we hypothesized that postmenopausal women had an increased lipid deposition in liver and skeletal muscle compared with that of premenopausal women and that the increased ectopic lipid deposition in postmenopausal women was associated with increased insulin resistance. Thus, increased ectopic lipid deposition during the menopausal transition could be an important mechanistic link between the fat depot changes and the increased incidence of insulin resistance seen after menopause however, this link has yet to be investigated. Furthermore, one study found an increased incidence of nonalcoholic fatty liver disease (NAFLD) in older women compared with younger women ( 16), all in all suggesting a role for female sex hormones in ectopic lipid deposition. Young men show increased lipid deposition in liver and skeletal muscle compared with young women ( 12, 13), and oophorectomized rodents show increased lipid deposition in liver and skeletal muscle compared with sham animals ( 14, 15).
Increased visceral fat mass results in a spillover of excessive amounts of lipids and production of inflammatory cytokines ( 9) promoting ectopic lipid deposition and lipotoxicity in liver and skeletal muscle and ultimately leading to insulin resistance ( 10, 11). In general, increasing gluteofemoral fat mass is associated with improved metabolic health ( 7), whereas expansion of the visceral fat mass leads to dysfunctional adipose tissue, including adipocyte hypertrophy, macrophage infiltration, and impaired insulin signaling ( 8). Through the menopausal transition, the body composition changes from favoring gluteofemoral to truncal fat deposition, particularly visceral fat accumulation ( 5, 6). The increased disease burden after the menopausal transition therefore is a major health concern. In modern society, women live more than one-third of their lives after menopause. Menopause defines the end of women’s reproductive phase and is associated with an increased occurrence of metabolic disease, including metabolic syndrome ( 2), diabetes ( 3), and cardiovascular disease ( 4). The prevalence of obesity and metabolic disease has reached epidemic proportions and is a major health concern in the Western world ( 1).