| Title: | TNIK is a conserved regulator of glucose and lipid metabolism in obesity |
| Journal: | Science Advances |
| Published: | 9 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37556547/ |
| DOI: | https://doi.org/10.1126/sciadv.adf7119 |
| URL: | https://www.science.org/doi/pdf/10.1126/sciadv.adf7119?download=true |
Publication 10179
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
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.</p>
20 Authors
- T C Phung Pham
- Lucile Dollet
- Mona S Ali
- Steffen H Raun
- Lisbeth L V Møller
- Abbas Jafari
- Nicholas Ditzel
- Nicoline R Andersen
- Andreas M Fritzen
- Zachary Gerhart-Hines
- Bente Kiens
- Anu Suomalainen
- Stephen J Simpson
- Morten Salling Olsen
- Arnd Kieser
- Peter Schjerling
- Anni I Nieminen
- Erik A Richter
- Essi Havula
- Lykke Sylow
Enabling scientific discoveries that improve human health