Increased fat oxidation in 3T3-L1 adipocytes through forced expression of UCP 1

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dc.contributor.advisorJayaraman, Arul
dc.contributor.committeeMemberHahn, Juergen
dc.contributor.committeeMemberHarris, Edward
dc.contributor.committeeMemberMuthuchamy, Mariappan
dc.creatorPalani, Santhosh
dc.date.accessioned2006-10-30T23:25:09Z
dc.date.available2006-10-30T23:25:09Z
dc.date.created2005-08
dc.date.issued2006-10-30
dc.description.abstractObesity is a chronic condition that primarily develops from an increase in body fat in the form of white adipose tissue (WAT) mass. The resulting adiposity is a risk factor for many diseases, including type 2 diabetes (T2D), cardiovascular diseases, and some forms of cancer. Reducing WAT mass by targeted modulation of metabolic enzymes in fat cell metabolism is an attractive molecular therapeutic alternative to dietary approaches. In the present study, we exogenously up-regulate a novel respiratory uncoupling protein to increase substrate oxidation, and thereby control adipocyte fatty acid content. Increasing molecular evidence points to a family of uncoupling proteins (UCPs) playing an important role in adipocyte fat metabolism. Of specific interest is UCP1, which in brown adipocytes mediates energy dissipation as heat by de-coupling respiration and ATP synthesis. UCP1 is minimally expressed in white adipose tissue (WAT). We hypothesize that controlled expression of UCP1 in WAT will result in enhanced fatty acid oxidation to compensate for reduced ATP synthesis. We used a Tet-Off retroviral transfection system to express UCP1, with doxycycline being used to control the extent of expression. UCP1 cDNA was cloned into pRevTRE and was stably transfected into 3T3-L1 preadipocytes prior to differentiating them into adipocytes. A reporter gene (EGFP) was also transfected in parallel to optimize the transfection and preadipocyte differentiation conditions as well as to demonstrate regulated expression. Metabolite measurements showed that the UCP1-expressing adipocytes accumulated 83% less triglyceride and 85 % free fatty acids while maintaining constant ATP levels. These results suggest UCP1 and other metabolic enzymes as potential targets for development of pharmacological agents for the treatment of obesity and related disorders.en
dc.format.digitalOriginborn digitalen
dc.format.extent4408128 bytesen
dc.format.mediumelectronicen
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/1969.1/4207
dc.language.isoen_US
dc.publisherTexas A&M University
dc.subjectFat Oxidationen
dc.subjectUCP1en
dc.subjectadipocytesen
dc.titleIncreased fat oxidation in 3T3-L1 adipocytes through forced expression of UCP 1en
dc.typeBooken
dc.typeThesisen
dc.type.genreElectronic Thesisen
dc.type.materialtexten
thesis.degree.departmentChemical Engineeringen
thesis.degree.disciplineChemical Engineeringen
thesis.degree.grantorTexas A&M Universityen
thesis.degree.levelMastersen
thesis.degree.nameMaster of Scienceen

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