The adipokine zinc‐α2‐glycoprotein (ZAG) is downregulated with fat mass expansion in obesity

Mráček, Tomáš; Ding, Qi; Tzanavari, Theodora; Kos, Katarina; Pinkney, Jonathan; Wilding, John; Trayhurn, Paul; Chen, Bing

doi:10.1111/j.1365-2265.2009.03658.x

Cited by 98 publications

(130 citation statements)

References 31 publications

(62 reference statements)

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“…14 Also importantly, the level of ZAG release by human adipocytes has recently been demonstrated to be comparable with that of adiponectin (which is one of the most abundant proteins in adipose tissue). 41 Collectively, these findings indicate that ZAG is a major adipokine produced abundantly by human adipocytes. From this it seems probable that adipocyte-derived ZAG may have an autocrine/paracrine action locally, and will also contribute to circulating levels of the protein, in the control of adipose tissue mass and function ( Figure 1).…”

Section: Identification Of Zag As a New Adipokinementioning

confidence: 94%

“…41,56 An inverse relationship has also been found between ZAG mRNA and plasma C-reactive protein or monocyte chemotactic protein-1, both of which are important in inflammatory responses and predict an increased risk of type 2 diabetes. 41 Moreover, ZAG mRNA levels in subcutaneous depot were downregulated in patients with the metabolic syndrome compared with those without. 56 Thus, decreased ZAG expression with increased insulin resistance may indicate a protective role of ZAG in maintaining appropriate fat mass and insulin sensitivity.…”

Section: Zag Expression and Body Fat Massmentioning

confidence: 95%

“…[54][55][56] Interestingly, a negative correlation between adipose-derived ZAG and body mass index or total body fat mass in human subjects has been demonstrated by studies from our group and from others. 41,55,56 Reduced ZAG expression in adipose tissue in the obese state may therefore be linked to impaired adipose tissue metabolism in obesity.…”

Section: Zag Expression and Body Fat Massmentioning

confidence: 99%

“…13 Further studies using paired visceral and subcutaneous samples do not show depot differences at either the mRNA or protein levels. 41 ZAG gene expression and ZAG protein have both been detected in isolated human fat cells, SGBS ZAG and adiposity C Bing et al (Simpson-Golabi-Behmel syndrome) human adipocyte cell strain 14 and human primary adipocytes (ZenBio). 42 Importantly, ZAG, which contains a secretory signal sequence, 18 is secreted into the culture medium by differentiated adipocytes.…”

Section: Identification Of Zag As a New Adipokinementioning

confidence: 99%

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Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

et al. 2010

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The importance of white adipose tissue in the control of energy balance is now firmly recognized. In addition to fuel storage, adipocytes secrete an array of proteins factors (adipokines), which regulate multiple physiological and metabolic processes as well as influence body fat accumulation. Zinc-a2-glycoprotein (ZAG), a lipid mobilizing factor initially characterized as a tumor product associated with cachexia, has recently been identified as a novel adipokine. Although the exact role of ZAG in adipose tissue remains to be clarified, there is evidence that ZAG expression appears to be inversely related to adiposity, being upregulated in cachexia whereas reduced in obesity. Investigations on the regulation of ZAG give insights into its potential function in adipose tissue with a link to lipid mobilization and an anti-inflammatory action. Recent work shows that ZAG stimulates adiponectin secretion by human adipocytes. Data from genetic studies suggest that ZAG may be a candidate gene for body weight regulation; this is supported by the demonstration that ZAG-knockout mice are susceptible to weight gain, whereas transgenic mice overexpressing ZAG exhibit weight loss. The present review summarizes these new perspectives of ZAG and the potential mechanisms by which it might modulate adipose tissue mass and function.

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Section: Identification Of Zag As a New Adipokinementioning

confidence: 94%

Section: Zag Expression and Body Fat Massmentioning

confidence: 95%

Section: Zag Expression and Body Fat Massmentioning

confidence: 99%

Section: Identification Of Zag As a New Adipokinementioning

confidence: 99%

See 2 more Smart Citations

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

et al. 2010

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“…In contrast ZAG mRNA levels in WAT have been shown to be down regulated in obesity and correlated negatively with fat mass, BMI, plasma insulin and leptin (5). Treatment of ob/ob mice with ZAG decreased body weight and fat mass and improved the parameters of insulin resistance including decreasing plasma levels of glucose, insulin and non-esterified fatty acids (NEFA), improving insulin sensitivity, and increasing muscle mass (6).…”

mentioning

confidence: 99%

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Russell

Tisdale

2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Objectives:The goal of the current study is to determine whether the -adrenoreceptor (-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-2-glycoprotein (ZAG). Material and Methods:This has been investigated in CHO-K1 cells transfected with the human 1-, 2-, 3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranonol.Results: ZAG bound to the 3-AR with higher affinity (Kd 46+1nM) than the 2-AR (Kd 71+3nM) while there was no binding to the 1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various -AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of 3-AR in gastrocnemius muscle, and in white and brown adipose tissue, but had no effect on expression of 1-and 2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, was completely attenuated by the non-specific -AR antagonist propranolol. Conclusion:The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a -3AR, or possibly a 2-AR.

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Contiguous mutation syndrome in the era of high‐throughput sequencing

Langouët

Siquier-Pernet

Sanquer

et al. 2015

Molec Gen & Gen Med

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We investigated two siblings, born to consanguineous parents, with neurological features reminiscent of adaptor protein complex 4 (AP4) deficiency, an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity, severe intellectual disability speech delay, microcephaly, and growth retardation. Yet, both children also presented with early onset obesity. Whole-exome sequencing identified two homozygous substitutions in two genes 170 kb apart on 7q22.1: a c.1137+1G>T splice mutation in AP4M1 previously described in a familial case of AP4-deficiency syndrome and the AZGP1 c.595A>T missense variant. Haplotyping analysis indicated a founder effect of the AP4M1 mutation, whereas the AZGP1 mutation arose more recently in our family. AZGP1 encodes an adipokine that stimulate lipolysis in adipocytes and regulates body weight in mice. We propose that the siblings' phenotype results from the combined effects of mutations in both AP4M1 and AZGP1 that account for the neurological signs and the morbid obesity of early onset, respectively. Contiguous gene syndromes are the consequence of loss of two or more adjacent genes sensible to gene dosage and the phenotype reflects a combination of endophenotypes. We propose to broaden this concept to phenotypes resulting from independent mutations in two genetically linked genes causing a contiguous mutation syndrome.

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The adipokine zinc‐α2‐glycoprotein (ZAG) is downregulated with fat mass expansion in obesity

Cited by 98 publications

References 31 publications

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

Zinc-α2-glycoprotein: an adipokine modulator of body fat mass?

Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Contiguous mutation syndrome in the era of high‐throughput sequencing

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