Chronic Stress Potentiates High Fructose–Induced Lipogenesis in Rat Liver and Kidney

Scope Intake of fructose‐sweetened beverages and chronic stress (CS) both increase risk of cardiometabolic diseases. The aim is to investigate whether these factors synergistically perturb lipid metabolism in rat liver and kidney. Methods and results Fractional de novo lipogenesis (fDNL), intrahepatic‐ and intrarenal‐triglycerides (IHTG and IRTG), de novo palmitate (DNPalm) content, FA composition, VLDL‐TGs kinetics, and key metabolic gene expression at the end of the feeding and non‐feeding phases in rats exposed to standard chow diet, chow diet + CS, 20% liquid high‐fructose supplementation (HFr), or HFr+CS are measured. HFr induces hypertriglyceridemia, up‐regulates fructose‐metabolism and gluconeogenic enzymes, increases IHTG and DNPalm content in IHTG and IRTG, and augments fDNL at the end of the feeding phase. These changes are diminished after the non‐feeding phase. CS does not exert such effects, but when combined with HFr, it reduces IHTG and visceral adiposity, enhances lipogenic gene expression and fDNL, and increases VLDL‐DNPalm secretion. Conclusion Liquid high‐fructose supplementation increases IHTG and VLDL‐TG secretion after the feeding phase, the latter being the result of stimulated hepatic and renal DNL. Chronic stress potentiates the effects of high fructose on fDNL and export of newly synthesized VLDL‐TGs, and decreases fructose‐induced intrahepatic TG accumulation after the feeding phase. High‐fructose supplementation increases plasma triglycerides (TGs) and decreases VLDL clearance, stimulates fractional de novo lipogenesis (fDNL) and increases de novo palmitate content, and stimulates both storage of TGs in the liver (IHTG) and VLDL‐TG secretion after the feeding phase. Stress potentiates the effects of fructose on fDNL, increases expression of lipogenic genes, and redirects the export of newly synthesized palmitate as VLDL‐TG.