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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

Responses of MNK1-KO and MNK2-KO mice to high fat feeding.(a) Bodyweight of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a high fat diet (HFD) (45% kcal from fat) (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ****P < 0.0001. (b) Gonadal adipose tissue weight expressed as a percentage of bodyweight (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (c) Representative images showing gonadal fat depots from WT, MNK1-KO and MNK2-KO mice after 20 weeks HFD. (d) Fasting blood glucose of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, ***P < 0.001. (e) Fasting plasma insulin levels of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 3–5). Data are mean ± SEM. (f) Homeostasis model assessment of insulin resistance (HOMA-IR) as an index of insulin resistance.
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f2: Responses of MNK1-KO and MNK2-KO mice to high fat feeding.(a) Bodyweight of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a high fat diet (HFD) (45% kcal from fat) (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ****P < 0.0001. (b) Gonadal adipose tissue weight expressed as a percentage of bodyweight (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (c) Representative images showing gonadal fat depots from WT, MNK1-KO and MNK2-KO mice after 20 weeks HFD. (d) Fasting blood glucose of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, ***P < 0.001. (e) Fasting plasma insulin levels of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 3–5). Data are mean ± SEM. (f) Homeostasis model assessment of insulin resistance (HOMA-IR) as an index of insulin resistance.

Mentions: As expected, feeding wild-type (WT) C57BL/6J mice an HFD led to increased bodyweight and gonadal fat (Fig. 2a–c). High fat-fed MNK1-KO mice showed similar increases in body and gonadal fat weight to WT mice on the HFD (Fig. 2a–c). In contrast, feeding MNK2-KO mice the same HFD caused smaller increases in body weight and fat. In WT mice, the HFD also caused marked increases in circulating levels of glucose and insulin (Fig. 2d,e, respectively). Such increases were markedly blunted in both MNK1-KO and MNK2-KO animals on the HFD, indicating attenuation of the adverse effects of the HFD. In chow-fed animals, basal glucose and insulin levels were similar to those in WT mice. We observed no differences in food intake of MNK-KO mice vs. wild-type controls.


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)

Responses of MNK1-KO and MNK2-KO mice to high fat feeding.(a) Bodyweight of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a high fat diet (HFD) (45% kcal from fat) (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ****P < 0.0001. (b) Gonadal adipose tissue weight expressed as a percentage of bodyweight (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (c) Representative images showing gonadal fat depots from WT, MNK1-KO and MNK2-KO mice after 20 weeks HFD. (d) Fasting blood glucose of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, ***P < 0.001. (e) Fasting plasma insulin levels of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 3–5). Data are mean ± SEM. (f) Homeostasis model assessment of insulin resistance (HOMA-IR) as an index of insulin resistance.
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Related In: Results  -  Collection

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f2: Responses of MNK1-KO and MNK2-KO mice to high fat feeding.(a) Bodyweight of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a high fat diet (HFD) (45% kcal from fat) (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ****P < 0.0001. (b) Gonadal adipose tissue weight expressed as a percentage of bodyweight (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. (c) Representative images showing gonadal fat depots from WT, MNK1-KO and MNK2-KO mice after 20 weeks HFD. (d) Fasting blood glucose of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 6–9). Data are mean ± SEM (two-way ANOVA followed by Tukey’s post test) *P < 0.05, ***P < 0.001. (e) Fasting plasma insulin levels of WT, MNK1-KO and MNK2-KO mice after 20 weeks on either chow or a HFD (n = 3–5). Data are mean ± SEM. (f) Homeostasis model assessment of insulin resistance (HOMA-IR) as an index of insulin resistance.
Mentions: As expected, feeding wild-type (WT) C57BL/6J mice an HFD led to increased bodyweight and gonadal fat (Fig. 2a–c). High fat-fed MNK1-KO mice showed similar increases in body and gonadal fat weight to WT mice on the HFD (Fig. 2a–c). In contrast, feeding MNK2-KO mice the same HFD caused smaller increases in body weight and fat. In WT mice, the HFD also caused marked increases in circulating levels of glucose and insulin (Fig. 2d,e, respectively). Such increases were markedly blunted in both MNK1-KO and MNK2-KO animals on the HFD, indicating attenuation of the adverse effects of the HFD. In chow-fed animals, basal glucose and insulin levels were similar to those in WT mice. We observed no differences in food intake of MNK-KO mice vs. wild-type controls.

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