MON-666 TRPA1 Modulation of Food Intake and Energy Balance in Obesity: Implications for Weight Regulation

Abstract Disclosure: C.D. Sua-Cespedes: None. L.M. Vasconcelos: None. J.S. Braulino: None. G. Zanetti: None. M. Silva: None. J.T. Lacerda: None. A.M. Castrucci: None. Food intake and energy expenditure regulation are therapeutic approaches for obesity. This complex process is governed mainly by the neuroendocrine system, with key modulators such as ghrelin, leptin, pro-opiomelanocortin (POMC), and corticotropin-releasing hormone (CRH). Although it is described that TRP channels could modulate food intake by influencing the hypothalamic neural circuits, there is not enough evidence describing the possible role of TRPA1 in this process. Three-month-old male C57BL/6J (WT) and Trpa1-/- (KO) mice were acclimated for two weeks in thermoneutrality (30±1°C), under a 12:12 light/dark photoperiod (lights on at 7 AM, ∼600 lux). After, animals were single-housed, kept at thermoneutrality or room temperature RT (22±1°C), and received a chow diet CD (3.8 kcal/g, 50g/kg fat) or high-fat diet HFD (5.3 kcal/g, 348 g/kg fat) during eight weeks. The animals were euthanized (CEUA-IBUSP 373/2021) at 9 AM, and blood and hypothalamic samples were collected. Blood was centrifuged for 10 min at 2000 x g at 4°C and then leptin was quantified in the serum; the gene expression of ghrelin and its receptor (Ghrl and Ghsr), leptin receptor (Lepr), Crh, Pomc, Trpa1, and Trpv1 was analyzed in the hypothalamus. There were no differences in weight between genotypes or temperatures when animals were fed CD. However, the food intake was higher in WT mice at RT and both Trpa1-/- groups, maybe as a physiological compensation for the temperature below the thermoneutrality zone and/or the lack of this channel. HFD WT mice developed a higher level of obesity (in both temperatures) than KO animals. Even with these differences in weight, all the obese animals had identical food intake. The HFD groups at RT showed an increase in hypothalamic ghrelin compared to their respective controls at 30°C. Only HFD Trpa1-/- mice at 22°C showed higher Ghsr mRNA content when compared to HFD WT at the same temperature. The leptin levels were higher in HFD WT animals than in CD WT mice and HFD Trpa1-/- animals at both temperatures. There were no significant differences in the hypothalamic Lepr mRNA among groups. HFD Trpa1-/- mice at 22°C showed a marked increase of Crh expression compared to KO mice at 30°C. Also, this group showed higher Pomc transcripts in comparison to KO animals in thermoneutrality and HFD WT mice at RT. In the CD groups, the WT animals expressed higher Pomc levels than their counterparts at 30°C. Interestingly, in the absence of TRPA1, the HFD KO animals at RT showed increased Trpv1 mRNA in comparison to their respective controls. Our data provide evidence that TRPA1 is a novel player in central food intake, energy expenditure, and weight regulation (especially at 22°C) in diet-induced obesity models. Presentation: Monday, July 14, 2025