Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients

Haynes, Vanessa; Connor, Timothy; Tchernof, André; Vidal, Hubert; Dubois, Séverine

doi:10.1016/j.ymgme.2012.10.012

Cited by 16 publications

(12 citation statements)

References 31 publications

(34 reference statements)

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“…However, it is not excluded that insulin stimulated glucose influx into adipocytes could be responsible for the inhibition of gene expression encoding MT1 and MT2 in WAT. Although our experimental data cannot be directly extrapolated to humans, the previously reported increase in MT2a gene expression in the adipose tissue from type 2 diabetic patients [ 16 ] and obese subject [ 7 , 11 ] might be at least in part associated with insulin insensitivity.…”

Section: Discussionmentioning

confidence: 94%

“…Furthermore, these MTs may play a role in the prevention of high-fat diet-induced obesity [ 37 ]. Moreover, human studies documented enhanced expression of MT2a encoding gene in adipose tissue from an obese subject [ 7 , 11 ] and patients with type 2 diabetes [ 16 ]. This implies that the upregulation of MT gene expression in human adipose tissue may exert a detrimental effect promoting obesity or be a consequence of obesity.…”

Section: Introductionmentioning

confidence: 99%

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Metallothioneins 1 and 2, but not 3, are regulated by nutritional status in rat white adipose tissue

et al. 2016

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BackgroundCumulating evidence underlines the role of adipose tissue metallothionein (MT) in the development of obesity and type 2 diabetes. Fasting/refeeding was shown to affect MT gene expression in the rodent liver. The influence of nutritional status on MT gene expression in white adipose tissue (WAT) is inconclusive. The aim of this study was to verify if fasting and fasting/refeeding may influence expression of MT genes in WAT of rats.ResultsFasting resulted in a significant increase in MT1 and MT2 gene expressions in retroperitoneal, epididymal, and inguinal WAT of rats, and this effect was reversed by refeeding. Altered expressions of MT1 and MT2 genes in all main fat depots were reflected by changes in serum MT1 and MT2 levels. MT1 and MT2 messenger RNA (mRNA) levels in WAT correlated inversely with serum insulin concentration. Changes in MT1 and MT2 mRNA levels were apparently not related to total zinc concentrations and MTF1 and Zn transporter mRNA levels in WAT. Fasting or fasting/refeeding exerted no effect on the expression of MT3 gene in WAT. Addition of insulin to isolated adipocytes resulted in a significant decrease in MT1 and MT2 gene expressions. In contrast, forskolin or dibutyryl-cAMP (dB-cAMP) enhanced the expressions of MT1 and MT2 genes in isolated adipocytes. Insulin partially reversed the effect of dB-cAMP on MT1 and MT2 gene expressions.ConclusionsThis study showed that the expressions of MT1 and MT2 genes in WAT are regulated by nutritional status, and the regulation may be independent of total zinc concentration.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0533-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Metallothioneins 1 and 2, but not 3, are regulated by nutritional status in rat white adipose tissue

et al. 2016

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“…showed that MT treatment inhibited insulin-stimulated glucose uptake by 3T3-L1 adipocytes. [39] Fu et al . reported that MT1G suppressed thyroid cancer cells by inhibiting the PI3K/Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the insulin signaling pathway

et al. 2017

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Knockout of metallothionein (MT) genes contributes to a heavier body weight in early life and the potential to become obese through the intake of a high fat diet (HFD) in mice. It has thus been suggested that MT genes regulate the formation of adipose tissue, which would become the base for later HFD-induced obesity. We evaluated the fat pads of mice during the lactation stage. The fat mass and adipocyte size of MT1 and MT2 knockout mice were greater than those of wild type mice. Next, we assayed the ability of small interfering RNA (siRNA) to silence MT genes in the 3T3-L1 cell line. The expressions of MT1 and MT2 genes were transiently upregulated during adipocyte differentiation, and the siRNA pretreatment led to the suppression of the expression of both MT mRNAs and proteins. The MT siRNA promoted lipid accumulation in adipocytes and caused proliferation of post-confluent preadipocytes; these effects were suppressed by an inhibitor of phosphatidylinositol 3-kinase (LY294002). In addition, MT siRNA promoted insulin-stimulated phosphorylation of Akt, a downstream kinase of the insulin signaling pathway. Enhanced lipid accumulation in 3T3-L1 cells resulting from MT-gene silencing was inhibited by pretreatment with an antioxidant, N-acetylcysteine, used as a substitute for antioxidant protein MTs. These results suggest that interference in MT expression enhanced the activation of the insulin signaling pathway, resulting in higher lipid accumulation in 3T3-L1 adipocytes.

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“…Li et al [ 58 ] have demonstrated that zinc deficiency suppresses Nrf2 activity in diabetes-induced renal oxidative damage in mice. The intracellular concentration of zinc is partly regulated through MTs and closely linking the redox status of the cell to cellular availability of zinc ions [ 61 ].…”

Section: Introductionmentioning

confidence: 99%

Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism

et al. 2017

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A number of studies have reported that zinc plays a substantial role in the development of metabolic syndrome, taking part in the regulation of cytokine expression, suppressing inflammation, and is also required to activate antioxidant enzymes that scavenge reactive oxygen species, reducing oxidative stress. Zinc also plays a role in the correct functioning of lipid and glucose metabolism, regulating and forming the expression of insulin. In numerous studies, zinc supplementation has been found to improve blood pressure, glucose, and LDL cholesterol serum level. Deeper knowledge of zinc’s properties may help in treating metabolic syndrome, thus protecting against stroke and angina pectoris, and ultimately against death.

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Metallothionein 2a gene expression is increased in subcutaneous adipose tissue of type 2 diabetic patients

Cited by 16 publications

References 31 publications

Metallothioneins 1 and 2, but not 3, are regulated by nutritional status in rat white adipose tissue

Metallothioneins 1 and 2, but not 3, are regulated by nutritional status in rat white adipose tissue

Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the insulin signaling pathway

Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism

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