TNIK is a conserved regulator of glucose and lipid metabolism in obesity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TNIK is a conserved regulator of glucose and lipid metabolism in obesity. / Pham, Tang Cam Phung; Dollet, Lucile; Ali, Mona Sadek; Raun, Steffen Henning; Møller, Lisbeth Liliendal Valbjørn; Jafari, Abbas; Ditzel, Nicholas; Andersen, Nicoline Resen; Fritzen, Andreas Mæchel; Gerhart-Hines, Zachary; Kiens, Bente; Suomalainen, Anu; Simpson, Stephen J; Salling Olsen, Morten; Kieser, Arnd; Schjerling, Peter; Nieminen, Anni I; Richter, Erik A.; Havula, Essi; Sylow, Lykke.
I: Science Advances, Bind 9, Nr. 32, eadf7119, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - TNIK is a conserved regulator of glucose and lipid metabolism in obesity
AU - Pham, Tang Cam Phung
AU - Dollet, Lucile
AU - Ali, Mona Sadek
AU - Raun, Steffen Henning
AU - Møller, Lisbeth Liliendal Valbjørn
AU - Jafari, Abbas
AU - Ditzel, Nicholas
AU - Andersen, Nicoline Resen
AU - Fritzen, Andreas Mæchel
AU - Gerhart-Hines, Zachary
AU - Kiens, Bente
AU - Suomalainen, Anu
AU - Simpson, Stephen J
AU - Salling Olsen, Morten
AU - Kieser, Arnd
AU - Schjerling, Peter
AU - Nieminen, Anni I
AU - Richter, Erik A.
AU - Havula, Essi
AU - Sylow, Lykke
N1 - CURIS 2023 NEXS 179
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Animals
KW - Mice
KW - Diabetes Mellitus, Type 2/genetics
KW - Glucose/metabolism
KW - Insulin Resistance
KW - Lipid Metabolism
KW - Lipids
KW - Liver/metabolism
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Obesity/genetics
KW - Protein Serine-Threonine Kinases/metabolism
U2 - 10.1126/sciadv.adf7119
DO - 10.1126/sciadv.adf7119
M3 - Journal article
C2 - 37556547
VL - 9
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 32
M1 - eadf7119
ER -
ID: 362054269