Previous attempts to limit fat intake failed to reduce metabolic syndrome incidence, spotlighting excessive sucrose consumption phenomenon. Recent studies challenge the traditional belief, actually fructose is predominantly metabolized in the small intestine, not just the liver. Evidence supports sucrose overconsumption leads to hepatic lipid accumulation via gut microbiome modulation, but the mechanisms and prevention strategies remain unclear. This study investigates the impact of osmolytes inositol and taurine, which are abundant in citrus fruits and seafood respectively, on lipid metabolism in rats consuming excessive sucrose. Five-week-old male Wistar rats fed with control diet, high sucrose diet, and high sucrose diet with inositol or taurine for 28 days. High sucrose diet-induced accumulation of hepatic triglyceride level was reduced only by inositol. Both inositol and taurine decreased hepatic SREBP1, ChREBP, lipogenesis enzymes mRNA levels increased by a high sucrose diet. Taurine also significantly increased the fatty acid uptake major player CD36 mRNA levels in liver. Expression of genes related to fatty acid degradation and transport remained unchanged. In cecal microbiome, high sucrose diet groups showed a decrease in alpha diversity and diverged in beta diversity from the starch diet group, while inositol and taurine did not significantly affect these aspects. Ten bacterial features including genera such as Bacteroides, Parabacteroides, Odoribacter, Streptococcus, etc., were filtered out related to the ameliorative effects of inositol and taurine on lipid metabolism. Overall, both inositol and taurine modulated hepatic lipogenesis and microbiome. However, due to taurine's enhancement of fatty acid uptake, only inositol improved steatosis in high sucrose diet rats.
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