Dietary fat stimulates development of NAFLD more potently than dietary fructose in Sprague–Dawley rats

Abstract

BackgroundIn humans and animal models, excessive intake of dietary fat, fructose and cholesterol has been linked to the development of non-alcoholic fatty liver disease (NAFLD). However, the individual roles of the dietary components remain unclear. To investigate this further, we compared the effects of a high-fat diet, a high-fructose diet and a combination diet with added cholesterol on the development of NAFLD in rats.MethodsForty male Sprague–Dawley rats were randomized into four groups receiving either a control-diet (Control: 10% fat); a high-fat diet (HFD: 60% fat, 20% carbohydrate), a high-fructose diet [HFr: 10% fat, 70% carbohydrate (mainly fructose)] or a high-fat/high-fructose/high-cholesterol-diet (NASH: 40% fat, 40% carbohydrate (mainly fructose), 2% cholesterol) for 16 weeks.ResultsAfter 16 weeks, liver histology revealed extensive steatosis and inflammation in both NASH- and HFD-fed rats, while hepatic changes in HFr-rats were much more subtle. These findings were corroborated by significantly elevated hepatic triglyceride content in both NASH- (p < 0.01) and HFD-fed rats (p < 0.0001), elevated hepatic cholesterol levels in NASH-fed rats (p < 0.0001), but no changes in HFr-fed rats, compared to Control. On the contrary, only HFr-fed rats developed dyslipidemia as characterized by higher levels of plasma triglycerides compared to all other groups (p < 0.0001). Hepatic dysfunction and inflammation was confirmed in HFD-fed rats by elevated levels of hepatic MCP-1 (p < 0.0001), TNF-alpha (p < 0.001) and plasma β-hydroxybutyrate (p < 0.0001), and in NASH-fed rats by elevated levels of hepatic MCP-1 (p < 0.01), increased hepatic macrophage infiltration (p < 0.001), and higher plasma levels of alanine aminotransferase (p < 0.0001) aspartate aminotransferase (p < 0.05), haptoglobin (p < 0.001) and TIMP-1 (p < 0.01) compared to Control.ConclusionThese findings show that dietary fat and cholesterol are the primary drivers of NAFLD development and progression in rats, while fructose mostly exerts its effect on the circulating lipid pool.

Lactobacillus plantarum bacteriocin is associated with intestinal and systemic improvements in diet-induced obese mice and maintains epithelial barrier integrity in vitro

“…non-alcoholic fatty liver disease, 30 were similarly reduced with the administration of either L. plantarum strain.…”

The Impact of Nutrition and Environmental Epigenetics on Human Health and Disease

“…Nonalcoholic steatohepatitis (NASH), a form of NAFLD, is characterized by lipid accumulation in hepatocytes, inflammatory cell infiltrates, oxidative stress, and fibrosis and can lead to cirrhosis or hepatocellular carcinoma. The effects of a Western diet [ 41 ] or a high fat diet [ 42 ] on NAFLD development has been investigated in rodents. The risk of NAFLD may increase through an imbalance in fatty acids (FAs) in the Western diet.…”

Opuntia cladode powders inhibit adipogenesis in 3 T3-F442A adipocytes and a high-fat-diet rat model by modifying metabolic parameters and favouring faecal fat excretion

“…HFD causes hepatic inflammation and steatosis, which can further lead to non-alcoholic steatohepatitis and non-alcoholic fatty liver disease (NAFLD) [28]. To evaluate the potential toxicity of HFD and OCP supplementation, serum markers for liver injury and liver TG content were measured in our rat model.…”