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035 a| (Sirsi) o1037952022;

035 a| (OCoLC)1037952022;

049 a| EREE;

100 1 a| Iñigo, Melissa Mae Raval,e| author.?| UNAUTHORIZED;

245 10 a| 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 /c| by Melissa Mae Raval Iñigo.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2018.;

300 a| 182 pages :b| color illustrations.;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 9.61 MB2| rda;

490 1 a| ECU Brody School of Medicine dissertation;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| Ph.D.c| East Carolina Universityd| 2018.;

500 a| Presented to the faculty of the Department of Physiology;

500 a| Advisor: Espen E. Spangenburg;

500 a| Title from PDF t.p. (viewed August 22, 2018).;

520 3 a| Skeletal muscle-specific ER[alpha] 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 ER[alpha] is critical for maintaining metabolic function under conditions of lipid overload. To further advance our understanding of skeletal muscle-specific ER[alpha], this study integrated in vivo and in vitro loss-of-function approaches by generating a novel inducible skeletal muscle-specific ER[alpha] knockout mouse model (ER[alpha]KOism) and by silencing ER[alpha] in human myotubes using an adenovirus-driven ER[alpha]shRNA. The overarching hypothesis is that induced ablation of skeletal muscle-specific ER[alpha] increased the susceptibility to high fat diet (HFD)-induced metabolic dysfunction. ER[alpha]KOism 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 ER[alpha]KOism mice, even when exposed to acute and chronic HFD treatments. Male ER[alpha]KOism 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 ER[alpha]KOism mice for both sexes, even after acute and chronic HFD treatment. Analysis of glucose dynamics revealed that female ER[alpha]KOism-HFD exhibited greater glucose intolerance than WT-HFD after chronic HFD treatment. Ex vivo skeletal muscle glucose uptake was similar between female WT and ER[alpha]KOism mice, although GLUT4 protein content was lower in skeletal muscle of female ER[alpha]KOism, regardless of diet. Markers of pro-inflammation were also elevated in female ER[alpha]KOism 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 ER[alpha]KOism 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 ER[alpha]shRNA compared to scrambled-shRNA (control) myotubes. Overall, the data suggest that skeletal muscle ER[alpha] is critical for maintaining glucose tolerance in females on a chronic HFD and regulating skeletal muscle inflammation.;

504 a| Includes bibliographical references.;

650 2 a| Estrogen Receptor alpha.=| ^A1362244;

650 2 a| Mice.=| ^A921375;

650 2 a| Female.=| ^A1058014;

650 2 a| Animals.=| ^A919771;

650 2 a| estrogen receptor alpha, human.?| UNAUTHORIZED;

650 2 a| Glucose Intolerance.=| ^A1362218;

650 2 a| Myositis.=| ^A1345644;

650 2 a| Muscle, Skeletal.=| ^A928794;

650 2 a| Inflammation.=| ^A917595;

650 2 a| Lipids.=| ^A917865;

653 a| metabolism;

653 a| mitochondrial respiration;

653 a| OXPHOS efficiency;

653 a| H2O2 emission potential;

653 a| glucose tolerance;

700 1 a| Spangenburg, Espen E.,e| degree supervisor.=| ^A1252473;

710 2 a| East Carolina University.b| Department of Physiology.?| UNAUTHORIZED;

830 0 a| ECU Brody School of Medicine dissertation.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/6785;

949 o| wjh;

994 a| C0b| ERE;

096 a| WP 522;

596 a| 1 4;

998 a| 4867554;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4867554-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 5/31/2018x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4867554-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 5/31/2018x| ETDz| HERESOURCE;

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 / by Melissa Mae Raval Iñigo.

Author/creator	Iñigo, Melissa Mae Raval author.
Other author	Spangenburg, Espen E., degree supervisor.
Other author	East Carolina University. Department of Physiology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2018.
Description	182 pages : color illustrations.
Supplemental Content	Access via ScholarShip
Subjects	Estrogen Receptor alpha. Mice. Female. Animals. estrogen receptor alpha, human. Glucose Intolerance. Myositis. Muscle, Skeletal. Inflammation. Lipids.

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Skeletal muscle-specific ER[alpha] 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 ER[alpha] is critical for maintaining metabolic function under conditions of lipid overload. To further advance our understanding of skeletal muscle-specific ER[alpha], this study integrated in vivo and in vitro loss-of-function approaches by generating a novel inducible skeletal muscle-specific ER[alpha] knockout mouse model (ER[alpha]KOism) and by silencing ER[alpha] in human myotubes using an adenovirus-driven ER[alpha]shRNA. The overarching hypothesis is that induced ablation of skeletal muscle-specific ER[alpha] increased the susceptibility to high fat diet (HFD)-induced metabolic dysfunction. ER[alpha]KOism 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 ER[alpha]KOism mice, even when exposed to acute and chronic HFD treatments. Male ER[alpha]KOism 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 ER[alpha]KOism mice for both sexes, even after acute and chronic HFD treatment. Analysis of glucose dynamics revealed that female ER[alpha]KOism-HFD exhibited greater glucose intolerance than WT-HFD after chronic HFD treatment. Ex vivo skeletal muscle glucose uptake was similar between female WT and ER[alpha]KOism mice, although GLUT4 protein content was lower in skeletal muscle of female ER[alpha]KOism, regardless of diet. Markers of pro-inflammation were also elevated in female ER[alpha]KOism 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 ER[alpha]KOism 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 ER[alpha]shRNA compared to scrambled-shRNA (control) myotubes. Overall, the data suggest that skeletal muscle ER[alpha] is critical for maintaining glucose tolerance in females on a chronic HFD and regulating skeletal muscle inflammation.
General note	Presented to the faculty of the Department of Physiology
General note	Advisor: Espen E. Spangenburg
General note	Title from PDF t.p. (viewed August 22, 2018).
Dissertation note	Ph.D. East Carolina University 2018.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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 / by Melissa Mae Raval Iñigo.

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