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Pham, T.C.P.* ; Dollet, L.* ; Ali, M.S.* ; Raun, S.H.* ; Møller, L.L.V.* ; Jafari, A.* ; Ditzel, N.* ; Andersen, N.R.* ; Fritzen, A.M.* ; Gerhart-Hines, Z.* ; Kiens, B.* ; Suomalainen, A.* ; Simpson, S.J.* ; Salling Olsen, M.* ; Kieser, A. ; Schjerling, P.* ; Nieminen, A.I.* ; Richter, E.A.* ; Havula, E.* ; Sylow, L.*

TNIK is a conserved regulator of glucose and lipid metabolism in obesity.

Sci. Adv. 9:eadf7119 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
Obesity and type 2 diabetes (T2D) are growing health challenges with unmet treatment needs. Traf2- and NCK-interacting protein kinase (TNIK) is a recently identified obesity- and T2D-associated gene with unknown functions. We show that TNIK governs lipid and glucose homeostasis in Drosophila and mice. Loss of the Drosophila ortholog of TNIK, misshapen, altered the metabolite profiles and impaired de novo lipogenesis in high sugar-fed larvae. Tnik knockout mice exhibited hyperlocomotor activity and were protected against diet-induced fat expansion, insulin resistance, and hepatic steatosis. The improved lipid profile of Tnik knockout mice was accompanied by enhanced skeletal muscle and adipose tissue insulin-stimulated glucose uptake and glucose and lipid handling. Using the T2D Knowledge Portal and the UK Biobank, we observed associations of TNIK variants with blood glucose, HbA1c, body mass index, body fat percentage, and feeding behavior. These results define an untapped paradigm of TNIK-controlled glucose and lipid metabolism.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Skeletal-muscle; Adipose-tissue; Insulin Sensitivity; Resistance; Pathway; Family; Member; Roles; Ampk
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 9, Issue: 32, Pages: , Article Number: eadf7119 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Research Unit Signaling and Translation (SAT)
Grants Independent Research Fund Denmark
European Union's Horizon 2020 research and innovation programme, Marie Sklodowska-Curie
Finnish Diabetes Research Foundation
Novo Nordisk Foundation
Maud Kuistila Foundation
German Research Foundation, Collaborative Research Center
Lundbeck Foundation
Academy of Finland
Sigrid Juselius Foundation
Jane and Aatos Erkko Foundation
Hallas-Moller Emerging Investigator Novo Nordisk Foundation
Orion Research Foundation