TISSUE-SPECIFIC PROINFLAMMATORY PROFILE IN A TNFR1-DEFICIENT MOUSE MODEL OF DIET-INDUCED OBESITY

BARRERA FS ; GUZMAN FS; CHACON I DEL V; SANTILLAN LD; FORNES MW; RAMIREZ DC; GOMEZ MEJIBA SE

SAN JUAN

Congreso; SBC; 2023

Chronic dietary consumption of hypercaloric diets (HCD) is linked to systemic and tissue-specific inflammation. Many of the pro-inflammatoryexcess energy consumption effects are mediated by the interaction between the tumor necrosis factor á (TNFá) and its cognate receptor (TNFR).Excess energy in the form of free fatty acids is known to activate toll-like receptor TLR2 and cause an inflammatory response in multipletissues. These changes can lead to NF-êB activation and thus increased expression of inflammatory biomarkers, such as inducible nitric oxide(iNOS) expression and neutrophilic inflammation. Neutrophils contain myeloperoxidase (MPO), which is an hemoprotein that uses H2O2 tooxidize chloride anions to HOCl, causing chlorination stress. In this study, we aimed to test whether chronic hypercaloric diet (HCD)consumption causes systemic, lung, liver, and adipose tissue inflammation in a TNFR1 (p55-/-) deficient C57BL6 mouse model of diet-inducedobesity. To achieve our goal, we fed 7-week-old males TNFR1-deficient mice a control diet (COD, rodent food, and tap water) or an HCD(22% bovine fat + 10% fructose in drinking water) for 24 weeks. Food, water, body weight, caloric intake, and insulin resistance were weeklymeasured. At the end of the dietary regimen, serum IL-6 and TNFá concentration—markers of systemic inflammation were measured byELISA. Moreover, nitrotyrosine—a marker of nitrosative stress, iNOS, MPO, TNF-á, IL-6, chlorotyrosine—a marker of neutrophilicinflammation content was measured by ELISA in lung, liver, and epididymal adipose tissue. Compared to the control diet, TNRF1-deficientmice fed an HCD showed a higher expression of IL-6 and TNFá concentration in serum. Whereas the lung tissue showed a higher content ofiNOS and MPO. However, the liver and epididymal adipose tissue of TNFR1 deficient mice fed an HCD showed no differences whencompared to mice fed a control diet. Data gathered from this study suggest that an excess energy balance in our TNFR1-deficient mouse modelof diet-induced obesity causes systemic and lung tissue inflammation, but does not cause changes in the inflammatory profile of either adiposetissue or liver. Overall, these findings warrant further mechanistic investigation that will provide important insights about the tissue-specificimpact of obesity in the absence of TNFá signaling. Supported by PICT2018-03435, PICT2021-0147 and PUE013