Einfluss des Wachstums-Differenzierungs-Faktors-15 (GDF-15) auf die Morphologie des M. triceps surae (Mm. gastrocnemius und soleus) bei Apo E-knockout- und Wildtyp-Mäusen unter Standardfütterung
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2025-09-29
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Abstract
Growth differentiation factor-15 (GDF-15) is a multifunctional cytocine of the TGF-β family. It has first been identified in 1997 and has since gained increas-ing scientific and clinical interest. GDF-15 plays an essential role particularly in cardiovascular diseases, the regulation of energy balance as well as cachexia. Various cell types, including cardiomyocytes, adipocytes and muscle cells can express and secrete GDF-15. Under stress exposure, during inflammation, tu-mor diseases, cellular stress, and hypoxia, the normally low serum concentra-tion of GDF-15 can increase up to 100-fold. This causes a strong correlation between elevated GDF-15 concentrations and diseases such as diabetes melli-tus, cardiovascular diseases and tumor cachexia.
Even though GDF-15 performs various essential functions within the organism, little is known about the exact influence of GDF-15 within skeletal muscle. In the present study, the impact of GDF-15 deficiency on the M. triceps surae (Mm. gastrocnemius and soleus) was investigated regarding the expression of in-flammatory, angiogenic, apoptotic, and atrophic proteins/cytokines as well as on glycogen metabolism and the innervation of skeletal muscle in mice after the administration of a standard chow. Four mouse genotypes were examined: wild type, GDF-15, Apo E-/- and GDF-15 -/-/Apo E-/- mice.
The following are exclusively the significant results of the GDF-15 deficiency:
GDF-15-/-/Apo E-/--mice had a significantly higher weight and a a significantly shorter tibia than Apo E-/- -mice. In soleus and gastrocnemius muscles the fiber cross-sectional areas of GDF-15-/-/Apo E-/--mice were significantly larger than those of Apo E-/--mice, whereas the fiber densities of GDF-15-/-/Apo E-/- -mice in soleus and gastrocnemius muscles were significantly lower. In soleus muscle GDF-15-/-/Apo E-/- -mice had a significantly larger fiber type I cross-sectional area as well as a significantly lower percentage of fiber type I compared to Apo E-/--mice. In soleus muscle, GDF-15-/- -mice exhibited significantly more glyco-gen-poor fibers and significantly fewer glycogen-rich fibers compared to wild-type mice. In gastrocnemius muscle, GDF-15-/- -mice displayed significantly fewer glycogen-free and glycogen-rich fibers, but significantly more glycogen-poor fibers compared to wild-type mice. GDF-15-/- -mice had a significantly higher number of MuRF-1+ cells in the soleus muscle compared to wild-type mice. GDF-15-/- /Apo E-/- -mice exhibited a significantly higher number of MuRF-1+-cells in soleus muscle compared to Apo E-/- -mice. Concerning fiber type I, GDF-15-/- -mice exhibited a significantly lower number of capillary contacts compared to wild-type mice. Regarding fiber type IIb, GDF-15-/-/Apo E-/- -mice had a significantly lower number of capillary contacts compared to Apo E-/- -mice. GDF-15-/-/Apo E-/- -mice exhibited significantly more interstitial COX-2+ -cells in soleus and gastrocnemius muslces compared to Apo E-/- -mice. GDF-15-/-/Apo E-/- -mice showed a significantly lower number of COX-2+-muscle fibers in gastrocnemius muscle than Apo E-/- -mice. GDF-15-/--mice showed a higher number of IL-1β+ cells per muscle fiber in soleus and gastrocnemius muslces than wild-type mice. GDF-15-/-/Apo E-/- -mice had a significantly higher number of CD68+ -cells per muscle fiber than Apo E-/- -mice.
Our results indicate that GDF-15 deficiency, after 30 weeks of a standard diet, can affect body weight, tibial length, morphology, glycogen content, as well as proteins relevant to inflammation, angiogenesis and atrophy in triceps surae muscle of mice. Interestingly, GDF-15 is capable of affecting fiber surface area and number of the entire triceps surae muscle, independent of MuRF-1 or other examined factors. Furthermore, our results show that GDF-15 deficiency in Apo E-deficient mice, an established mouse model für artherosclerosis, leads to additional significant results. GDF-15 deficiency in Apo E-deficient mice leads to a stronger anabolic effect on body weight, a significant inhibitory effect on bone growth, hypertrophic type I muscle fibers, and greater pro-inflammatory effects compared to Apo E-competent mice. Future investigations about the impact of GDF-15 deficiency on other organs and tissues in relation to atherosclerosis could therefore be substantial.
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Issued: 2025-09-29
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FB20:Medizin
Language
de
Keywords
GDF-15M.triceps suraeStandardfutterApo E knockoutMorphologie
DFG-subjects
201-03 Zellbiologie
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Anna Brockmann: Einfluss des Wachstums-Differenzierungs-Faktors-15 (GDF-15) auf die Morphologie des M. triceps surae (Mm. gastrocnemius und soleus) bei Apo E-knockout- und Wildtyp-Mäusen unter Standardfütterung. : 2025-09-29.
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