Fig. 6: A hypothetical model: the dual role of DNA damage response in obesity.
From: The dual nature of DNA damage response in obesity and bariatric surgery-induced weight loss
Under excessive caloric intake, hypertrophic expansion of white adipose tissue leads to adipocyte dysfunction, necrosis and fibrosis leading to low-grade systemic inflammation. At the molecular level, we speculate that DNA damage accumulation, chronic DDR activation, cellular senescence and mitochondrial dysfunction in visceral adipocytes concur to the release of autocrine and paracrine signals. These signals contribute to the development of a senescence-associated secretory phenotype (SASP), which is a systemic maladaptive homeostasis. Within the bloodstream, PBMCs in their quiescent state accumulate DNA damage without DDR activation. Following massive weight loss post-bariatric surgery, PBMCs shift toward an active state, characterized by cell proliferation, DDR activation associated with DNA repair and recovery of mitochondrial homeostasis. This adaptive cell survival response potentially contributes to the beneficial health effects of bariatric surgery. M1, M2: macrophages 1 and 2.
