Bariatric surgery and diet-induced long-term caloric restriction protect subcutaneous adipose-derived stromal/progenitor cells and prolong their life span in formerly obese humans

Abstract

A key effect of prolonged reducing diets and bariatric surgeries in formerly obese people is long-term caloric restriction (CR). The analysis of the impact of these interventions on specific tissues will contribute to a better understanding of their mechanisms of action. The physiological functions of subcutaneous white adipose tissues are mainly fulfilled by adipocytes arising out of adipose-derived stromal/progenitor cells (ASCs), which are crucial for adipose tissue homeostasis. In the present study we analyzed ASC from age-matched long-term calorically restricted formerly obese (CRD), obese (OD) and normal weight donors (NWDs). We demonstrate that ASC derived from CRD has a significant longer replicative lifespan than ASC isolated from OD and NWD. This correlated with strongly reduced DNA-damage and improved survival of the CRD ASC, both are hallmarks of CR. The adipogenic capacity was significantly lower in ASC derived from CRD than that from OD, as shown by reduced expression of the adipogenic key regulator PPARγ2 and the differentiation marker FABP4. The adipogenic capacity of ASCs from CRD and NWD differed only slightly. In conclusion, we provide evidence that bariatric surgery and diet-induced long-term CR substantially reprogram ASCs in formerly obese humans, comprising reduced DNA-damage, improved viability, extended replicative lifespan and reduced adipogenic differentiation potential.

Keywords: Adipose-derived stem cells; Caloric restriction; DNA damage; Humans; Senescence; Survival.