Oral Prevotella induces fat taste impairment, visceral lipid accumulation and insulin resistance by downregulating Hedgehog signaling in taste buds

口腔普雷沃氏菌通过下调味蕾中的 Hedgehog 信号通路,诱发脂肪味觉障碍、内脏脂质积累和胰岛素抵抗。

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Abstract

BACKGROUND: Fat taste impairment has been implicated in visceral lipid accumulation and insulin resistance, with emerging evidence linking it to the oral microbiota. However, the role and mechanisms of the oral microbiota in this process remain unclear. OBJECTIVE: We aimed to explore the manifestations of Prevotella in fat taste, visceral lipid accumulation and insulin sensitivity, as well as to elucidate the mechanism involved. DESIGN: We characterized the oral microbiota in humans with fat taste impairment, visceral lipid accumulation and insulin resistance, as well as in catch-up fat rats. Fat taste sensitivity, serum biochemistry and tissue morphology were assessed in rats colonized orally with Prevotella to explore potential mechanisms. RESULTS: Reduced fat taste sensitivity correlated with visceral lipid accumulation and insulin resistance in both individuals and rats. Prevotella was enriched in individuals and rats with low fat taste sensitivity. Additionally, rats with visceral lipid accumulation and insulin resistance were associated with lower proliferation in taste buds and inhibition in Hedgehog (Hh) signaling. Prevotella colonization downregulated the Hh signaling, fat taste impairment, visceral lipid accumulation and insulin resistance, whereas Hh pathway agonist supplementation mitigated these effects. CONCLUSIONS: Oral microbiota and fat taste impairment are associated with visceral lipid accumulation and insulin resistance, and Prevotella may play a vital role in fat taste impairment, visceral lipid accumulation and insulin resistance by downregulating the Hh signaling in taste buds.

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