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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

HFD-fed MNK1- or MNK2-KO mice show better glucose tolerance.(a) Glucose tolerance test. After 15 weeks on either chow or the HFD, mice were fasted overnight before receiving an intraperitoneal injection of 2 g/kg glucose, and blood samples were taken at the indicated times (n = 6–21). Data are mean ± SEM. (b) Area under the curve calculations (AUC) (n = 6–21). Data are mean ± SEM (two-way ANOVA with Tukey’s post-test). (c) Insulin action test. After 20 weeks on either chow or HFD, the mice were fasted overnight before receiving an intraperitoneal injection of 0.75 U/kg insulin, and blood samples were taken at 30 min (n = 3–4). Data are mean ± SEM (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01.
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f4: HFD-fed MNK1- or MNK2-KO mice show better glucose tolerance.(a) Glucose tolerance test. After 15 weeks on either chow or the HFD, mice were fasted overnight before receiving an intraperitoneal injection of 2 g/kg glucose, and blood samples were taken at the indicated times (n = 6–21). Data are mean ± SEM. (b) Area under the curve calculations (AUC) (n = 6–21). Data are mean ± SEM (two-way ANOVA with Tukey’s post-test). (c) Insulin action test. After 20 weeks on either chow or HFD, the mice were fasted overnight before receiving an intraperitoneal injection of 0.75 U/kg insulin, and blood samples were taken at 30 min (n = 3–4). Data are mean ± SEM (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01.

Mentions: To assess directly the effect of the HFD on glucose handling in WT and MNK2-KO animals, we performed a glucose tolerance test (GTT). In the GTT, chow-fed MNK1- or MNK2-KO mice showed a similar response to WT animals indicating that the MNKs do not affect glucose handling under chow-fed conditions. However, MNK1- or MNK2-KO/HFD mice showed markedly lower blood glucose levels at all times after glucose administration relative to WT/HFD mice, which did show the expected marked impairment in glucose handling (Fig. 4a,b). Thus, knock-out of either MNK1 or MNK2 protects mice against HFD-induced glucose intolerance.


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)

HFD-fed MNK1- or MNK2-KO mice show better glucose tolerance.(a) Glucose tolerance test. After 15 weeks on either chow or the HFD, mice were fasted overnight before receiving an intraperitoneal injection of 2 g/kg glucose, and blood samples were taken at the indicated times (n = 6–21). Data are mean ± SEM. (b) Area under the curve calculations (AUC) (n = 6–21). Data are mean ± SEM (two-way ANOVA with Tukey’s post-test). (c) Insulin action test. After 20 weeks on either chow or HFD, the mice were fasted overnight before receiving an intraperitoneal injection of 0.75 U/kg insulin, and blood samples were taken at 30 min (n = 3–4). Data are mean ± SEM (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4834573&req=5

f4: HFD-fed MNK1- or MNK2-KO mice show better glucose tolerance.(a) Glucose tolerance test. After 15 weeks on either chow or the HFD, mice were fasted overnight before receiving an intraperitoneal injection of 2 g/kg glucose, and blood samples were taken at the indicated times (n = 6–21). Data are mean ± SEM. (b) Area under the curve calculations (AUC) (n = 6–21). Data are mean ± SEM (two-way ANOVA with Tukey’s post-test). (c) Insulin action test. After 20 weeks on either chow or HFD, the mice were fasted overnight before receiving an intraperitoneal injection of 0.75 U/kg insulin, and blood samples were taken at 30 min (n = 3–4). Data are mean ± SEM (2-tailed, unpaired Student’s t test) *P < 0.05, **P < 0.01.
Mentions: To assess directly the effect of the HFD on glucose handling in WT and MNK2-KO animals, we performed a glucose tolerance test (GTT). In the GTT, chow-fed MNK1- or MNK2-KO mice showed a similar response to WT animals indicating that the MNKs do not affect glucose handling under chow-fed conditions. However, MNK1- or MNK2-KO/HFD mice showed markedly lower blood glucose levels at all times after glucose administration relative to WT/HFD mice, which did show the expected marked impairment in glucose handling (Fig. 4a,b). Thus, knock-out of either MNK1 or MNK2 protects mice against HFD-induced glucose intolerance.

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