Examinando por Autor "Jensen, Thomas E."

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    Muscle-specific AXIN1 and AXIN2 double knockout does not alter AMPK/mTORC1 signalling or glucose metabolism
    (Wiley; The Physiological Society, 2025-07-01) Persson, Kaspar W.; Meneses-Valdés, Roberto; Andersen, Nicoline R.; Pedersen, Frederik S.; Gallo, Samantha; Hesselager, Sofie A.; Henríquez-Olguín, Carlos; Jensen, Thomas E.
    AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are crucial kinase signalling hubs that regulate the balance between catabolism and anabolism in skeletal muscle. The scaffold protein AXIN1 has been proposed to regulate the switch between these pathways and be required for GLUT4 translocation in skeletal muscle and adipocyte cell lines. Muscle-specific AXIN1 knockout (KO) mice exhibit no discernable phenotype, possibly due to compensation by AXIN2 upon AXIN1 loss. Thus we generated and characterized muscle-specific inducible AXIN1 and AXIN2 double knockout (dKO) mice. Surprisingly AXIN1/2 dKO mice displayed normal AMPK and mTORC1 signalling and glucose uptake in response to 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), insulin and in situ muscle contraction. These findings suggest that AXIN proteins are not essential for the regulation of AMPK and mTORC1 signalling or glucose uptake in skeletal muscle. This study challenges the previously indicated critical roles of AXIN1 in exercise-stimulated AMPK activation and GLUT4-mediated glucose uptake in skeletal muscle. KEY POINTS: Phenotyping of tamoxifen-inducible muscle-specific AXIN1/2 double knockout (dKO) mice. We find no evidence for AXIN-dependent AMPK or mTORC1 regulation in skeletal muscle by insulin, AMPK activation or contraction. Glucose uptake regulation by insulin and AMPK activation is normal in AXIN1/2 dKO mice.
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    NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging
    (Elsevier, 0022-06-25) Chubanava, Sabina; Karavaeva, Iuliia; Ehrlich, Amy M.; Justicia, Roger M.; Basse, Astrid L.; Kulik, Ivan; Dalbram, Emilie; Ahwazi, Danial; Heaselgrave, Samuel R.; Trost, Kajetan; Stocks, Ben; Hodek, Ondrej; Rodrigues, Raissa N.; Havelund, Jesper F.; Schlabs, Farina L.; Larsen, Steen; Yonamine, Caio Y.; Henríquez-Olguín, Carlos; Giustarini, Daniela; Rossi, Ranieri; Gerhart-Hines, Zachary; Moritz, Thomas; Zierath, Juleen R.; Sakamoto, Kei; Jensen, Thomas E.; Færgeman, Nils J.; Lavery, Gareth G.; Deshmukh, Atul S.; Treebak, Jonas T.
    Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD+ abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.