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

MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways
MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways
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.
Moore, C.E.J.
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Pickford, J
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Cagampang, F.R.
7cf57d52-4a65-4554-8306-ed65226bc50e
Stead, R.S.
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Tian, S.
c5c74ca2-2ec4-4f80-9b1a-78e45e8c87ff
Zhao, X.
c32d0dd5-3ac6-4c9c-b41e-95baa08c7472
Tang, X.
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Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c
Proud, C.
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Moore, C.E.J.
ce0800e4-610b-4e2e-9763-ae982eab2901
Pickford, J
7f80b029-87ea-40bc-a71b-79ae5f522b81
Cagampang, F.R.
7cf57d52-4a65-4554-8306-ed65226bc50e
Stead, R.S.
a481dba4-a1ed-4d98-ad59-a6457d069928
Tian, S.
c5c74ca2-2ec4-4f80-9b1a-78e45e8c87ff
Zhao, X.
c32d0dd5-3ac6-4c9c-b41e-95baa08c7472
Tang, X.
66e53614-a4c2-43c7-856d-a448f90d478c
Byrne, C.
1370b997-cead-4229-83a7-53301ed2a43c
Proud, C.
582e88a7-6c0e-43e4-ad23-fb6e9045f800

Moore, C.E.J., Pickford, J, Cagampang, F.R., Stead, R.S., Tian, S., Zhao, X., Tang, X., Byrne, C. and Proud, C. (2016) MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways. Scientific Reports, 6, [23476]. (doi:10.1038/srep23476).

Record type: Article

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.

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Science Report (Uncorrected proofs SREP23476).pdf - Accepted Manuscript
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More information

Accepted/In Press date: 7 March 2016
e-pub ahead of print date: 18 April 2016
Published date: April 2016
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 391606
URI: http://eprints.soton.ac.uk/id/eprint/391606
PURE UUID: e81affcf-cace-48ba-a12d-d2cbc72db981
ORCID for F.R. Cagampang: ORCID iD orcid.org/0000-0003-4404-9853
ORCID for C. Byrne: ORCID iD orcid.org/0000-0001-6322-7753

Catalogue record

Date deposited: 13 Apr 2016 10:32
Last modified: 27 Jan 2020 13:39

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