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![Induced Ablation of Skeletal Muscle-Specific Estrogen Receptor-Alpha in Adult Female Mice Increased the Susceptibility to Develop Skeletal Muscle Inflammation and Glucose Intolerance Under Chronic Lipid Overload için kapak resmi Induced Ablation of Skeletal Muscle-Specific Estrogen Receptor-Alpha in Adult Female Mice Increased the Susceptibility to Develop Skeletal Muscle Inflammation and Glucose Intolerance Under Chronic Lipid Overload için kapak resmi](/client/assets/d79c3e4af2b6d196/ctx/images/no_image.png)
Induced Ablation of Skeletal Muscle-Specific Estrogen Receptor-Alpha in Adult Female Mice Increased the Susceptibility to Develop Skeletal Muscle Inflammation and Glucose Intolerance Under Chronic Lipid Overload
Başlık:
Induced Ablation of Skeletal Muscle-Specific Estrogen Receptor-Alpha in Adult Female Mice Increased the Susceptibility to Develop Skeletal Muscle Inflammation and Glucose Intolerance Under Chronic Lipid Overload
Yazar:
Inigo, Melissa Mae Raval, author.
ISBN:
9780438156913
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (182 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Özet:
Skeletal muscle-specific ERalpha appears to play important roles in regulating skeletal muscle glucose and lipid homeostasis. The overall aim of this dissertation was to determine whether skeletal muscle-specific ERalpha is critical for maintaining metabolic function under conditions of lipid overload. To further advance our understanding of skeletal muscle-specific ERalpha, this study integrated in vivo and in vitro loss-of-function approaches by generating a novel inducible skeletal muscle-specific ERalpha knockout mouse model (ERalphaKOism) and by silencing ERalpha in human myotubes using an adenovirus-driven ERalphashRNA. The overarching hypothesis is that induced ablation of skeletal muscle-specific ERalpha increased the susceptibility to high fat diet (HFD)-induced metabolic dysfunction. ERalphaKOism mice exhibited similar adiposity after acute and chronic HFD treatments compared to WT mice, for both females and males. Indirect calorimetry revealed that energy expenditure was similar between female WT and ERalphaKOism mice, even when exposed to acute and chronic HFD treatments. Male ERalphaKOism mice exhibited minimally greater energy expenditure after chronic HFD treatment compared to male WT mice, regardless of diet. Spontaneous cage activity was similar between diet-matched WT and ERalphaKOism mice for both sexes, even after acute and chronic HFD treatment. Analysis of glucose dynamics revealed that female ERalphaKOism-HFD exhibited greater glucose intolerance than WT-HFD after chronic HFD treatment. Ex vivo skeletal muscle glucose uptake was similar between female WT and ERalphaKOism mice, although GLUT4 protein content was lower in skeletal muscle of female ERalphaKOism, regardless of diet. Markers of pro-inflammation were also elevated in female ERalphaKO ism mice, regardless of diet. Analysis of mitochondrial respiratory capacity, oxidative phosphorylation efficiency, and H2O2 emission potential in permeabilized skeletal muscle fibers, revealed that skeletal muscle mitochondrial function was similar between WT and ERalphaKO ism for both sexes. In human skeletal myotubes sourced from healthy and obese-insulin resistant adult women, ATP production rate was minimally lower in myotubes transduced with ERalphashRNA compared to scrambled-shRNA (control) myotubes. Overall, the data suggest that skeletal muscle ERalpha is critical for maintaining glucose tolerance in females on a chronic HFD and regulating skeletal muscle inflammation.
Notlar:
School code: 0600
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(697140.1) | 697140-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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