To better understand the contribution of the fat mass to the effects of long-term caloric restriction in humans, we compared adipokine profile and insulin sensitivity in long-term calorically restricted formerly obese women (CRW) subjected to different interventions, bariatric surgery, or reducing diet, with age- and BMI-matched obese (OW) and normal-weight women (NW) eating ad libitum. Our key findings are that despite a considerably stronger weight loss induced by bariatric surgery, both long-term caloric restriction interventions improved insulin sensitivity to the same degree and led to significantly lower retinol-binding protein-4 and interleukin-6 serum levels than in OW, suggesting that lowering of these two adipokines contributes to the improved insulin sensitivity. Moreover, serum leptin was considerably lower in CRW than in OW as well as in NW, suggesting that CRW develop hypoleptinemia.