Endocrine Abstracts

Obesity is a chronic metabolic disease associated with important metabolic and inflammatory comorbidities, which can be reversed or improved after bariatric-surgery (BS). However, some underlying mechanisms, independent of weight-loss, are still unknown. In this context, dysregulations in the inflammasome, a multiproteic complex that promotes cytokine maturation and induces cellular pyroptosis, has been associated to the development/stage of some cancer-types and obesity. However, whether the dysregulation in the expression ofinflammasomecomponents is associated to morbid-obesity, BS, the modification of patient´ personal/environmental-behaviors, as well as to comorbidities reversal has not been yet explored. Therefore, the aim of this study was to determine the presence of addictive food behaviors (AFB) in obese patients undergoing BS, evaluate the changes in inflammasome components after BS, and analyze their causal relationships with the reversal of metabolic comorbidities. To that end, we took advantage of the emerging evidenceshowing that gene expression pattern of peripheral blood mononuclearcells (PBMCs) commonly reflects and accompany disease-characteristic expression patterns, and may thus serve as ageneral sentinel, biosensor and early indicator of the instaurationof metabolic disease to analyze the inflammasome components and associated inflammatory factors (n = 45; using a qPCR array based on Fluidigm technology) in the PBMCs of 22 patients before and 6-months after BS. Epidemiological/clinical/biochemical variables of the patients were recorded. AFB symptoms (evaluated using the Yale test) were observed in 18100% of patients. An overall dysregulation in inflammasome components, especially NOD-like receptors and cell-cycle and DNA-damage regulators, was observed in patients after BS. Interestingly, the molecular fingerprint of some inflammasome components (i.e. CXCL3/CCL8/TLR4/NLRC4/NLRP12) was able to perfectly discriminate between pre- and post-operative patients. Moreover, some alterations in the inflammasome were associated to certain basal metabolic comorbidities, including type-2 diabetes (CCL2/CXCR1/SIRT1), high blood pressure (AIM2/ASC/P2RX7) and dyslipidemia (CXCL3/NLRP7), as well as to the reversal of metabolic comorbidities after BS (IL18/NLRP12). Remarkably, the alteration in the inflammasome molecular profile after BS (especially cytokine/inflammation/apoptosis-related components) was also associated to some AFB. All these changes were independent of the surgical technique used. Altogether, BS induces a drastic alteration in the expression profile of inflammasome components of PBMCs, which is also modulated by personal/environmental behaviors. Moreover, the inflammasome molecular profile is associated to the presence and reversal of relevant metabolic comorbidities, suggesting that some inflammasome components might be used as novel diagnostic and therapeutic targets in morbid-obesity.

Fundings ISCIII (PI16-00264/PI17-02287), MINECO (FPU16/06190, FPU17/00263, FPU18/02485), Junta de Andalucía (PI-0038/2019, BIO-0139), CIBERobn.