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

Abstract

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 IL-6, PGE, 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 F-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 inflammation-mediated IR. The results provide evidence that suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.

Analysis of Gut Microbiota in Rheumatoid Arthritis Patients: Disease-Related Dysbiosis and Modifications Induced by Etanercept

“…Moreover, we observed a decrease in Clostridiaceae upon ETN treatment which could be potentially beneficial since these bacteria were previously found enriched in patients with RA and IBD-associated arthropathy [ 35 ]. In patients treated with MTX, our analysis revealed a significant decrease in Enterobacteriales, whose lipopolysaccharides may contribute to inflammation [ 36 ], and which were associated with increased intestinal permeability [ 37 ], a condition that can be found in RA patients [ 38 ].…”

Effect of personalized moderate exercise training on Wistar rats fed with a fructose enriched water

“…Consequently, as C, FF, and ExFF group are not statistically different, we propose to invalidate IGT in C group with net glucose AUC. Nonetheless, IGT is not systematically observed in fructose fed model of MetS, and this IGT would be dependent of gender [ 6 ], time of regimen [ 43 , 44 ] and is improve with training [ 19 ].…”

The gut microbiota at the intersection of diet and human health

“…Experimental mice fed a high-fat diet (40 to 80% total caloric intake) exhibit decreases at the phylalevel in Bacteroidetes and increases in Firmicutes and Proteobacteria. These changes were observed in mice resistant to weight gain, implying a direct effect of dietary lipids on the microbiota (26,27). Germ-free (GF) mice are protected from the metabolic consequences of high-fat diets, suggesting that gut microbes may be important mediators of lipid-induced metabolic dysfunction (28).…”