Intake of High Fat Diet leads to Over‐expression of CD36, QRFP and QRFPr in the Gustatory Neural Circuit
Authors: Primeaux Stefany D. 
Published: May 2022

Taste is a primary sensory modality that guides food preferences. Orosensory fat perception, which is mediated by lingual CD36, contributes to the intake and preference of dietary fat. Our previous studies indicate that feeding patterns differentially affect lingual CD36 mRNA expression and expression of homeostatic and hedonic markers in the brain. QRFP, an orexigenic peptide expressed primarily in the mediobasal hypothalamus (MBH), selectively increases the intake of high fat diet (HFD). The relationship between lingual CD36 and hypothalamic QRFP has yet to be investigated. Therefore, the goal of the current study was to conduct a time course analysis of continuous access to HFD on neural markers of food intake, including QRFP in the MBH and its receptor, QRFPr, in the nucleus accumbens (NAc). Male Sprague‐Dawley rats were fed a low fat diet (LFD, 10% kcal from fat) or HFD (55% kcal from fat) for 1 day, 3 days or 14 days. Body weight, food intake, and body adiposity were assessed. Real time PCR was used to determine the expression of CD36 mRNA on the circumvallate papillae of the tongue, expression of prepro‐QRFP, prepro‐NPY, and AgRP mRNA in the MBH, and dopamine receptor 1 (D1), 2 (D2) and QRFPr mRNA levels in the NAc. Rats fed HFD consumed more kilocalories than rats consuming the LFD, and gained more body adiposity, but not body weight, after 14 days of HFD intake. Lingual expression of CD36 mRNA was increased after 3 and 14 days of HFD intake. Intake of HFD increased hypothalamic expression of prepro‐QRFP mRNA but did not alter AgRP or prepro‐NPY mRNA levels. QRFPr expression in the NAc was significantly elevated by HFD intake, while D1 and D2 mRNA levels were differentially altered across days of HFD intake, with D1 levels decreasing after 14 days and D2 levels decreasing following 3 days access to HFD. Lingual CD36 mRNA was positively correlated with body weight gain and body adiposity and negatively correlated with AgRP mRNA levels. Hypothalamic prepro‐QRFP levels were positively correlated with kilocalorie intake. QRFPr mRNA levels in the NAc were positively correlated with body adiposity and negatively correlated with D1 and D2 mRNA levels. Prepro‐NPY and AgRP mRNA levels were negatively correlated with weight gain, body adiposity and QRFPr expression and AgRP levels were positively correlated with prepro‐NPY and D2 expression. Hypothalamic neuropeptides regulate food intake, particularly homeostatic eating. In this study, a time course analysis of HFD‐induced changes in gene expression suggest that while prepro‐NPY and AgRP levels were not altered, prepro‐QRFP mRNA levels were elevated. In the NAc, a brain region regulating hedonic eating, expression of D1 and D2, regulators of dopamine signaling, decreased, while QRFPr expression increased with HFD intake. These data, combined with the positive relationship between QRFP and kilocalories consumed and negative relationships between prepro‐NPY and AgRP and weight gain, suggest that CD36, QRFP and its receptor, QRFPr, may serve as positive regulators of caloric intake and weight gain by mediating the continued overconsumption of dietary fat.