UNACYLATED GHRELIN PLASMA LEVELS ARE LOWER AND PREDICT 5-YEAR LOW MUSCLE MASS IN ELDERLY OBESE SUBJECTS

Abstract

Aging-associated skeletal muscle loss may be paralleled by increased fat mass, both contributing to frailty and related healthcare and social costs. In general population cohorts, unacylated ghrelin (UnAG) plasma levels, an emerging modulator of skeletal muscle metabolism with potential muscle-anabolic actions, decrease in overweight-obese subjects [body mass index (BMI)> 25 kg/m2]. Potential associations between UnAG, overweight-obesity and muscle mass (MM) in elderly humans are currently unknown. In 450 elderly individuals (age>65y; M/F: 179/271) from the North-East Italy MoMa population study we investigated potential associations between ghrelin profile [total (TG), acylated (AG) and unacylated hormone (UnAG)] and body mass index (BMI). MM index (MM/m2) was measured in 133 subjects (M/F: 72/81) by bioelectrical impedance analysis after 5 years. Low MM-index cut-off was defined as two standard deviation lower than average MM-index in young (18-39) reference subjects from the same population. In elderly subjects, UnAG was lower (p<0.01) in overweight-obese compared to lean. Multiple regression analysis showed that UnAG was associated (P<0.01) with BMI independently of potential confounders such as gender, metabolic and inflammatory markers. In logistic regression analysis, lower basal UnAG predicted (p<0.05) low MM-index independently of gender, BMI and metabolic confounders. In elderly subjects from a North-East Italy general population cohort, unacylated ghrelin levels are lower in overweight-obese individuals and predict 5-year muscle mass independently from BMI. The present results suggest that lower UnAG may contribute to lower muscle mass in obese elderly individuals.