Neural markers of gustatory signaling are differentially expressed in male and female obesity-prone and obesity-resistant rats

The susceptibility to develop obesity may be mediated by a dysregulated perception of dietary fat, which is regulated by signals from the gustatory neural circuit, a complex neural network that begins at the tongue and continues to homeostatic and hedonic brain regions involved in eating behavior. The goal of the current study was to investigate sex differences in neural markers of gustatory signaling in obesity-prone and obesity-resistant rats consuming a high fat diet (HFD). Male and female obesity-prone, Osborne Mendel and obesity-resistant, S5B/Pl rats were fed a HFD (60% kcal from fat) for 7 weeks. HFD intake and body weight were measured. Real time PCR was used to determine mRNA expression of markers of fat sensing/signaling on the circumvallate papillae (CV) of the tongue, markers of homeostatic eating in the mediobasal hypothalamus (MBH) and markers of hedonic eating in the nucleus accumbens (NAc). Overall, males gained more weight than females and consumed more HFD. Obesity-prone rats gained more weight and consumed more HFD than obesity-resistant rats. Dietary fat is detected by the proposed fat taste receptor, CD36, on Type II taste receptor cells on the CV, which initiates a cascade of intracellular events culminating in the release of serotonin from Type III taste receptor cells and activation of the gustatory afferent nerve. In this study, expression of CD36, tryptophan hydroxylase 1 (TPH1) and serotonin transporter (SERT) mRNA were higher in females, compared to males, but did not differ between prone and resistant rats. The hypothalamus is a key region for the regulation of homeostatic eating. Under normal conditions, an equilibrium exists between the stimulation and suppression of food intake. In the current study, prepro-neuropeptide-Y (NPY) mRNA levels were higher in females, compared to males, and higher in obesity-resistant rats, compared to obesity-prone rats. Agouti-related peptide (AgRP) mRNA levels were higher in obesity-resistant rats, compared to prone rats, and mu opioid receptor (MOR) mRNA expression was higher in females, compared to males. To investigate altered markers of hedonic eating, the expression of genes involved in dopamine regulation within the NAc were assessed. Monoamine oxidase B (MOAB) mRNA expression was higher in males, compared to females and higher in obesity-resistant rats, compared to obesity-prone rats. A significant interaction between sex and strain was found for dopamine transporter (DAT) mRNA levels with obesity-prone female rats having higher expression than obesity-prone males. Both MOAB and DAT are involved in the termination of dopaminergic neurotransmission. Overall, these data suggest that signaling within the gustatory neural circuit is mediated by sex and the susceptibility to develop obesity. Differential regulation of these neural markers may regulate the overconsumption of dietary fat and lead to the development of obesity in males and females. This work was partially supported by the National Institutes of Health Pennington/Louisiana NORC Center Grant [P30DK072476] and the COBRE center grant [P20GM125002]. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.