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

Szrok, Sylwia; Stelmańska, Ewa; Turyn, Jacek; Bielicka–Giełdoń, Aleksandra; Śledziński, Tomasz; Świerczyński, Julian

doi:10.1186/s12263-016-0533-3

Cited by 12 publications

(11 citation statements)

References 51 publications

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“…Mt3 mRNA in the liver was not considered expressed since the ΔCt values were much higher compared with Mt1 and Mt2 ( Appendix A , Table A2 ). This finding coincides with several previous reports of Mt3 gene and protein expression being absent in mouse and rat liver [ 14 , 15 , 34 , 35 ]. The qPCR Ct values for β- actin that were used for target gene normalization are reported in Appendix A , Table A5 .…”

Section: Resultssupporting

confidence: 93%

“…Moreover, MT-1/2-deficient mice are more susceptible to neuronal damage associated with kainic acid (KA)-induced seizures [ 12 ]. In mammals, MT-1 and MT-2 (MT-1/2) expression is ubiquitous, whereas MT-3 is mainly localized to the brain but is expressed to a lesser degree in other organs [ 13 , 14 , 15 ]. MT-4 expression is largely confined to stratified epithelial cells associated with skin, esophagus, and the stomach [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

Mehus

Picklo

2017

Nutrients

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Metallothioneins (MTs) perform important regulatory and cytoprotective functions in tissues including the brain. While it is known that energy restriction (ER) and dietary n-3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal brain growth and development, little data exist regarding the impact of undernutrition upon MT expression in growing animals. We tested the hypothesis that ER with and without dietary n-3 PUFA deficiency reduces MT expression in juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL) intake of control rats provided diets consisting of either soybean oil (SO) that is α-linolenic acid (ALA; 18:3n-3) sufficient or corn oil (CO; ALA-deficient). Fatty acids (FA) and metal concentrations of liver and brain regions were analyzed. Tissue expression of MTs (Mt1-3) and modulators of MT expression including glucocorticoid receptors (Nr3c1 and Nr3c2) and several mediators of thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb) were measured. Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral cortex (23%). In liver, a reduction in dietary n-3 PUFA reduced Mt1, Mt2, Nr3c1, Mct8, and Thrb. ER elevated Nr3c1, Dio1, and Thrb and reduced Thra in the liver. Given MT’s role in cellular protection, further studies are needed to evaluate whether ER or n-3 PUFA deficiency may leave the juvenile brain and/or liver more susceptible to endogenous or environmental stressors.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

Mehus

Picklo

2017

Nutrients

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“…In fact, MTs seem to prevent high‐fat diet‐induced obesity and MT gene expression in mice liver is influenced by fasting/refeeding, being increased by fasting . Similar results were also found in rat adipose tissue …”

Section: Discussionsupporting

confidence: 73%

Combined effects of DDE and hyperlipidic diet on metallothionein expression and synthesis in rat tissues

Migliaccio

Lionetti

Putti

et al. 2018

Environmental Toxicology

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Metallothionein is well known for its detoxificant and anti-oxidant properties and has been shown to be effective to prevent hydroxyl radical-generated DNA degradation. The purpose of this investigation was to analyze the combined effect of two factors promoting cellular oxidative-stress, that is, the administration of the pesticide dichloro-diphenyl-dichloroethylene (DDE) and a high fat diet, on metallothionein expression and synthesis in rat liver and kidney.DDE is the main metabolite of dichloro-diphenyl-trichloroethane (DDT), and is commonly found in the food chain and in all tissues of living organisms, carried by the fats. Male Wistar rats were fed with a standard (N) or a high fat (HF) diet and exposed to DDE (10 mg/kg body mass, N + DDE and HF + DDE groups) or vehicle (corn oil, N, and HF groups) via gavage every day for 28 days. Tissues histology was determined by light microscopy analysis; differences in metallothionein gene expression and synthesis by real-time PCR and western blot, respectively.Finally, protein cellular localization was established by immunocytochemistry. The results showed a different involvement of metallothionein in defending tissues from HF-and DDEinduced oxidative stress, suggesting that hepatic and renal cells use different strategies against pro-oxidant species. In both cell types a marked increase in the metallothionein content was observed in the nucleus, with a concomitant drop of the cytoplasmatic protein, either under HFand DDE-stress conditions; however, no synergistic or additive effects were observed between the action of fats and pesticide. These findings reinforce the role of metallothionein in protecting DNA from oxidative damage. K E Y W O R D SDDE and oxidative stress, gene expression, high fat diet, metallothionein, protein synthesis and localization

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“…[ 31 , 32 ] MTs were induced by treatment with dexamethasone and activators of the cAMP/PKA pathway, i.e., forskolin and bromo-cAMP, in rat adipocytes. [ 15 , 33 ] MT expression in rat liver was also regulated by cAMP and glucocorticoids. [ 34 ] Similar to these results, we showed that dexamethasone mainly upregulated MT expression ( Fig 5 ).…”

Section: Discussionmentioning

confidence: 99%

“…[ 13 ] Obesity beginning in childhood is characterized by hyperplasia and hypertrophy, and adult-onset obesity is characterized by hypertrophy. MT1, MT2, and MT3 express in adipose tissue [ 14 ], and the expression of MT1 and MT2 in rodents is affected by nutritional status [ 15 ]. We previously reported that female MT1 and MT2 knockout (MTKO) mice developed high-fat-diet (HFD)-induced obesity, but that a standard diet did not induce obesity in the mice.…”

Section: Introductionmentioning

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

Cited by 12 publications

References 51 publications

Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n-3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats

Combined effects of DDE and hyperlipidic diet on metallothionein expression and synthesis in rat tissues

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

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