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MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways.

Moore CE, Pickford J, Cagampang FR, Stead RL, Tian S, Zhao X, Tang X, Byrne CD, Proud CG - Sci Rep (2016)

Bottom Line: This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology.These data suggest MNK1 participates in mediating HFD-induced insulin resistance.Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.

ABSTRACT
The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease.

No MeSH data available.


Related in: MedlinePlus

Analysis of Mknk1 and Mknk2 mRNA expression.(a) Relative expression of Mknk1 (MNK1) and Mknk2 (MNK2) was determined by qPCR in liver and gonadal adipose tissue (n = 8). Data are mean ± SEM. (b) Immunoblot analysis of MNK1 protein levels in liver, adipose tissue, heart and skeletal muscle; representative of 4 independent experiments. (c) mRNA expression of PPARγ, C/EBPα, SREBP1c, GLUT4 and CD36 in differentiating 3T3-L1 adipocytes relative to day 0. Data are mean ± SEM, one-way ANOVA with Tukey’s post-test (n = 3). (d) mRNA expression for Mknk1 (MNK1) and Mknk2 (MNK2) in differentiating 3T3-L1 adipocytes relative to day 0 (n = 3). Data are mean ± SEM (one-way ANOVA with Tukey’s post-test) **P < 0.01, ***P < 0.001, ****P < 0.0001.
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f1: Analysis of Mknk1 and Mknk2 mRNA expression.(a) Relative expression of Mknk1 (MNK1) and Mknk2 (MNK2) was determined by qPCR in liver and gonadal adipose tissue (n = 8). Data are mean ± SEM. (b) Immunoblot analysis of MNK1 protein levels in liver, adipose tissue, heart and skeletal muscle; representative of 4 independent experiments. (c) mRNA expression of PPARγ, C/EBPα, SREBP1c, GLUT4 and CD36 in differentiating 3T3-L1 adipocytes relative to day 0. Data are mean ± SEM, one-way ANOVA with Tukey’s post-test (n = 3). (d) mRNA expression for Mknk1 (MNK1) and Mknk2 (MNK2) in differentiating 3T3-L1 adipocytes relative to day 0 (n = 3). Data are mean ± SEM (one-way ANOVA with Tukey’s post-test) **P < 0.01, ***P < 0.001, ****P < 0.0001.

Mentions: Earlier studies showed the MNK1 and MNK2 mRNAs are expressed in liver, skeletal muscle and heart5, tissues involved in insulin-regulated metabolism. The MNK1 and MNK2 mRNAs are also expressed in adipose tissue (Fig. 1a). In contrast, MNK2 is expressed only at low levels in some tissues, such as brain, where it makes only a small contribution to phosphorylation of eIF4E15. Immunoblot analysis revealed MNK1 protein expression in liver, skeletal and cardiac muscle and adipose tissue (Fig. 1b). As no suitable antibody is available for MNK216, we cannot study its levels.


MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways.

Moore CE, Pickford J, Cagampang FR, Stead RL, Tian S, Zhao X, Tang X, Byrne CD, Proud CG - Sci Rep (2016)

Analysis of Mknk1 and Mknk2 mRNA expression.(a) Relative expression of Mknk1 (MNK1) and Mknk2 (MNK2) was determined by qPCR in liver and gonadal adipose tissue (n = 8). Data are mean ± SEM. (b) Immunoblot analysis of MNK1 protein levels in liver, adipose tissue, heart and skeletal muscle; representative of 4 independent experiments. (c) mRNA expression of PPARγ, C/EBPα, SREBP1c, GLUT4 and CD36 in differentiating 3T3-L1 adipocytes relative to day 0. Data are mean ± SEM, one-way ANOVA with Tukey’s post-test (n = 3). (d) mRNA expression for Mknk1 (MNK1) and Mknk2 (MNK2) in differentiating 3T3-L1 adipocytes relative to day 0 (n = 3). Data are mean ± SEM (one-way ANOVA with Tukey’s post-test) **P < 0.01, ***P < 0.001, ****P < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4834573&req=5

f1: Analysis of Mknk1 and Mknk2 mRNA expression.(a) Relative expression of Mknk1 (MNK1) and Mknk2 (MNK2) was determined by qPCR in liver and gonadal adipose tissue (n = 8). Data are mean ± SEM. (b) Immunoblot analysis of MNK1 protein levels in liver, adipose tissue, heart and skeletal muscle; representative of 4 independent experiments. (c) mRNA expression of PPARγ, C/EBPα, SREBP1c, GLUT4 and CD36 in differentiating 3T3-L1 adipocytes relative to day 0. Data are mean ± SEM, one-way ANOVA with Tukey’s post-test (n = 3). (d) mRNA expression for Mknk1 (MNK1) and Mknk2 (MNK2) in differentiating 3T3-L1 adipocytes relative to day 0 (n = 3). Data are mean ± SEM (one-way ANOVA with Tukey’s post-test) **P < 0.01, ***P < 0.001, ****P < 0.0001.
Mentions: Earlier studies showed the MNK1 and MNK2 mRNAs are expressed in liver, skeletal muscle and heart5, tissues involved in insulin-regulated metabolism. The MNK1 and MNK2 mRNAs are also expressed in adipose tissue (Fig. 1a). In contrast, MNK2 is expressed only at low levels in some tissues, such as brain, where it makes only a small contribution to phosphorylation of eIF4E15. Immunoblot analysis revealed MNK1 protein expression in liver, skeletal and cardiac muscle and adipose tissue (Fig. 1b). As no suitable antibody is available for MNK216, we cannot study its levels.

Bottom Line: This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology.These data suggest MNK1 participates in mediating HFD-induced insulin resistance.Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease.

View Article: PubMed Central - PubMed

Affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.

ABSTRACT
The MAP kinase-interacting kinases (MNK1 and MNK2) are non-essential enzymes which are activated by MAP kinases. They are implicated in controlling protein synthesis. Here we show that mice in which the expression of either MNK1 or MNK2 has been knocked out (KO) are protected against adverse effects of high-fat feeding, and in distinct ways. High-fat diet (HFD)-fed MNK2-KO show less weight gain than wild-type animals, and improved glucose tolerance, better insulin sensitivity and markedly diminished adipose tissue inflammation. This suggests MNK2 plays a role in adipogenesis and/or lipogenesis and in macrophage biology. MNK1-KO/HFD mice show better glucose tolerance and insulin sensitivity, but gain weight and show similar adipose inflammation to WT animals. These data suggest MNK1 participates in mediating HFD-induced insulin resistance. Our findings reveal distinct roles for the MNKs in a novel area of disease biology, metabolic dysfunction, and suggests they are potential new targets for managing metabolic disease.

No MeSH data available.


Related in: MedlinePlus