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Fat and fit: metabolic changes in skeletal muscle of liver fatty acid-binding protein knockout mice

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Title
Fat and fit: metabolic changes in skeletal muscle of liver fatty acid-binding protein knockout mice
Name (type = personal)
NamePart (type = family)
Xu
NamePart (type = given)
Heli
NamePart (type = date)
1991-
DisplayForm
Heli Xu
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Storch
NamePart (type = given)
Judith
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Judith Storch
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Watford
NamePart (type = given)
Malcolm
DisplayForm
Malcolm Watford
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Anthony
NamePart (type = given)
Tracy G.
DisplayForm
Tracy G. Anthony
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Henderson
NamePart (type = given)
Greg
DisplayForm
Greg Henderson
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
School of Graduate Studies
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2019
DateOther (encoding = w3cdtf); (qualifier = exact); (type = degree)
2019-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2019
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
Abstract
Liver fatty acid-binding protein (LFABP, FABP1) is abundantly expressed in the liver and small intestine, and thought to facilitate hepatic and intestinal lipid trafficking into various metabolic pathways with its high binding affinity for long chain fatty acids. Moreover, LFABP has also been implicated in regulating systemic energy homeostasis based on studies of LFABP null (LFABP-/-) mice. We and others have previously reported that LFABP-/- mice exhibit greater body weight gain and body fat mass in response to high fat feeding compared with wild-type (WT) mice. Despite being more obese, however, LFABP-/- mice were protected from high fat feeding-induced decline in exercise capacity, showing an approximate doubling of running distance compared with WT mice on the high fat diet. In studies aimed at understanding the metabolic changes in skeletal muscle underlying this surprising exercise phenotype in LFABP-/- mice, we found significantly higher triglyceride and glycogen content, as well as increased mitochondrial enzyme activities and fatty acid oxidation capacity in the resting muscles of LFABP-/- mice, suggesting a greater substrate storage and mitochondrial function at resting state. During a low intensity exercise, LFABP-/- mice showed a preference for carbohydrate utilization in the first 10 min of the exercise and switched to a higher lipid utilization compared with WT during the rest 10 min of exercise, with greater exercise-dependent decreases in muscle glycogen stores and elevated free fatty acid in the plasma after exercise. Using cellular bioenergetics measurements, primary myoblasts from high fat-fed LFABP-/- mice showed a higher respiratory capacity compared with WT mice, supporting the increased exercise capacity of LFABP-/- mice. Interestingly, primary myotubes from chow-fed mice treated with fatty acids only showed modest difference between the genotypes, suggesting that apart from a high concentration of plasma FAs, other circulating mediators may be required for the improved muscle energy metabolism in high fat fed-LFABP-/- mice. In examining potential interorgan signaling possibilities, we found similar insulin sensitivity in skeletal muscle between the genotypes, suggesting an insulin-independent mechanism mediating the muscle metabolic changes in LFABP-/- mice. Moreover, we found decreased FGF21 expression levels in the liver and trending lower FGF21 levels in the plasma of LFABP-/- mice, despite our previous report that LFABP-/- mice showed trending higher plasma levels of adiponectin, a downstream target of FGF21. However, we found similar FGF21 sensitivity in epidydimal adipose tissues between the genotypes and trending lower expression levels of adiponectin in the epidydimal adipose tissues, suggesting that FGF21-meidated adiponectin production and secretion may be enhanced in other fat depots. Overall, muscle metabolic reprogramming in LFABP-/- mice underlies their resistance to high fat feeding-induced decline in exercise capacity, including increased substrate availability and improved mitochondrial function in response to high fat diets. Since LFABP is not expressed in the muscle, these alterations in muscle energy metabolism of LFABP-/- mice appear to be induced signaling molecules in the plasma, possibly involving adiponectin.
Subject (authority = ETD-LCSH)
Topic
Fatty acids
Subject (authority = RUETD)
Topic
Nutritional Sciences
Subject (authority = ETD-LCSH)
Topic
Metabolism -- Regulation
Subject (authority = ETD-LCSH)
Topic
Obesity
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9640
PhysicalDescription
Form (authority = gmd)
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xii, 124 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Musculoskeletal system
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/t3-qm12-4y05
Genre (authority = ExL-Esploro)
ETD doctoral
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RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Xu
GivenName
Heli
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2019-03-31 15:57:30
AssociatedEntity
Name
Heli Xu
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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Author Agreement License
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
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Copyright protected
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Open
Reason
Permission or license
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ETD
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windows xp
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2019-06-17T20:50:51
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