Fructose-induced Fatty Liver Disease Research Articles

Terminalia Sericea aqueous leaf extract protects growing wistar rats against fructose-induced fatty liver disease.

Background Terminalia sericea (T. sericea) is traditionally used to treat stomach ailments, infections, hypertension and diabetes mellitus. Previous in vitro studies have reported that T. sericea has lipolytic properties. This study interrogated the effects of T. sericea on linear growth, development of fatty liver disease, viscera morphometry and health of growing rats fed a 12% fructose solution (FS). Methods Thirty 21-day old male Wistar rat pups were randomly allocated to five treatments: group I - plain gelatine cubes (PGC) + plain tap water (PW), group II - 12% FS + PGC, group III - gelatine cubes containing fenofibrate (Feno) at a dose of 100 mg/kg body + FS, group IV - gelatine cubes containing the low dose (100 mg/kg body mass per day) of the T. sericea extract (TsL) + FS, group V - gelatine cubes containing the high dose (400 mg/kg body mass per day) of the T. sericea extract (TsH) + FS. Following 12 weeks of feeding, the rats were fasted overnight, euthanized and plasma and viscera harvested for analysis. Results Consumption of fructose resulted in significantly increased (p<0.05) liver lipid content and caused macrovesicular steatosis. The T. sericea extracts at 400 mg/kg per day suppressed the fructose-induced liver lipid accumulation and macrovesicular steatosis similarly to 100 mg/kg per day of Feno. Conclusions These findings suggest that the aqueous T. sericea leaf extract at 400 mg/kg per day could potentially protect against fructose-induced lipid accumulation as well as macrovesicular steatosis.

Lipocalin-2 in Fructose-Induced Fatty Liver Disease.

The intake of excess dietary fructose most often leads to non-alcoholic fatty liver disease (NAFLD). Fructose is metabolized mainly in the liver and its chronic consumption results in lipogenic gene expression in this organ. However, precisely how fructose is involved in NAFLD progression is still not fully understood, limiting therapy. Lipocalin-2 (LCN2) is a small secreted transport protein that binds to fatty acids, phospholipids, steroids, retinol, and pheromones. LCN2 regulates lipid and energy metabolism in obesity and is upregulated in response to insulin. We previously discovered that LCN2 has a hepatoprotective effect during hepatic insult, and that its upregulation is a marker of liver damage and inflammation. To investigate if LCN2 has impact on the metabolism of fructose and thereby arising liver damage, we fed wild type and Lcn2−/− mice for 4 or 8 weeks on diets that were enriched in fructose either by adding this sugar to the drinking water (30% w/v), or by feeding a chow containing 60% (w/w) fructose. Body weight and daily intake of food and water of these mice was then measured. Fat content in liver sections was visualized using Oil Red O stain, and expression levels of genes involved in fat and sugar metabolism were measured by qRT-PCR and Western blot analysis. We found that fructose-induced steatosis and liver damage was more prominent in female than in male mice, but that the most severe hepatic damage occurred in female mice lacking LCN2. Unexpectedly, consumption of elevated fructose did not induce de novo lipogenesis or fat accumulation. We conclude that LCN2 acts in a lipid-independent manner to protect the liver against fructose-induced damage.

High-Fructose Intake Impairs the Hepatic Hypolipidemic Effects of a High-Fat Fish-Oil Diet in C57BL/6 Mice

Overnutrition of saturated fats and fructose is one of the major factors for the development of nonalcoholic fatty liver disease. Because omega-3 polyunsaturated fatty acids (n-3fa) have established lipid lowering properties, we tested the hypothesis that n-3fa prevents high-fat and fructose-induced fatty liver disease in mice. Male C57BL/6J mice were randomly assigned to one of the following diet groups for 14 weeks: normal diet (ND), high-fat lard-based diet (HFD), HFD with fructose (HFD+Fru), high-fat fish-oil diet (FOD), or FOD+Fru. Despite for the development of obesity and insulin resistance, FOD had 65.3% lower (P<0.001) hepatic triglyceride levels than HFD+Fru, which was blunted to a 38.5% difference (P=0.173) in FOD+Fru. The lower hepatic triglyceride levels were associated with a lower expression of lipogenic genes LXRα and FASN, as well as the expression of genes associated with fatty acid uptake and triglyceride synthesis, CD36 and SCD1, respectively. Conversely, the blunted hypotriglyceride effect of FOD+Fru was associated with a higher expression of CD36 and SCD1. During overnutrition, a diet rich in n-3fa may prevent the severity of hepatic steatosis; however, when juxtaposed with a diet high in fructose, the deleterious effects of overnutrition blunted the hypolipidemic effects of n-3fa.

PP-047 Effect of rosiglitazone on hepatic oxidative stress in fructose-induced fatty liver disease

PP-047 Effect of rosiglitazone on hepatic oxidative stress in fructose-induced fatty liver disease

Therapeutic interventions for fructose-induced fatty liver disease are premature

Therapeutic interventions for fructose-induced fatty liver disease are premature

Fructose takes a toll

Fructose takes a toll

Fructose-Induced Fatty Liver Disease

The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet (FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (+198%) and hepatic cholesterol (+89%), but a decrease in hepatic phospholipids (-36%), hypertriglyceridemia (+223%), and hypertension (+15%), without increase in HIC. Amlodipine reduced blood pressure (-18%), plasma triglycerides (-12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (-24%), plasma triglycerides (-36%), hepatic triglycerides (-51%), and hepatic macrovesicular fat (-51%), but increased HIC (+23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (-49%), hepatic triglycerides (-78%), hepatic macrovesicular fat (-90%), and blood pressure (-11%). We conclude that FED rats can be a suitable model for human NAFLD. Drugs administered to treat various aspects of the metabolic syndrome could have hepatic effects. An increase in HIC in rats with NAFLD could be associated with increased hepatic fibrosis.