Cellular Mechanisms Driving Sex Differences in Adipose Tissue Biology and Body Shape in Humans and Mouse Models

Abstract

Sex differences in adipose tissue distribution and the metabolic, endocrine, and immune functions of different anatomical fat depots have been described, but they are incompletely documented in the literature. It is becoming increasingly clear that adipose depots serve distinct functions in males and females and have specific physiological roles. However, the mechanisms that regulate the size and function of specific adipose tissues in men and women remain poorly understood. New insights from mouse models have advanced our understanding of depot differences in adipose growth and remodeling via the proliferation and differentiation of adipose progenitors that can expand adipocyte number in the tissue or simply replace dysfunctional older and larger adipocytes. A limited ability of a depot to expand or remodel can lead to excessive adipocyte hypertrophy, which is often correlated with metabolic dysfunction. However, the relationship of adipocyte size and function varies by depot and sex. For example, femoral adipose tissues of premenopausal women appear to have a greater capacity for adipose expansion via hyperplasia and hypertrophy; although larger, these gluteal-femoral adipocytes remain insulin sensitive. The microenvironment of specific depots, including the composition of the extracellular matrix and cellular composition, as well as cell-autonomous genetic differences, influences sex- and depot-dependent metabolic and growth properties. Although there are some species differences, studies of the molecular and physiological determinants of sex differences in adipocyte growth and function in humans and rodents are both needed for understanding sex differences in health and disease.

The omentum of obese girls harbors small adipocytes and browning transcripts

“…Indeed, adolescence is considered a critical time for obesity development (41). Given the major sex differences in body fat distribution (42)(43)(44)(45) and higher prevalence rates of SO among females, we elected to study only girls.…”

Body composition in anorexia nervosa: Meta‐analysis and meta‐regression of cross‐sectional and longitudinal studies

“…Overall, the meta‐analyzed study sample was highly selected and biased as it comprised mostly European females aged between 14 and 31 years, emphasizing the urgent need for studies including diverse ancestries, such as Asia, South and Central America, and Africa. Females and males differ in body composition and metabolic characteristics (Karastergiou & Fried, ; Link & Reue, ), underscoring the need for more studies on males with AN. Our study selection was limited by the lack of control groups and underreported extensive sample overlap.…”

Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue

“…The metabolic properties of adipose tissue are influenced in a distinct depot-and sex-dependent manner (Karastergiou & Fried, 2017). Thus, adipose tissues from distinct depots may respond differently to exercise partly due to the sensitivity or rhythmicity of the response to various hormones, especially glucocorticoids, but also due to their intrinsic circadian gene expression profiles (Garaulet et al 2011;Lee et al 2014).…”