Chronic High-Fat Diet Downregulates M3 Muscarinic and β1-Adrenergic Receptor mRNA Expression and Alters Submandibular Gland Histology in Wistar Rats.

Abstract

Introduction: A chronic high-fat diet (HFD) is associated with metabolic disturbances, inflammation, oxidative stress, and functional impairment in several organs. However, its effects on autonomic receptor expression and submandibular gland histology remain insufficiently understood. The submandibular gland contributes 65 to 75% of basal salivary secretion and is central to salivary function. This study aimed to investigate the effect of chronic HFD exposure on M3 muscarinic receptor and β1-adrenergic receptor mRNA expression, as well as histological changes, in the submandibular glands of Wistar rats.

Methods: This experimental study used a completely randomized design. Fourteen male Wistar rats were divided into two groups: a normal chow diet control group and an HFD group, with seven rats in each group. The HFD was administered for 21 weeks. Submandibular gland tissues were collected and analyzed for M3 muscarinic receptor and β1-adrenergic receptor mRNA expression using quantitative real-time polymerase chain reaction. Histological examination was performed using hematoxylin and eosin staining, and the mean number of secretory units per field of view was calculated. Data were analyzed using the Shapiro-Wilk normality test followed by an independent t-test.

Results: M3 muscarinic receptor mRNA expression was significantly lower in the HFD group than in the control group (0.189 ± 0.057 vs 0.483 ± 0.101; p < 0.001). β1-adrenergic receptor mRNA expression was also significantly reduced in the HFD group compared with the control group (0.067 ± 0.031 vs 0.169 ± 0.071; p = 0.008). Histological analysis showed that the mean number of secretory units per field of view was significantly lower in the HFD group than in the control group (9.84 ± 0.654 vs 13.52 ± 2.171; p = 0.007).

Conclusion: Chronic HFD exposure downregulated M3 muscarinic receptor and β1-adrenergic receptor mRNA expression and induced histological alterations in the submandibular glands of Wistar rats. These findings suggest that chronic HFD may affect salivary gland structure and autonomic regulation, providing a potential basis for salivary dysfunction and increased oral health risks. However, further studies incorporating direct functional assessments are needed to confirm its actual impact on saliva secretion.