Long-term high-fructose high-fat diet feeding elicits insulin resistance, exacerbates dyslipidemia and induces gut microbiota dysbiosis in WHHL rabbits

• Published in: PloS one Vol. 17; no. 2; p. e0264215
• Main Authors: Moughaizel, Michelle, Dagher, Elie, Jablaoui, Amin, Thorin, Chantal, Rhimi, Moez, Desfontis, Jean-Claude, Mallem, Yassine
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.02.2022; Public Library of Science (PLoS)
• Subjects: Abdomen; Animal models; Animals; Arteries; Atherosclerosis; Biology and Life Sciences; Cardiovascular diseases; Carotid arteries; Carotid artery; Cholesterol; Composition; Coronary vessels; Diabetes mellitus; Diagnosis; Diet; Diet, High-Fat - adverse effects; Digestive system; Digestive tract; Dysbacteriosis; Dysbiosis - etiology; Dysbiosis - metabolism; Dyslipidemia; Dyslipidemias - etiology; Dyslipidemias - metabolism; Engineering; Evaluation; Fasting; Fatty acids; Female; Food and Nutrition; Food science; Fructose; Gastrointestinal Microbiome; Glucose; Glucose tolerance; Health aspects; High fat diet; High Fructose Corn Syrup - adverse effects; Homeostasis; Hyperlipidemia; Insulin; Insulin Resistance; Intestinal microflora; Intestine; Laboratory animals; Laboratory testing; Life Sciences; Lipids; Lipoproteins; Low density lipoprotein; Male; Medicine and Health Sciences; Metabolic disorders; Metabolic syndrome; Metabolism; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Nutrition research; Obesity; Pathogenesis; Pharmacology; Plasma; Public health; Rabbits; Research and Analysis Methods; rRNA 16S; Triglycerides; Veterinary colleges; Veterinary medicine; France; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0264215

The metabolic syndrome (MetS) has become a global public health burden due to its link to cardiovascular disease and diabetes mellitus. The present study was designed to characterize the metabolic and cardiovascular disturbances, as well as changes in gut microbiota associated with high-fructose high-fat diet (HFFD)-induced MetS in Watanabe heritable hyperlipidemic (WHHL) rabbits. Twenty-one Watanabe rabbits were assigned to a control (n = 9) and HFFD (n = 12) groups, receiving a chow diet and a HFFD, respectively. During a 12-weeks protocol, morphological parameters were monitored; plasma fasting levels of lipids, glucose and insulin were measured and a glucose tolerance test (GTT) was performed. HOMA-IR was calculated. Cardiac function and vascular reactivity were evaluated using the Langendorff isolated heart and isolated carotid arteries methods, respectively. 16S rRNA sequencing of stool samples was used to determine gut microbial composition and abundance. HFFD-fed Watanabe rabbits exhibited increased fasting insulin (p < 0.03, 12th week vs. Baseline), HOMA-IR (p < 0.03 vs. Control), area under the curve of the GTT (p < 0.02 vs. Control), triglycerides (p < 0.05, 12th week vs. Baseline), TC (p < 0.01 vs. Control), LDL-C (p < 0.001 vs. Control). The HFFD group also displayed a significant decrease in intestinal microbial richness, evenness and diversity (FDR < 0.001, FDR < 0.0001, FDR < 0.01, respectively vs. Control group) and an increase in its Firmicutes/Bacteroidetes ratio (R = 3.39 in control vs. R = 28.24 in the HFFD group) indicating a shift in intestinal microbial composition and diversity. Our results suggest that HFFD induces insulin resistance and gut microbiota dysbiosis and accentuates dyslipidemia; and that, when subjected to HFFD, Watanabe rabbits might become a potential diet-induced MetS animal models with two main features, dyslipidemia and insulin resistance.