Altered adipose lipid mobilization predicts long-term weight gain and impaired glucose metabolism

Factors predicting body weight gain and associated disturbed glucose metabolism remain to be established. Here we assessed the role of subcutaneous adipocyte lipid mobilization (lipolysis) in spontaneous long-term (>10 years) body weight changes. In two independent clinical cohorts we found that low stimulated lipolysis at baseline correlated inversely with body mass index changes over time. Disturbed lipolysis gave odds ratios of ≥4.6 for weight gain and ≥3.2 for development of insulin resistance and impaired fasting glucose/type 2 diabetes. Baseline adipose mRNA expression of a set of established lipolysis-regulating genes was lower in weight gainers. To obtain insights into the transcriptional fingerprint underlying the observed lipolysis differences, we performed gene microarray analyses of subcutaneous adipose tissue samples from 13 weight gaining and 25 weight stable women available at baseline