| Autor: |
Panasevich MR; Research Service, Harry S. Truman Memorial Veterans Affairs Hospital , Columbia, Missouri.; Department of Nutrition and Exercise Physiology, University of Missouri , Columbia, Missouri., Meers GM; Research Service, Harry S. Truman Memorial Veterans Affairs Hospital , Columbia, Missouri.; Department of Nutrition and Exercise Physiology, University of Missouri , Columbia, Missouri.; Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri , Columbia, Missouri., Linden MA; Department of Nutrition and Exercise Physiology, University of Missouri , Columbia, Missouri., Booth FW; Department of Biomedical Sciences, University of Missouri , Columbia, Missouri., Perfield JW 2nd; Department of Nutrition and Exercise Physiology, University of Missouri , Columbia, Missouri.; Department of Food Science, University of Missouri , Columbia, Missouri., Fritsche KL; Department of Nutrition and Exercise Physiology, University of Missouri , Columbia, Missouri., Wankhade UD; Department of Pediatrics, Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences , Little Rock, Arkansas., Chintapalli SV; Department of Pediatrics, Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences , Little Rock, Arkansas., Shankar K; Department of Pediatrics, Arkansas Children's Nutrition Center, University of Arkansas for Medical Sciences , Little Rock, Arkansas., Ibdah JA; Research Service, Harry S. Truman Memorial Veterans Affairs Hospital , Columbia, Missouri.; Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri , Columbia, Missouri., Rector RS; Research Service, Harry S. Truman Memorial Veterans Affairs Hospital , Columbia, Missouri.; Department of Nutrition and Exercise Physiology, University of Missouri , Columbia, Missouri.; Division of Gastroenterology and Hepatology, Department of Medicine, University of Missouri , Columbia, Missouri. |
| Abstrakt: |
Pediatric obesity and nonalcoholic steatohepatitis (NASH) are on the rise in industrialized countries, yet our ability to mechanistically examine this relationship is limited by the lack of a suitable higher animal models. Here, we examined the effects of high-fat, high-fructose corn syrup, high-cholesterol Western-style diet (WD)-induced obesity on NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine. Juvenile female Ossabaw swine (5 wk old) were fed WD (43.0% fat; 17.8% high-fructose corn syrup; 2% cholesterol) or low-fat diet (CON/lean; 10.5% fat) for 16 wk ( n = 6 each) or 36 wk ( n = 4 each). WD-fed pigs developed obesity, dyslipidemia, and systemic insulin resistance compared with CON pigs. In addition, obese WD-fed pigs developed severe NASH, with hepatic steatosis, hepatocyte ballooning, inflammatory cell infiltration, and fibrosis after 16 wk, with further exacerbation of histological inflammation and fibrosis after 36 wk of WD feeding. WD feeding also resulted in robust cecal microbiota changes including increased relative abundances of families and genera in Proteobacteria ( P < 0.05) (i.e., Enterobacteriaceae, Succinivibrionaceae, and Succinivibrio) and LPS-containing Desulfovibrionaceae and Desulfovibrio and a greater ( P < 0.05) predicted microbial metabolic function for LPS biosynthesis, LPS biosynthesis proteins, and peptidoglycan synthesis compared with CON-fed pigs. Overall, juvenile Ossabaw swine fed a high-fat, high-fructose, high-cholesterol diet develop obesity and severe microbiota dysbiosis with a proinflammatory signature and a NASH phenotype directly relevant to the pediatric/adolescent and young adult population. |
