High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications.

Iona Lozano,Elisa Maillard,Séverine Sigrist,Michel Pinget,Stéphanie Dal,Claude Peronet,Nathalie Jeandidier,Elodie Seyfritz,Remmelt Van Der Werf,Eric Marchioni,William Bietiger

doi:10.1186/s12986-016-0074-1

Abstract

BackgroundAs a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is particularly used in prepared foods and carbonated beverages. We investigated the impact of regular consumption of fructose, in combination or not with fatty food, on the onset of metabolic syndrome and type 2 diabetes (T2D). We evaluated the metabolic, oxidative, and functional effects on the liver and blood vessels, both related to diabetes complications.MethodsHigh-fat diet (HFD), high-fructose beverages (HF) or both (HFHF) were compared to rats fed with normal diet (ND) for 8 months to induce T2D and its metabolic, oxidative, and functional complications. Metabolic control was determined by measuring body weight, fasting blood glucose, C-peptide, HOMA2-IR, leptin, and cholesterol; oxidative parameters were studied by lipid peroxidation and total antioxidant capacity in plasma and the use of ROS labelling on tissue. Histological analysis was performed on the liver and endothelial function was performed in main mesenteric artery using organ-baths.ResultsAfter 2 months, HFHF and HFD increased body weight, leptin, HOMA2-IR associated to steatosis, oxidative stress in plasma and tissues, whereas HF had only a transient increase of leptin and c-peptide. Only HFHF induced fasting hyperglycaemia after 6 months and persistent hyperinsulinaemia and fasting hyperglycaemia with complicated steatosis (inflammation and fibrosis) after 8 months. HFHF and HFD induced endothelial dysfunction at 8 months of diet.ConclusionsSix months, high fat and high carbohydrate induced T2D with widespread tissues effects. We demonstrated the role of oxidative stress in pathogenesis as well as in complications (hepatic and vascular), reinforcing interest in the use of antioxidants in the prevention and treatment of metabolic diseases, including T2D.

Highlights

As a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age
The present study demonstrates that only the combination of sugar and fat, present in beverage and diet (HFHF), allowed the development of type 2 diabetes (T2D) associated with long-term metabolic disorders such as maintenance of fasting hyperglycaemia, pre- and post-prandial hyperinsulinaemia, insulin resistance, glucose intolerance, and dyslipidaemia
Increased fat intake and Western diets have been linked to insulin resistance, impaired postprandial lipid metabolism, and the development or progression of non-alcoholic fatty liver disease (NAFLD)

Summary

Introduction

As a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is used commercially as a sweetening substitute (fructose corn syrup) for glucose or sucrose, in the preparation of desserts, condiments, and carbonated beverages [6]. It has been recently confirmed [7] that the consumption of high amounts of refined carbohydrates in food and beverage increases the risk of dyslipidaemia [8], obesity [4, 6], insulin resistance [9], and heart disease [10]. Chronic consumption of a Western diet, characterized by foods rich in sugar and abundant in total and saturated fat, has been suggested to play a role in the development of type 2 diabetes (T2D) [12]

Objectives

Methods

Results

Discussion

Conclusion