UC Irvine

BACKGROUND: Weight changes after menopause contribute to cardiometabolic risk, yet hormonal determinants of long-term weight trajectories remain incompletely understood. Asprosin, a fasting-induced adipokine involved in hepatic gluconeogenesis and appetite regulation, has been associated with metabolic disease, although its prospective role in affecting weight change remains unknown. OBJECTIVES: This study aimed to examine whether plasma asprosin concentrations are directly and prospectively associated with changes in body weight and body composition among postmenopausal women. METHODS: In a case-control study of 4020 postmenopausal women (1987 newly developed/incident diabetes cases and 2033 matched controls) nested within the Women's Health Initiative, we prospectively evaluated participants' baseline plasma concentrations of asprosin in relation to 3-y changes in weight, measures of central obesity, and the risk of major weight gain or loss (≥7% of baseline weight). Associations were examined overall and stratified by baseline body mass index (BMI) or whether the participant developed diabetes during follow-up. Dual-energy X-ray absorptiometry-derived fat and lean mass were available for a subset of participants (n = 178). RESULTS: In the full cohort (n = 4020), baseline asprosin was not associated with 3-y weight change or changes in central adiposity. However, among matched controls with BMI <30 kg/m², participants in the highest asprosin quartile gained 1.61 kg less than those in the lowest quartile [adjusted β: -1.61; 95% confidence interval (CI): -2.69, -0.52; P-trend < 0.01] and had lower odds of major weight gain (adjusted OR: 0.57; 95% CI: 0.37, 0.88; P-trend < 0.01) and higher odds of major weight loss (adjusted odds ratio: 1.83; 95% CI: 1.10, 3.05; P-trend = 0.02). CONCLUSIONS: In this prospective study of postmenopausal women followed for 3 y, baseline asprosin concentrations were associated with weight change in apparently healthy women without diabetes or obesity.