Effect of Asprosin on Hypothalamic FTO, GLP-1R and MC4R Expression in Rats Fed a High Fat Emulsion

Abstract Asprosin (A) is a fasting-induced hormone involved in energy regulation, appetite control, and glucose metabolism, potentially through hypothalamic signaling pathways. This study aimed to investigate the effects of asprosin on hypothalamic FTO, GLP-1R, and MC4R expression and related metabolic parameters in rats fed a high fat emulsion (HF). Twenty-eight male Sprague Dawley rats were divided into four groups (n = 7 each): Control, A, HF, and HF + A. Rats in the HF and HF + A groups received an HF emulsion (10 mL/kg, orally) for 8 weeks, while asprosin (1 μg/kg/day, i.p.) was administered for 10 consecutive days in the A and HF + A groups. Body weight, BMI, Lee index, and liver index were recorded. Serum AST, ALT, ALP, TC, TG, HDL-C, LDL-C, glucose, insulin, and asprosin levels were measured. Hypothalamic mRNA expression of FTO, GLP-1R, MC4R, cAMP/PKA, NPY, AgRP, POMC, CART, and Ptprd was evaluated by RT-qPCR. Histopathological examinations were performed on brain and adipose tissues. HF feeding significantly increased body weight, liver index, liver enzymes, glucose, insulin, HOMA-IR, and serum asprosin levels, while decreasing insulin sensitivity (p < 0.05). Similar alterations persisted in the HF + A group, whereas parameters in the A group were comparable to controls. FTO, cAMP/PKA, NPY, and AgRP expression increased, whereas POMC, CART, GLP-1R, and MC4R expression decreased in the HF and HF + A groups. Asprosin upregulated hypothalamic FTO and downregulated GLP-1R and MC4R, associated with increased cAMP/PKA-related gene expression, suggesting a potential association with orexigenic signaling under high-fat conditions.