Tools

LEADER 04903cam 2200565Ii 4500

001 on1021186444;

003 OCoLC;

005 20180511100959.0;

006 m o d ;

007 cr unu||||||||;

008 180201s2017 ncua obm 000 0 eng d;

035 a| (Sirsi) o1021186444;

035 a| (OCoLC)1021186444;

049 a| EREE;

100 1 a| Robison, E. Madison,e| author.?| UNAUTHORIZED;

245 14 a| The influence of diet-induced obesity and N-3 fatty acids on the cardiac mitochondrial phospholipidome and respiratory activity /c| by E. Madison Robison.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2017.;

300 a| 239 pages :b| illustrations (some color).;

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 13.99 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| 2017.;

500 a| Presented to the faculty of the Department of Biochemistry and Molecular Biology;

500 a| Advisor: Saame R. Shaikh;

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

520 3 a| Cardiac mitochondrial phospholipids, notably cardiolipin (CL), regulate inner mitochondrial membrane (IMM) organization and protein function, particularly the enzymes associated with respiration. In a range of metabolic diseases, CL and other phospholipids undergo acyl chain remodeling, which would presumably impair respiratory activity. In diet-induced obesity, the influence of cardiac remodeling on respiratory enzyme activity and mitochondrial respiration is poorly studied. Thus, we first established the effect of diet-induced obesity on the mitochondrial phospholipidome and subsequent influences on mitochondrial function using two different dietary models. Surprisingly, the high fat diet and western diet remodeled the phospholipidome, but both obesogenic diets had no influence on cardiac mitochondrial supercomplex formation, respiratory enzyme activities, or respiration. Therefore, we next investigated how extremely remodeling with dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) in the context of obesity, would influence the mitochondrial phospholipidome and thereby respiration. The rationale for focusing on n-3 PUFAs was that these fatty acids are generally considered cardioprotective but paradoxically are elevated in several metabolic diseases. Dietary supplementation with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) extensively remodeled the phospholipidome. Particularly, CL acyl chains were remodeled to include DHA at the loss of linoleic acid, which is incorporated into 90% of CL species. Strikingly, supplementation with DHA reduced the activities of several respiratory enzymes, although overall respiration was not affected. We tested the hypothesis that the reduction in enzymatic activity with DHA was driven by the replacement of linoleic acid with DHA in CL species. Indeed, fusion of linoleic acid to mitochondria isolated from DHA-fed mice, rescued the impairments in the CL lipidome and thereby several respiratory complex activities. These results suggest that increased DHA in the myocardium in differing diseases may be targeting enzymatic activity. Taken together, the data establish that obesity by itself in mice does not disrupt respiratory enzyme activity despite remodeling of CL acyl chains. However, extensive remodeling with n-3 PUFAs has a strong influence. Finally, this study has implications for future nutritional studies on the balance between linoleic acid and n-3 PUFAs in the heart, which is an area of ongoing debate.;

504 a| Includes bibliographical references.;

650 2 a| Fatty Acids, Omega-30| (DNLM)D015525=| ^A955841;

650 2 a| Diet0| (DNLM)D004032=| ^A918984;

650 2 a| Obesity0| (DNLM)D009765=| ^A917747;

650 2 a| Mitochondria0| (DNLM)D008928=| ^A917755;

650 2 a| Heart0| (DNLM)D006321=| ^A917646;

650 2 a| Cardiolipins0| (DNLM)D002308=| ^A1357051;

653 a| Diet-Induced Obesity;

653 a| N-3 Fatty Acids;

700 1 a| Shaikh, Saame Raza,e| degree supervisor.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Biochemistry and Molecular Biology.?| UNAUTHORIZED;

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

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/6507;

994 a| C0b| ERE;

096 a| QU 90;

596 a| 1 4;

998 a| 4814938;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4814938-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 2/1/2018x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4814938-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 2/1/2018x| ETDz| HERESOURCE;

The influence of diet-induced obesity and N-3 fatty acids on the cardiac mitochondrial phospholipidome and respiratory activity / by E. Madison Robison.

Author/creator	Robison, E. Madison author.
Other author	Shaikh, Saame Raza, degree supervisor.
Other author	East Carolina University. Department of Biochemistry and Molecular Biology.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2017.
Description	239 pages : illustrations (some color).
Supplemental Content	Access via ScholarShip
Subjects	Fatty Acids, Omega-3 Diet Obesity Mitochondria Heart Cardiolipins

Series	ECU Brody School of Medicine dissertation ECU Brody School of Medicine dissertation. UNAUTHORIZED
Summary	Cardiac mitochondrial phospholipids, notably cardiolipin (CL), regulate inner mitochondrial membrane (IMM) organization and protein function, particularly the enzymes associated with respiration. In a range of metabolic diseases, CL and other phospholipids undergo acyl chain remodeling, which would presumably impair respiratory activity. In diet-induced obesity, the influence of cardiac remodeling on respiratory enzyme activity and mitochondrial respiration is poorly studied. Thus, we first established the effect of diet-induced obesity on the mitochondrial phospholipidome and subsequent influences on mitochondrial function using two different dietary models. Surprisingly, the high fat diet and western diet remodeled the phospholipidome, but both obesogenic diets had no influence on cardiac mitochondrial supercomplex formation, respiratory enzyme activities, or respiration. Therefore, we next investigated how extremely remodeling with dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) in the context of obesity, would influence the mitochondrial phospholipidome and thereby respiration. The rationale for focusing on n-3 PUFAs was that these fatty acids are generally considered cardioprotective but paradoxically are elevated in several metabolic diseases. Dietary supplementation with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) extensively remodeled the phospholipidome. Particularly, CL acyl chains were remodeled to include DHA at the loss of linoleic acid, which is incorporated into 90% of CL species. Strikingly, supplementation with DHA reduced the activities of several respiratory enzymes, although overall respiration was not affected. We tested the hypothesis that the reduction in enzymatic activity with DHA was driven by the replacement of linoleic acid with DHA in CL species. Indeed, fusion of linoleic acid to mitochondria isolated from DHA-fed mice, rescued the impairments in the CL lipidome and thereby several respiratory complex activities. These results suggest that increased DHA in the myocardium in differing diseases may be targeting enzymatic activity. Taken together, the data establish that obesity by itself in mice does not disrupt respiratory enzyme activity despite remodeling of CL acyl chains. However, extensive remodeling with n-3 PUFAs has a strong influence. Finally, this study has implications for future nutritional studies on the balance between linoleic acid and n-3 PUFAs in the heart, which is an area of ongoing debate.
General note	Presented to the faculty of the Department of Biochemistry and Molecular Biology
General note	Advisor: Saame R. Shaikh
General note	Title from PDF t.p. (viewed February 22, 2018).
Dissertation note	Ph.D. East Carolina University 2017.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Availability

Library	Location	Call Number	Status	Item Actions
	Electronic Resources	Access Content Online	✔ Available

The influence of diet-induced obesity and N-3 fatty acids on the cardiac mitochondrial phospholipidome and respiratory activity / by E. Madison Robison.

Click here for more information about this title

Availability