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Mechanistically different effects of fat and sugar on insulin resistance, hypertension and gut microbiota in rats

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Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to type-2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma interleukin-6, prostaglandin E2 and reduced levels of protective short-chain fatty acids without triggering hypertension. Increased populations of gut Enterobacteriales and Escherichia coli may contribute to systemic inflammation through the generation of lipopolysaccharides. Unlike fat, fructose induces increased levels of diacylglycerols (lipid mediators of IR) in the liver, urine F2-isoprostanes (markers of systemic oxidative stress) and uric acid, and triggers hypertension. Elevated populations of Enterobacteriales and E. coli were only detected in rats given an excess of fructose at the end of the study. Dietary fat and fructose trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade inflammation and late direct lipid toxicity, respectively; gut microbiota plays a role mainly in fat-induced IR; and hypertension is independent of inflammation55 mediated IR. The results provide evidence which suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.

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American Journal of Physiology, 2018, vol. 314, num. 6, p. E552-E563

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(c) American Physiological Society, 2018

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Articles publicats en revistes  (Enginyeria Química i Química Analítica)

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Mechanistically different effects of fat and sugar on insulin resistance, hypertension and gut microbiota in rats