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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 marker genes in BMDMs from WT and MNK2-KO mice.(a,b) Plasma levels of IL-5 and IL-10 from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice were measured by ELISA (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05. (c–f) BMDMs isolated from WT or MNK2-KO mice were cultured for 24 h in the presence or absence of IL-4 to polarize the BMDMs towards an M2 phenotype. The mRNA expression levels of the M2 markers IL10, CD206, PPARγ, STAT6 and IRF4 were measured by qPCR (n = 6). Data are mean ± SEM relative to WT Control (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
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f7: Analysis of marker genes in BMDMs from WT and MNK2-KO mice.(a,b) Plasma levels of IL-5 and IL-10 from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice were measured by ELISA (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05. (c–f) BMDMs isolated from WT or MNK2-KO mice were cultured for 24 h in the presence or absence of IL-4 to polarize the BMDMs towards an M2 phenotype. The mRNA expression levels of the M2 markers IL10, CD206, PPARγ, STAT6 and IRF4 were measured by qPCR (n = 6). Data are mean ± SEM relative to WT Control (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

Mentions: We saw a significant increase in two anti-inflammatory markers, IL-10 and IL-5, in the plasma of the MNK2-KO/HFD mice compared to WT/HFD mice (Fig. 7a,b). We therefore investigated the abilities of BMDMs from WT and MNK2-KO mice to polarize towards an M2 anti-inflammatory phenotype. Interestingly, we found that under control conditions, MNK2-KO BMDMs had elevated levels of IL-10 and PPARγ compared to WT BMDMs. All M2 markers examined were increased more in these cells than in WT-BMDMs after 24 h stimulation with IL-4 (Fig. 7c–g). The data suggest that MNK2-KO macrophages have a higher tendency towards an anti-inflammatory phenotype.


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 marker genes in BMDMs from WT and MNK2-KO mice.(a,b) Plasma levels of IL-5 and IL-10 from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice were measured by ELISA (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05. (c–f) BMDMs isolated from WT or MNK2-KO mice were cultured for 24 h in the presence or absence of IL-4 to polarize the BMDMs towards an M2 phenotype. The mRNA expression levels of the M2 markers IL10, CD206, PPARγ, STAT6 and IRF4 were measured by qPCR (n = 6). Data are mean ± SEM relative to WT Control (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **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

f7: Analysis of marker genes in BMDMs from WT and MNK2-KO mice.(a,b) Plasma levels of IL-5 and IL-10 from chow-fed and HFD-fed WT, MNK1-KO and MNK2-KO mice were measured by ELISA (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05. (c–f) BMDMs isolated from WT or MNK2-KO mice were cultured for 24 h in the presence or absence of IL-4 to polarize the BMDMs towards an M2 phenotype. The mRNA expression levels of the M2 markers IL10, CD206, PPARγ, STAT6 and IRF4 were measured by qPCR (n = 6). Data are mean ± SEM relative to WT Control (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Mentions: We saw a significant increase in two anti-inflammatory markers, IL-10 and IL-5, in the plasma of the MNK2-KO/HFD mice compared to WT/HFD mice (Fig. 7a,b). We therefore investigated the abilities of BMDMs from WT and MNK2-KO mice to polarize towards an M2 anti-inflammatory phenotype. Interestingly, we found that under control conditions, MNK2-KO BMDMs had elevated levels of IL-10 and PPARγ compared to WT BMDMs. All M2 markers examined were increased more in these cells than in WT-BMDMs after 24 h stimulation with IL-4 (Fig. 7c–g). The data suggest that MNK2-KO macrophages have a higher tendency towards an anti-inflammatory phenotype.

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