BACKGROUND:Excessive fructose intake causes metabolic syndrome and lipid accumulation in the kidney and leads to renal dysfunction and damage. Exercise (Ex) improves lipids regulation, but the mechanisms are remaining unclarified in the kidney.

METHODS:Male Sprague-Dawley rats were allocated to groups fed with CON or HFr diet. A part of rats in each group underwent treadmill exercise at an aerobic intensity for 12 weeks. Drug treatment was performed as the fenofibrate gavage during the last 4 weeks on HFr-fed rats. Renal function, histological changes and the expression of regulators involved in FA metabolism were assessed.

RESULTS:In CON-fed groups, Ex did not affect renal function or histology, and significantly increased the renal expression of FA b-oxidation regulators including acyl-CoA dehydrogenases (CADs), acyl-CoA oxidase (ACOX), peroxisome proliferator-activated receptorα (PPARα) and PPARγ-coactivator-1α (PGC-1α), and lipogenic factors including acetyl-CoA carboxylase (ACCα) and FA synthase (FAS), sterol regulatory element-binding protein 1c (SREBP1c). HFr caused albuminuria, lipid accumulation and renal pathohistological changes, which attenuated by Ex but not by fenofibrate. HFr decreased the renal expression of medium and short-chain CADs, PPARα, and increased the renal expression of lipogenesis enzymes including ACCα, FAS, and SREBP1c. Ex increased the expression of CADs, carnitine palmitoyltransferase type I (CPT-I), ACOX, PPARα, and PGC-1α anddecreased the expression of ACCα, FAS in the HFr-fed rats. The Ex-induced FA metabolism alteration was similar to those in the fenofibrate-treated group.

CONCLUSION:present study indicated that Ex enhances renal FA metabolism, which might protect the kidney in the lipids dysregulation diseases.

Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular triose phosphates proportionate to fructose intake. Triose phosphates are then processed into lactate, glucose and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion, however, escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose-rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglyceride concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re-synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole-body energy output related to a low physical activity on the other hand.