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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 macrophage markers in adipose tissue from WT and MNK-KO mice.(a,b) Total RNA was isolated from gonadal adipose tissue from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice. The relative expression of mRNA for general macrophage markers (CD68 and F4/80) was measured by means of qPCR. Data are mean ± SEM relative to WT chow (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01. (c–e) The relative expression of mRNA for M1 polarized macrophages (TNFα, CD11c and MHCII) was measured by means of qPCR, (n = 3–4). Data are mean ± SEM relative to WT chow (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001.
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f6: Analysis of macrophage markers in adipose tissue from WT and MNK-KO mice.(a,b) Total RNA was isolated from gonadal adipose tissue from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice. The relative expression of mRNA for general macrophage markers (CD68 and F4/80) was measured by means of qPCR. Data are mean ± SEM relative to WT chow (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01. (c–e) The relative expression of mRNA for M1 polarized macrophages (TNFα, CD11c and MHCII) was measured by means of qPCR, (n = 3–4). Data are mean ± SEM relative to WT chow (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: A further major consequence of consuming a HFD is inflammation in adipose tissue, which becomes infiltrated with pro-inflammatory M1 macrophages1. WT/HFD and MNK1-KO/HFD mice both showed the expected increases, compared to chow-fed animals, in adipose tissue mRNA levels for macrophage markers such as CD68 and F4/80 (Fig. 6a,b). In marked contrast, MNK2-KO/HFD mice showed sharply blunted inflammation, with less or no increase in CD68, F4/80 and MHCII (Fig. 6a,b,e).


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 macrophage markers in adipose tissue from WT and MNK-KO mice.(a,b) Total RNA was isolated from gonadal adipose tissue from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice. The relative expression of mRNA for general macrophage markers (CD68 and F4/80) was measured by means of qPCR. Data are mean ± SEM relative to WT chow (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01. (c–e) The relative expression of mRNA for M1 polarized macrophages (TNFα, CD11c and MHCII) was measured by means of qPCR, (n = 3–4). Data are mean ± SEM relative to WT chow (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Analysis of macrophage markers in adipose tissue from WT and MNK-KO mice.(a,b) Total RNA was isolated from gonadal adipose tissue from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice. The relative expression of mRNA for general macrophage markers (CD68 and F4/80) was measured by means of qPCR. Data are mean ± SEM relative to WT chow (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01. (c–e) The relative expression of mRNA for M1 polarized macrophages (TNFα, CD11c and MHCII) was measured by means of qPCR, (n = 3–4). Data are mean ± SEM relative to WT chow (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: A further major consequence of consuming a HFD is inflammation in adipose tissue, which becomes infiltrated with pro-inflammatory M1 macrophages1. WT/HFD and MNK1-KO/HFD mice both showed the expected increases, compared to chow-fed animals, in adipose tissue mRNA levels for macrophage markers such as CD68 and F4/80 (Fig. 6a,b). In marked contrast, MNK2-KO/HFD mice showed sharply blunted inflammation, with less or no increase in CD68, F4/80 and MHCII (Fig. 6a,b,e).

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