Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice

Gregoire, Francine M.; Zhang, Qin; Smith, Steven J.; Tong, Carmen H.; Ross, David A.; Lopez, Henry; West, David B.

doi:10.1152/ajpendo.00072.2001

Cited by 103 publications

(80 citation statements)

References 44 publications

(47 reference statements)

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“…Furthermore, previous studies have reported that steatotic livers produce increased levels of complement proteins de novo (46), which may also contribute to the apparent increase in C3d immunostaining. Nevertheless, CR2-Crry treatment resulted in a significant reduction in immunostaining for C3d in livers from both lean and steatotic mice after I/R and posttransplantation.…”

Section: Discussionmentioning

confidence: 94%

A Role for Complement in the Enhanced Susceptibility of Steatotic Livers to Ischemia and Reperfusion Injury

Atkinson²,

Evans

et al. 2009

The Journal of Immunology

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Hepatic steatosis typically renders the donor organ unusable, as donor organs with >30% steatosis are more likely to develop graft failure. The mechanisms leading to failure are not well defined, but steatosis enhances hepatic susceptibility to ischemia reperfusion injury (IRI). We investigated the role of complement in hepatic IRI in lean and steatotic (diet-induced) mice. Steatotic mice were significantly more susceptible to total warm hepatic IRI than lean mice as determined by serum alanine aminotransferase, histopathologically assessed damage, and 24-h survival. C3 deficiency protected both lean and steatotic mice from IRI, as determined by all measured outcomes. Furthermore, treatment of wild-type mice with the complement inhibitor CR2-Crry provided protection equivalent to that seen in C3-deficient mice. Importantly, although steatotic livers were much more susceptible to IRI than lean livers, by most measures there was no statistical difference between the level of IRI to steatotic or lean livers when complement was inhibited. To investigate the clinical relevance of these findings in the context of transplantation, we treated recipients of lean or steatotic liver grafts with saline or CR2-Crry. There was a marked reduction in graft inflammation and injury and significantly improved 7-day survival in CR2-Crry-treated recipients of either lean or steatotic grafts. These data indicate that complement plays a key role in the enhanced susceptibility of steatotic livers to IRI and suggest that complement inhibition represents a potential strategy to reduce the donor shortage by allowing the more routine use of marginal steatotic donor livers.

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Section: Discussionmentioning

confidence: 94%

A Role for Complement in the Enhanced Susceptibility of Steatotic Livers to Ischemia and Reperfusion Injury

Atkinson²,

Evans

et al. 2009

The Journal of Immunology

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“…Although once thought to be expressed exclusively in adipocytes, adipsin mRNA is found in the gastrointestinal tract, spleen, and liver (16,29). Factor D is unique among complement components in that it does not require proteolytic processing for activation; and it exhibits exceptional specificity for its substrate C3bB (43).…”

Section: Discussionmentioning

confidence: 99%

“…This, of course, is not surprising, given the plethora of genes that are transcriptionally regulated by cellular uptake of cholesterol and fatty acids. For example, in a recent study of mouse liver gene expression, SREBP-1, apolipoprotein A-IV, and adipsin (factor D) were all upregulated by a Western diet (16). Most of these cholesterolgenic genes, however, are downregulated with high-fat feeding to varying degrees in both control and LDLR-deficient mice (and hence cluster in the lower portion of Fig.…”

Section: Liver Gene Expression In Atherosclerosis-prone Micementioning

confidence: 96%

Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway

Recinos

Carr

Bartos

et al. 2004

Physiological Genomics

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“…6,7 C57BL/6J mice also develop fatty liver in response to an HF diet. [8][9][10] However, they are resistant to sucrose/fructose-induced fatty liver because they possess adenine Ϫ468 bp from the putative 5Ј end of the sterol regulatory element-binding protein (SREBP)-1c gene. 11 Mice with guanine at this site show increased liver SREBP-1c messenger RNA (mRNA) in response to a high-fructose diet, whereas mice with adenine do not.…”

mentioning

confidence: 99%

Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice

Yamazaki

Nakamori²,

Sasaki³

et al. 2007

Hepatology

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Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). We analyzed the effects of dietary fish oil on fatty liver induced by sucrose, safflower oil, and butter in ddY mice. In experiment I, mice were fed a high-starch diet [70 energy% (en%) starch] plus 20% (wt/wt) sucrose in the drinking water or fed a high-safflower oil diet (60 en%) for 11 weeks. As a control, mice were fed a high-starch diet with drinking water. Fish oil (10 en%) was either supplemented or not. Mice supplemented with sucrose or fed safflower oil showed a 1.7-fold or 2.2-fold increased liver triglyceride content, respectively, compared with that of control mice. Fish oil completely prevented sucrose-induced fatty liver, whereas it exacerbated safflower oil-induced fatty liver. Sucrose increased SREBP-1c and target gene messenger RNAs (mRNAs), and fish oil completely inhibited these increases. In experiment II, mice were fed a high-safflower oil or a high-butter diet, with or without fish oil supplementation. Fish oil exacerbated safflower oilinduced fatty liver but did not affect butter-induced fatty liver. Fish oil increased expression of peroxisome proliferator-activated receptor gamma (PPAR␥) and target CD36 mRNA in safflower oil-fed mice. These increases were not observed in sucrose-supplemented or butter-fed mice. Conclusion: The effects of dietary fish oil on fatty liver differ according to the cause of fatty liver; fish oil prevents sucrose-induced fatty liver but exacerbates safflower oil-induced fatty liver. The exacerbation of fatty liver may be due, at least in part, to increased expression of liver PPAR␥.

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Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice

Cited by 103 publications

References 44 publications

A Role for Complement in the Enhanced Susceptibility of Steatotic Livers to Ischemia and Reperfusion Injury

A Role for Complement in the Enhanced Susceptibility of Steatotic Livers to Ischemia and Reperfusion Injury

Liver gene expression associated with diet and lesion development in atherosclerosis-prone mice: induction of components of alternative complement pathway

Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice

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