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Downregulation of zinc-{alpha}2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-alpha in adipocytes.

Mracek T, Gao D, Tzanavari T, Bao Y, Xiao X, Stocker C, Trayhurn P, Bing C - J. Endocrinol. (2009)

Bottom Line: The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes.In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats.Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment.

View Article: PubMed Central - PubMed

Affiliation: Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.

ABSTRACT
Zinc-alpha2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfalpha mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFalpha.

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Related in: MedlinePlus

ZAG protein expression in adipose tissue of ob/ob and lean mice. Protein was extracted from subcutaneous and epididymal fat of lean (ob/+) and ob/ob mice, and western blotting was used for protein expression of ZAG, COX IV, SDH 70 and α-tubulin. Representative western blot and quantification of protein expression normalised to α-tubulin in subcutaneous (A and B) and epididymal (C and D) fat. Data are means±s.e.m. for groups of 6. *P<0·05, ***P<0·001 compared with lean controls.
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fig2: ZAG protein expression in adipose tissue of ob/ob and lean mice. Protein was extracted from subcutaneous and epididymal fat of lean (ob/+) and ob/ob mice, and western blotting was used for protein expression of ZAG, COX IV, SDH 70 and α-tubulin. Representative western blot and quantification of protein expression normalised to α-tubulin in subcutaneous (A and B) and epididymal (C and D) fat. Data are means±s.e.m. for groups of 6. *P<0·05, ***P<0·001 compared with lean controls.

Mentions: ZAG protein expression in adipose tissue of mice was assessed next by western blotting. Consistent with the data on Zag gene expression, there were decreases in ZAG protein levels in subcutaneous (−29%, P<0·05) and epididymal (−34%, P<0·001) fat of ob/ob mice relative to their lean controls (Fig. 2A and B). We also determined the levels of COX IV and SDH 70 protein as a measure of mitochondrial oxidative phosphorylation capacity in adipocytes (Choo et al. 2006). Protein expression of COX IV and SDH 70 in ob/ob mice was unchanged (both P>0·05; Fig. 2A and B) in the fat depots.


Downregulation of zinc-{alpha}2-glycoprotein in adipose tissue and liver of obese ob/ob mice and by tumour necrosis factor-alpha in adipocytes.

Mracek T, Gao D, Tzanavari T, Bao Y, Xiao X, Stocker C, Trayhurn P, Bing C - J. Endocrinol. (2009)

ZAG protein expression in adipose tissue of ob/ob and lean mice. Protein was extracted from subcutaneous and epididymal fat of lean (ob/+) and ob/ob mice, and western blotting was used for protein expression of ZAG, COX IV, SDH 70 and α-tubulin. Representative western blot and quantification of protein expression normalised to α-tubulin in subcutaneous (A and B) and epididymal (C and D) fat. Data are means±s.e.m. for groups of 6. *P<0·05, ***P<0·001 compared with lean controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2807359&req=5

fig2: ZAG protein expression in adipose tissue of ob/ob and lean mice. Protein was extracted from subcutaneous and epididymal fat of lean (ob/+) and ob/ob mice, and western blotting was used for protein expression of ZAG, COX IV, SDH 70 and α-tubulin. Representative western blot and quantification of protein expression normalised to α-tubulin in subcutaneous (A and B) and epididymal (C and D) fat. Data are means±s.e.m. for groups of 6. *P<0·05, ***P<0·001 compared with lean controls.
Mentions: ZAG protein expression in adipose tissue of mice was assessed next by western blotting. Consistent with the data on Zag gene expression, there were decreases in ZAG protein levels in subcutaneous (−29%, P<0·05) and epididymal (−34%, P<0·001) fat of ob/ob mice relative to their lean controls (Fig. 2A and B). We also determined the levels of COX IV and SDH 70 protein as a measure of mitochondrial oxidative phosphorylation capacity in adipocytes (Choo et al. 2006). Protein expression of COX IV and SDH 70 in ob/ob mice was unchanged (both P>0·05; Fig. 2A and B) in the fat depots.

Bottom Line: The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes.In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats.Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment.

View Article: PubMed Central - PubMed

Affiliation: Obesity Biology Research Unit, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.

ABSTRACT
Zinc-alpha2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfalpha mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFalpha.

Show MeSH
Related in: MedlinePlus