High-fat diet-induced anorexia in rats: involving orosensory deficits, gastrointestinal dysfunction, intestinal taste receptor downregulation and dopamine signaling dysregulation.

OBJECTIVES

To explore how a high-fat diet (HFD) led to anorexia in rats via peripheral-central axis integrated dysfunction.

METHODS

Twenty male Sprague‒Dawley rats were randomly assigned to the control group (G1, standard chow; n = 10) or the high-fat diet group (G2; n = 10) for 27 days. Body weight and food consumption were recorded at regular intervals. The gastric residual rate (GRR) and small intestinal advancement rate (SIAR) were used to evaluate gastrointestinal motility. The circumvallate papillae (CVP), proximal jejunum and hypothalamus were collected postintervention. Analyses included analyses of CVP histology (H&E staining), taste receptor type 1 member expression (T1R1/T1R2/T1R3) and transient receptor potential melastatin 5 (TRPM5) through immunohistochemistry and quantitative real-time PCR (qPCR) and hypothalamic dopamine (DA) levels by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Total food intake (41.5% lower) and final body weight (21.8% lower) were significantly lower in the HFD group than in the control group. The morphology of CVP was significantly degenerated by HFD feeding, resulting in a 49.13% reduction in the taste bud count. Gastrointestinal dysfunction was evidenced by increased GRR and decreased SIAR. Although taste receptor expression in CVP remained unchanged, the proximaljejunal mRNA expression levels of T1R1, T1R3, and TRPM5 significantly decreased. Notably, the DA concentration in the hypothalamus was also significantly lower in HFD-fed rats than in control rats.

CONCLUSIONS

HFD consumption effectively induced anorexia in young rats, which was accompanied by gastrointestinal dysfunction, a reduction in taste buds, impaired gut-brain axis taste transduction and a suppressed central DA response. These results indicate that peripheral-central axis impairment may be an important pathological phenomenon in HFD-induced anorexia.