Insulin resistance in NASH

Choudhury, Jayanta; Aj, Sanyal

doi:10.2741/1636

Cited by 45 publications

(29 citation statements)

References 75 publications

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“…No perfect theory exists for all its clinical manifestations [13,14] . At present, IR along with hepatocyte fatty degeneration is believed to be a key factor in the occurrence and development of fatty liver disease [15,16] . Research indicates [10] that IR exits in about 98% of patients with NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease

Wang¹,

Shi²,

Wang³

et al. 2009

WJG

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AIM:To evaluate the possible role of Tribble 3 (TRB3) in a rat model of non-alcoholic fatty liver disease (NAFLD) and its signal transduction mechanism.METHODS: T h i r ty S p ra g u e -D a w l e y ra t s w e r e randomized into three groups: normal control group, non-alcoholic fatty liver group A (fed on a highfat diet for 8 wk) and group B (fed on a high-fat diet for 16 wk). To determine the degree of hepatic steatosis in rats of each group, livers were stained with hematoxylin and eosin, and evaluated; realtime fluorescent quantitative reverse transcriptasepolymerase chain reaction was performed to measure the expression levels of TRB3 mRNA; and Western blotting analysis was done to determine the expression levels of protein kinase B (Akt) and phosphorylated protein kinase B (p-Akt-Thr308, p-Akt-Ser473). RESULTS:Hepatic steatosis was evident in both NAFLD groups: mild to moderate hepatic steatosis occurred in group A, mainly as mild steatosis. Moderate to severe hepatic steatosis occurred in group B, mainly as severe steatosis. The expression level of TRB3 mRNA in group B was significantly higher than in the control group (122.28 ± 95.37 vs 3.06 ± 2.33, P = 0.001) and group A (122.28 ± 95.37 vs 5.77 ± 4.20, P = 0.001). There was no significant difference in the CONCLUSION: TRB3 blocks insulin signaling by inhibiting Akt activation, which contributes to insulin resistance. It may be an important factor in the occurrence and development of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease

Wang¹,

Shi²,

Wang³

et al. 2009

WJG

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“…12 OSA is also independently associated with insulin resistance and type 2 diabetes mellitus in obese individuals, 2,44-46 and CIH exacerbates insulin resistance in obese rodents. 11 Because hepatic steatosis is a known consequence of insulin resistance, 16,47,48 a CIH-induced increase in insulin resistance in combination with oxidative stress may lead to NASH in obese patients with OSA and in obese mice exposed to CIH. However, our new findings indicate that, in the absence of obesity, CIH does not result in hyperinsulinemia and liver steatosis (Tables 1 and 2, Fig.…”

Section: Discussionmentioning

confidence: 99%

Chronic intermittent hypoxia predisposes to liver injury†

et al. 2007

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Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). OSA is associated with nonalcoholic steatohepatitis (NASH) in obese subjects. The aim of this study was to investigate the effects of CIH on the liver in the absence of obesity. Lean C57BL/6J mice (n ‫؍‬ 15) on a regular chow diet were exposed to CIH for 12 weeks and compared with pair-fed mice exposed to intermittent air (IA, n ‫؍‬ 15). CIH caused liver injury with an increase in serum ALT (224 ؎ 39 U/l versus 118 ؎ 22 U/l in the IA group, P < 0.05), whereas AST and alkaline phosphatase were unchanged. CIH also induced hyperglycemia, a decrease in fasting serum insulin levels, and mild elevation of fasting serum total cholesterol and triglycerides (TG). Liver TG content was unchanged, whereas cholesterol content was decreased. Histology showed swelling of hepatocytes, no evidence of hepatic steatosis, and marked accumulation of glycogen in hepatocytes. CIH led to lipid peroxidation of liver tissue with a malondialdehyde ( O bstructive sleep apnea (OSA) is characterized by recurrent collapse of the upper airway during sleep, leading to chronic intermittent hypoxia (CIH). 1 OSA is a common disease, present in 2% of women and 4% of men in the general U.S. population; however, the prevalence rises to 40% to 60% in obese individuals. 2,3 CIH of OSA has been associated with an increased risk of hypertension, type 2 diabetes, dyslipidemia, and atherosclerosis, independent of underlying obesity. 2,4-9 Moreover, studies in rodent models of intermittent hypoxia (IH) demonstrated that CIH can cause hypertension, 10 insulin resistance, 11 and dyslipidemia. 12,13 Thus, CIH of OSA has been implicated in causality of cardiovascular and metabolic disorders, independent of obesity.An emerging body of evidence indicates that OSA is associated with non-alcoholic steatohepatitis (NASH) and chronic liver injury in obese individuals. 14,15 Whether OSA can confer risk of NASH, independent of obesity, remains unclear. Two major mechanisms have been implicated in NASH: (1) hepatic steatosis, which is linked to insulin resistance; and (2) increased levels of oxidative stress with liver injury and subsequent inflammation. 16,17 We previously showed that CIH leads to progression of hepatic steatosis and insulin resistance in leptin-deficient obese mice. 12 However, the effects of CIH on hepatic lipids in the absence of obesity have not been examined. Whereas OSA and CIH induce oxidative stress and inflammation in multiple organs and tissues, 18-21 the impact

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“…The pathogenesis of NASH remains unclear. Nowadays, lipid metabolism abnormality, insulin resistance and oxidative stress and lipid peroxidation reaction [4][5][6][7][8] are thought to play an important role in the pathogenesis of NASH [9,10] . It was reported that the change of intestinal environment may play a role in NASH, which may be a cause of enterogenous endotoxemia [11,12] .…”

Section: Introductionmentioning

confidence: 99%

Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats

Sheng¹,

Wu²,

He³

et al. 2008

WJG

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AIM:To explore the change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis (NASH) in rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into control group and model group. Rats in the control group were given normal diet, and rats in the model group were given fat-rich diet. Eight rats in each group were killed at end of the 8th and 12th wk, respectively. The levels of endotoxin, D-xylose, TG, TC, ALT and AST, intestinal tissue SOD and MDA as well as intestinal mucus secretory IgA (sIgA) were measured. The pathology of liver was observed by HE staining. RESULTS: At end of the 8th wk, there was no marked difference in the levels of endotoxin, D-xylose and sIgA between the two groups. At end of the 12th wk, rats in the model group developed steatohepatitis and had a higher serum level of endotoxin (P = 0.01) and D-xylose (P = 0.00) and a lower serum level of sIgA (P = 0.007). CONCLUSION: Intestinal mucosa barrier malfunction may exist in NASH rats and may be an important promoter of NASH in rats.

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Insulin resistance in NASH

Cited by 45 publications

References 75 publications

Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease

Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease

Chronic intermittent hypoxia predisposes to liver injury†

Change of intestinal mucosa barrier function in the progress of non-alcoholic steatohepatitis in rats

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