Adipose–muscle crosstalk during the menopausal transition: mechanistic links to sarcopenic obesity in midlife women

Midlife represents a biological “phenotype transition” for women, during which sarcopenic obesity risk can rise despite stable BMI. Evidence anchored to the STRAW + 10 framework suggests that the interval surrounding the final menstrual period is an acceleration window for fat gain and centripetal/ectopic redistribution, creating an “invisible remodeling” trajectory that may increase the risk of developing sarcopenic obesity, which is not captured by routine anthropometrics. We synthesize mechanisms linking menopausal biology to increased risk of sarcopenic obesity: obesity-driven inflammation, adipokine dysregulation, and lipotoxic flux that impair insulin–AKT signaling and metabolic flexibility, coupled with reduced contractile/endocrine muscle output that worsens adipose phenotype. A key mediator is myosteatosis, comprising intramyocellular lipid and intermuscular adipose tissue, which can reduce specific force and manifest as dynapenia even when muscle size is preserved. Scalable monitoring of muscle quality using ultrasound echo intensity may complement CT/MRI in midlife practice. Estrogen withdrawal may further amplify energetic and regenerative vulnerability via ERα-related mitochondrial quality control and satellite-cell support, although menopause-stage human longitudinal data remain limited. In the GLP-1 era, lean mass loss during weight reduction and rapid regain after withdrawal strengthen the case for a function-first strategy integrating progressive resistance training and per-meal protein dosing/distribution. Standardized, menopause-calibrated sarcopenic obesity definitions and cohorts integrating strength, muscle quality, and ectopic fat are key priorities for prevention.