Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice

Liu, Kun; Ruan, Xiong Z.; Powis, Stephen H.; Chen, Yaxi; Moorhead, John F.; Varghese, Zac

doi:10.1002/hep.22423

Cited by 220 publications

(172 citation statements)

References 27 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…Results similar to ours have been found in liver cells, where TNF-␣ and IL-1 caused a marked decrease in retinoid X receptor ␣, PPAR␣, PPAR␥, LXR␣ and SREBP-1c (97). In the liver of apoE knockout mice and in HepG2 cells, inflammatory stress inhibited PPAR␣ and LXR␣ but increased cholesterol accumulation and SREBP-2 (98). Similarly, hepatic mRNA levels of LXR and retinoid X receptor together with their target genes were rapidly decreased by LPS and proinflammatory cytokines in rodents during the acute phase response (99).…”

Section: Discussionsupporting

confidence: 89%

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

Marcil

Seidman

Sinnett

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 89%

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

Marcil

Seidman

Sinnett

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Several lines of evidence demonstrate that exposure to a HFD and diet-induced obesity lead to overproduction of proinflammatory cytokines such as TNF-α and excessive release of FFA, which are both believed to be critical in the progression of NAFLD [35,36] , as well as for the development of insulin resistance [36] . Indeed, our data showed that rats fed a HFD for 16 weeks exhibited a significant increase in serum TNFα.…”

Section: Discussionmentioning

confidence: 99%

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

et al. 2009

View full text Add to dashboard Cite

Aim: Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated. Methods: Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined. Results: Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor α. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 µmol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose. Conclusion: Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.

show abstract

“…S.c. casein injection is an established method for the induction of chronic systemic inflammation in mouse models. This has been used in many studies of atherosclerosis and liver steatosis (Miura et al 1985, Wal 2002, Ma et al 2008. In comparison with other sole cytokine or lipopolysaccharide (LPS)-induced mouse models, casein injection induces a lower degree inflammatory stress characterized by increased multiple cytokines (IL1b, TNFa, and IL6) and SAA (like CRP in human) levels in serum, which is more likely to mimic chronic systemic inflammatory state observed in patients with inflammatory stress (Zhang et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet

Wu¹,

Wu²,

Wu³

et al. 2013

Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Inflammatory stress is closely related to metabolic disease and insulin resistance. The precise cellular mechanism linking obesity and diabetes is largely unknown, but about 14-20% of obese individuals develop diabetes. In this study, we investigated whether chronic inflammation exacerbated glucose metabolism disorder by impairing b cell function in high-fat diet (HFD)-fed C57BL/6J mice. We used s.c. casein injection to induce chronic inflammation in HFD-fed C57BL/6J mice; 14 weeks on a HFD resulted in weight gain, hyperlipidemia, and low insulin sensitivity in these mice which nevertheless had normal blood glucose and serum inflammatory cytokines levels. Casein injection in the background of HFD elevated serum tumor necrosis factor a (TNFa) and serum amyloid A levels and increased TNFa and MCP1 expression in the adipose tissue, liver, and muscle of HFD-fed mice. Chronic inflammation induced by casein injection further decreased insulin sensitivity and insulin signaling, resulting in insulin deficiency and hyperglycemia in these mice. Islet mass and insulin content were markedly increased in HFD mice. However, in contrast with HFD-fed alone, chronic inflammation in HFD-fed mice decreased both islet mass and insulin content, reduced the genetic expression of insulin synthesis and secretion, and increased b cell apoptosis. We conclude that chronic inflammation exacerbated glucose metabolism disorders by impairing b cell function in HFD-fed C57BL/6J mice, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to hyperglycemia. Key Words" glucose metabolism " inflammatory diseases " insulin " apoptosis " pancreas

show abstract

Inflammatory stress exacerbates lipid accumulation in hepatic cells and fatty livers of apolipoprotein E knockout mice

Cited by 220 publications

References 27 publications

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

Modification in Oxidative Stress, Inflammation, and Lipoprotein Assembly in Response to Hepatocyte Nuclear Factor 4α Knockdown in Intestinal Epithelial Cells

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice fed with high-fat diet

Contact Info

Product

Resources

About