The potential protective effects of stearic acid against diet-induced metabolic syndrome in growing fructose-fed Sprague-Dawley rats

Abstract

Consumption of high-fructose and/or high-fat diet during the neonatal development phase increases de novo lipogenesis, which leads to the onset of metabolic dysfunction, including visceral obesity, non-alcoholic fatty liver disease and renal impairment. There is strong evidence that stearic acid has hypocholesterolaemia effects and thus its potential nutritional and health beneficial effects on the subsequent development of health outcomes associated with high-fructose and/or high-fat diet induced metabolic dysfunction necessitate further investigation. This interventional study aimed to investigate the impact of a diet enriched with stearic acid alone and/or combined with high-fructose on a) general metabolic health profile, b) non-alcoholic fatty liver disease, c) nephropathy and d) visceral and gastrointestinal tract morphometry, in growing female and male Sprague-Dawley rats. Eighty, 21-day old rats were randomly allocated to 5 treatment groups of 16 (8 males and 8 females) pups each and fed respective treatments for 13 weeks. Group I, (negative control), receiving standard rat chow and plain water to drink; group II, in which metabolic dysfunction was induced, rats were fed standard rat chow, 20% fructose solution; group III, served to investigate the prophylactic potential of stearic acid, rats were fed standard rat chow enriched with 3% stearic acid and 20% fructose solution to drink; group IV, rats were fed standard rat chow enriched with 3% stearic acid and plain water to drink to investigate the effects of stearic acid alone on metabolic health; group V, (positive control) in which fenofibrate was used for the prevention of metabolic dysfunction, rats were fed standard rat chow, 20% fructose solution to drink and fenofibrate (in gelatine cubes as a vehicle) at 100 mg/kg body mass. Groups I-IV rats all received plain gelatine cubes as vehicle control. Body mass was measured throughout the study. After the 13-week feeding period, rats were terminated and tissue samples collected. Fasting blood glucose, plasma total cholesterol, triglyceride, insulin, HOMA-IR, adiponectin concentrations and kidney-injury molecule-1 (KIM-1) a surrogate biomarker of kidney function were determined. Visceral and epididymal fat masses were measured to assess adiposity. Hepatic lipid content and fatty acid profile were determined. Liver and kidney histomorphometry were also performed. Feeding the rats with a stearic acid-enriched diet did not negatively affect their growth performance as all rats across dietary groups grew significantly during the feeding period with their ultimate body mass being significantly greater than their initial body mass (p <0.0001). v The high-fructose diet induced hypercholesterolemia, hypertriglyceridemia, hypoadiponectinemia, increased visceral adiposity, increased hepatic lipid content, caused micro-vesicular steatosis and hepatic inflammation and increased KIM-1 (p < 0.05) in rats. Stearic acid significantly increased plasma adiponectin (p < 0.001), decreased the high- fructose diet-induced hepatic lipid content (females) (p < 0.05), micro-vesicular steatosis (females) (p < 0.05), increase polyunsaturated fatty acids (females) (p < 0.05) and decrease trans fatty acids (males) (p < 0.05) as an intervention. However, stearic acid was ineffective in preventing (p > 0.05) high-fructose-induced increased cholesterol, triglycerides, visceral adiposity, hepatic inflammation and kidney damage marker KIM-1. Long bone parameters, fasting blood glucose, plasma insulin and insulin resistance, macro-vesicular steatosis, hypertrophy and kidney histomorphometry were not affected significantly (p > 0.05) by the dietary interventions. Furthermore, dietary treatments had no effect on gastrointestinal tract or visceral organ morphometry across treatment groups. Stearic acid alone significantly (p < 0.05) lowered cholesterol and triglycerides while increasing adiponectin levels compared to the negative control. The current data showed sex differences in response to stearic acid and high fructose diets and that stearic acid provided some protective effects against high-fructose-induced metabolic dysfunction, posing as a promising potential natural saturated fat in ameliorating poor metabolic outcomes associated with high-fructose diets. Stearic acid supplementation in the diet should be investigated further as a form of preventive therapy against high-fructose- induced metabolic dysfunction.