Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/95364
Type: Thesis
Title: The effect of dietary fatty acid composition on skeletal muscle and hepatic fatty acid and glucose metabolism in male and female mice.
Author: Philp, Lisa Kate
Issue Date: 2011
School/Discipline: School of Medicine
Abstract: Australian adults consume ~6% above the recommended intake of saturated fat and less than half the recommended daily amount of n-3 polyunsaturated fatty acids (PUFA). There is some evidence that the type and proportion of dietary fat consumed may influence the development of the obese phenotype and associated metabolic complications. Epidemiological studies indicate that a saturated fat-rich diet (HF-S) is deleterious, whilst consuming n-3 PUFAs is beneficial to metabolic health. Saturated fats have a greater propensity to enter storage in adipose tissue and ectopic stores, as opposed to being oxidised. This is deleterious as ectopic fat deposition in skeletal muscle and liver are strongly associated with insulin resistance. In contrast, diets rich in n-3 PUFA limit adipose tissue hypertrophy, reduce ectopic fat and prevent high fat diet (HFD)-induced insulin resistance in rats. However, the mechanism by which n-3 PUFA enrichment of a HF-S diet (HF-n-3) prevents ectopic fat deposition in muscle and liver is unclear; though pathways of fatty acid uptake, storage and oxidation may be implicated. Furthermore, in skeletal muscle a functional shift in fibre type may be implicated, as increased muscle n-3 PUFA content is associated with an increased proportion of oxidative fibres. The studies in this thesis therefore aimed to determine: (I) the effect of HFD fatty acid composition on metabolic profile, adipose tissue distribution, and muscle fibre type composition of male and female mice; (II) if HF-n-3 feeding influenced the mRNA content of 27 key genes that regulate the uptake (FAT/CD36, FABPpm, FATP), synthesis and storage (SREBF, INSIG, SCD, ACC, DGAT, HSL) and utilisation (PDK, PPAR, PGC1, AMPK, ACC, CPT1, UCP) of fatty acids and metabolism of glucose (HK, PFK, GYS) in the glycolytic extensor digitorum longus muscle, oxidative soleus muscle and liver of male and female mice. To assess these aims mice were fed either a control diet (16% energy from fat) or one of two HFDs (60% energy from fat), a HF-S or HF-n-3 (7.5% saturated fat replaced with n-3 PUFA) diet. I investigated the hypothesis that HF-n-3 feeding prevents ectopic fat deposition through enhanced uptake and utilisation, and reduced storage, of fatty acids. Despite similarly increased body weight with both HFDs, mesenteric fat mass decreased and brown fat increased with HF-n-3 feeding compared to HF-S feeding. HF-S feeding increased muscle and liver fat content; this was ameliorated by HF-n-3. As hypothesised, HF-n-3 feeding may ameliorate intramyocellular and intrahepatic fat accumulation through an altered pattern of fatty acid metabolism gene expression in those tissues, specifically through the concurrent activation of pathways regulating fatty acid transport and utilisation, whilst limiting pathways that promote fatty acid storage and lipogenesis. Muscle fibre type composition was unchanged with diet, although HF-n-3 feeding increased muscle oxidative capacity. HF-S mice exhibited increased plasma insulin and glucose metabolism was influenced by HF-n-3 feeding in a tissue-specific manner. These studies highlight the importance of gender and in skeletal muscle, muscle fibre type, to the overall characteristics, profile of gene expression and ultimate function of the skeletal muscle and liver.
Advisor: Wittert, Gary Allen
Mayrhofer, Graham
Janovska, Alena
Heilbronn, Leonie Kaye
Dissertation Note: Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2011
Keywords: high fat diet; saturated fat; N-3 polyunsaturated fatty acids; skeletal muscle; liver; fatty acid metabolism; glucose metabolism
Provenance: This electronic version is made publicly available by the University of Adelaide in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. This thesis may incorporate third party material which has been used by the author pursuant to Fair Dealing exceptions. If you are the owner of any included third party copyright material you wish to be removed from this electronic version, please complete the take down form located at: http://www.adelaide.edu.au/legals
Appears in Collections:Research Theses

Files in This Item:
File Description SizeFormat 
01front.pdf449.57 kBAdobe PDFView/Open
02whole.pdf9.06 MBAdobe PDFView/Open
PermissionsLibrary staff access only349.55 kBAdobe PDFView/Open
RestrictedLibrary staff access only10.13 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.