Toll-like Receptor 4 Mediates Fat, Sugar and Umami Taste Preference, and Food Intake and Body Weight Regulation

OBJECTIVE: Immune and inflammatory pathways play important roles in the pathogenesis of metabolic disorders. In the present study we investigate the role of TLR4 in orosensory detection of dietary lipids and sugars. METHODS: Taste preferences of TLR4 knockout (KO) and wild type (WT) male mice under standard, and high fat and high sugar diets were assessed with 2-bottle tests. Gene expression of taste signaling molecules was analyzed in the tongue epithelium The role of TLR4 in food intake, and weigh gain was investigated in TLR4 KO and WT mice fed a high fat and high sugar diet for 12 weeks. RESULTS: Compared to WT mice TLR4 KO mice showed reduced preference for lipids, sugars, and umami in 2-bottle preference test. The altered taste perception was associated with decreased levels of key taste regulatory molecules in the tongue epithelium. TLR4 KO mice on a high fat and high sugar diet consumed less food and drink, resulting in diminished weight gain. CONCLUSIONS: TLR4 signaling promotes ingestion of sugar and fat by a mechanism involving increased preference for such obesogenic foods.