Abstract
Introduction: Insulin resistance is prominent in overweight/obesity. We examined if insulin action in fat cells predicts the outcome of therapeutic weight loss. METHODS: We investigated 93 adult Swedes with overweight/obesity (body mass index, BMI, 29-50 kg/m2) before and after hypo-energetic high- or low-fat diet for 10 weeks. At baseline, overall insulin resistance (homeostasis model assessment, HOMA-IR) and insulin action on lipolysis and lipogenesis in isolated abdominal subcutaneous fat cells were determined. The participants were divided into tertiles based on their values for the cellular insulin action parameters. The relationship to weight loss parameters (fat mass index, fat free mass index, or BMI) was examined by analysis of variance. The influence of baseline age, sex, waist-to-hip ratio, physical activity, and BMI was investigated by analysis of covariance. Because the body weight loss (on average 8 kg) did not differ between the diets their respective data were combined. RESULTS: The sensitivity (half-maximum effective hormone concentration) of the anti-lipolytic effect of insulin correlated with loss of BMI, body weight, and fat mass index (F ≥ 3.1; p ≤ 0.0495). Body weight loss was about 30% greater in those with highest compared with lowest anti-lipolytic insulin sensitivity, and it was independent of the cofactors mentioned above (F = 8-9; p = 0.004-0.005). However, HOMA-IR, maximum insulin induced anti-lipolysis or lipogenesis and insulin sensitivity of lipogenesis did not associate with loss of BMI or fat mass index. CONCLUSION: A high anti-lipolytic insulin sensitivity in subcutaneous fat cells independently associates with pronounced weight loss following energy-restricted diet, whereas lipogenesis and overall insulin resistance are not related to weight change.
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