title: MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways.
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.
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.|Nutrition and Metabolism, South Australian Health &Medical Research Institute, North Terrace, Adelaide, SA5000, Australia.
authors.forename: C E J
authors.initials: CE
authors.lastname: Moore
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Pickford
authors.affiliation: Institute of Developmental Sciences, University of Southampton, Faculty of Medicine, Southampton SO16 6YD, United Kingdom.
authors.forename: F R
authors.initials: FR
authors.lastname: Cagampang
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.
authors.forename: R L
authors.initials: RL
authors.lastname: Stead
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.|Nutrition and Metabolism, South Australian Health &Medical Research Institute, North Terrace, Adelaide, SA5000, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Tian
authors.affiliation: Nutrition and Metabolism, South Australian Health &Medical Research Institute, North Terrace, Adelaide, SA5000, Australia.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry &Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 China.
authors.forename: X
authors.initials: X
authors.lastname: Tang
authors.affiliation: Nutrition and Metabolism, University of Southampton, Faculty of Medicine, Southampton SO16 6YD, United Kingdom.|Southampton National Institute for Health Research, Biomedical Research Centre, University Hospital, Southampton, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Byrne
authors.affiliation: Centre for Biological Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom.|Nutrition and Metabolism, South Australian Health &Medical Research Institute, North Terrace, Adelaide, SA5000, Australia.|School of Biological Sciences, University of Adelaide, Adelaide SA 5005, Australia.
authors.forename: C G
authors.initials: CG
authors.lastname: Proud
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects*; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C106281:Mknk1 protein, mouse; C106282:Mknk2 protein, mouse; D017346:Protein Serine-Threonine Kinases