福赛坦菌激活舌背黏膜上皮细胞ERK通路导致脂味觉减退和成年“追赶肥”的机制研究

成年低营养水平者若营养快速大幅提升可导致“追赶肥”，这是肥胖相关疾病高发的重要原因之一。我们研究了舌背福赛坦菌定植可诱导脂味觉减退和成年“追赶肥”，但其机制尚待探究。进一步研究提示舌背黏膜上皮细胞ERK通路激活和角化增加，可能在脂味觉减退中起关键作用。本研究提出：福赛坦菌激活舌背黏膜上皮细胞ERK通路，诱导上皮过度角化，阻碍脂质与其受体结合；激活味蕾细胞ERK通路，竞争性抑制脂肪酸激活该通路，导致脂味觉减退和成年“追赶肥”。我们拟动态观察成年“追赶肥”大鼠舌背福赛坦菌定植、黏膜上皮细胞ERK通路和脂味觉改变；以福赛坦菌感染和甲硝唑干预大鼠福赛坦菌舌背定植，确证其对上述变化和代谢特征的影响；进而对舌背黏膜上皮细胞在体内以ERK通路抑制剂、体外以福赛坦菌等干预，验证福赛坦菌经激活舌背黏膜上皮细胞ERK通路导致脂味觉减退和成年“追赶肥”，并初步阐明其机制，为我国肥胖相关疾病精准防控提供新思路。

Rapid nutritional promotion after undernutrition in adults motivates catch-up fat, which is considered to be an important causative factor in the high incidence of obesity-related diseases in China. We found that the Tannerella forsythia in dorsal tongue surface induced fat taste perception impairment and adult catch-up fat, but the mechanism is unclear. Our further research revealed that activation of the ERK pathway in epithelial cells of dorsal tongue and increases in lingual keratosis were likely to play a crucial role in reducing perception of fat taste. Thus, we hypothesize that Tannerella forsythia induces fat taste perception impairment and adult catch-up fat by activating ERK pathway in epithelial cells of dorsal tongue and taste bud cells. The detailed mechanism is that the ERK pathway upregulation in epithelial cells of dorsal tongue results in lingual hyperkeratosis, consequently blocking the binding of lipids to their receptors, and the upregulation of ERK pathway in taste bud cells competitively inhibits fatty acid stimulated ERK pathway activation. We intend to investigate the dynamic changes of Tannerella forsythia colonization, activation of ERK pathway in epithelial cells of dorsal tongue and fat taste perception. We also plan to explore the effects of the Tannerella forsythia colonization on ERK pathway activation in epithelial cells of dorsal tongue, fat taste perception and metabolic profiles, as well as the mechanism of Tannerella forsythia inducing fat taste perception impairment and adult catch-up fat. This study will shed new light on the strategy for the precise prevention and intervention of obesity-related diseases in China.