Feeding a corn oil/sucrose-enriched diet enhances steatohepatitis in sedentary rats

Abstract

The current study investigated the combined effects of feeding a high-fat/high-sucrose (HF/HS) diet to rodents rendered sedentary via hindlimb unloading (HU). For 3 wk before HU, male Wistar rats were fed chow or a diet in which 32% of calories were derived from corn oil fat and 48% of calories from sucrose. Feeding continued during an additional 3-wk period of HU. Subsequently, blood samples were collected for determination of circulating leukocyte counts, insulin levels, and portal vein endotoxin. Inflammation, necrosis, and steatosis were assessed in formalin-fixed liver sections. No biochemical or histological evidence of injury was observed in control rats fed chow or HF/HS. HU increased circulating neutrophils and resulted in hyperinsulinemia. Mild hepatic fat accumulation and minimal focal necroinflammation were observed in this group. Feeding HF/HS during HU exacerbated hyperinsulinemia, hepatic steatosis, Kupffer cell content, and cytokine expression. Significant portal endotoxemia was noted in HU rats but was not influenced by HF/HS diet. On the other hand, feeding HF/HS significantly enhanced lipid peroxidation end products in liver of HU rats by approximately threefold compared with chow-fed rats. In summary, these findings demonstrate that feeding a high-calorie diet potentiates steatosis and injury in sedentary HU rats. Mechanisms underlying enhanced injury most likely involved lipid peroxidation. Importantly, these findings suggest that dietary manipulation combined with physical inactivity can be used to model steatohepatitis.

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“…Diets that were enriched with comparable amount of glucose or glycerol did not produce any over hepatic pathology. Surprisingly, in the studies presented in Table 4, steatosis was not always correlated with the presence of sucrose in the diet [20,59]. More studies are therefore needed to clarify the possible links between lipids and carbohydrates in NASH pathogenesis.…”

Western diet enhances hepatic inflammation in mice exposed to cecal ligation and puncture

“…All reactions were performed in duplicate using an Applied Biosystems 7500 PCR System and raw data were analyzed using the Applied Biosystems Prism Sequence Detection 1.9.1 software. The amount of mRNA relative to the 18s subunit was calculated using the comparative C t (ΔΔC t ) method as described previously [17]. …”

Leptin Induces an Inflammatory Phenotype in Lean Wistar Rats

“…Raw data were analyzed using the ABI Prism Sequence Detection 1.9.1 software. The relative amount of mRNA was calculated using the comparative threshold cycle (C t ) method as described previously [11]. …”