High-Fat Diet Enhances Triglyceride Recycling, Impairs UCP1-Mediated Thermogenic Activity, and Causes Insulin Resistance in Rat Brown Adipocytes

Simple item page
dc.contributor.advisorCeddia, Rolando
dc.contributor.authorDa Eira, Daniel Pereira
dc.date.accessioned2019-11-22T18:41:23Z
dc.date.available2019-11-22T18:41:23Z
dc.date.copyright2019-06
dc.date.issued2019-11-22
dc.date.updated2019-11-22T18:41:23Z
dc.degree.disciplineKinesiology & Health Science
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractBrown adipose tissue (BAT) is rich in uncoupling protein 1 (UCP1) and dissipates energy through thermogenesis. However, even though BAT mass and its UCP1 content increase under conditions of diet-induced obesity (DIO), marked expansion of the WAT is not prevented, suggesting impairment of BAT-mediated diet-induced thermogenesis (DIT) in obesity. Thus, the objective of this study was to investigate the metabolic and molecular mechanisms that regulated BAT thermogenesis in DIO. To accomplish this, rats were fed a high-fat diet (HFD) for eight weeks. Subsequently, glucose and fat metabolism and the molecular mechanisms underlying these processes were assessed in BAT adipocytes. Despite increasing BAT mass (1.3-fold), UCP1 content (2.1-fold), and isoproterenol (Iso)-induced lipolysis (1.6-fold), HFD reduced UCP1-mediated glucose (62%) and fatty acid (57%) oxidation, and abrogated insulin-stimulated glucose uptake in BAT adipocytes. Furthermore, phosphoenolpyruvate carboxykinase (PEPCK) and glycerol kinase (GyK) contents, as well as glycerol and palmitate incorporation into lipids were all significantly increased (1.8-fold, 2.1-fold, 2-fold, and 1.7-fold, respectively) in HFD BAT. This coincided with 3.6- and 3.7-fold elevations in lipoprotein lipase (LPL) and cluster of differentiation 36 (CD36), respectively, in HFD BAT adipocytes. Morphological analysis also revealed that these adipocytes were more unilocular in appearance. Altogether, these findings provide novel evidence that HFD suppresses UCP1-mediated thermogenesis, shifts metabolism toward triglyceride recycling, and induces insulin resistance in BAT adipocytes. These adaptive responses to chronic HFD are consistent with a mechanism that attenuates the contribution of BAT to DIT and favors the growth of adipose tissue and the development of obesity. Thus reversal of these adaptive metabolic responses of brown adipocytes to DIO could be of therapeutic value for obesity and its related metabolic disorders.
dc.identifier.urihttp://hdl.handle.net/10315/36694
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectKinesiology
dc.subject.keywordsDiet-induced thermogenesis
dc.subject.keywordsobesity
dc.subject.keywordsmitochondria
dc.subject.keywordsglucose oxidation
dc.subject.keywordsmetabolism
dc.titleHigh-Fat Diet Enhances Triglyceride Recycling, Impairs UCP1-Mediated Thermogenic Activity, and Causes Insulin Resistance in Rat Brown Adipocytes
dc.typeElectronic Thesis or Dissertation

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
DaEira_Daniel_P_2019_Masters.pdf
Size:
1.8 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
license.txt
Size:
1.87 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
YorkU_ETDlicense.txt
Size:
3.39 KB
Format:
Plain Text
Description:
Download

Collections

Kinesiology & Health Science

All items in the YorkSpace institutional repository are protected by copyright, with all rights reserved except where explicitly noted.