Semester

Spring

Date of Graduation

2013

Document Type

Thesis

Degree Type

PhD

College

Davis College of Agriculture, Natural Resources and Design

Department

Animal and Nutritional Sciences

Committee Chair

Kimberly M. Barnes

Committee Co-Chair

Kenneth P. Blemings

Committee Member

Lisa Salati

Committee Member

Matthew E. Wilson

Committee Member

Jianbo Yao

Abstract

Obesity is a main health concern and leads to many other health complications. Conjugated linoleic acid (CLA) has been shown to cause a reduction in obesity in several species. CLAinduced body fat loss is enhanced when mice are fed coconut oil (CO). The objectives were to determine if the CLA-induced lipolysis in different oil source-fed mice was time-dependent and to determine the effect of cell signaling inhibitors on CO+CLA-induced lipolysis. Study 1: Male mice (ICR; n=80; 3wk) were fed 7% soybean oil (SO) or CO diets for 6wk and then supplemented with 0 or 0.5% CLA for 3, 7, 10 or 14d. Body fat index (BFI) was calculated as [(epididymal fat pad + retroperitoneal fat pad)/ body weight] and lipolysis was determined by non-esterified fatty acid (NEFA) and glycerol release in 3hr ex vivo cultures. BFI was reduced by CO on d7 (P<0.01) and CLA tended (P=0.09) to decrease BFI in CO-fed mice on d10. BFI was reduced in both CO and SO-fed mice (P<0.05) in response to CLA on d14. NEFA release was increased by CLA in CO-fed mice (P<0.01) but not in SO-fed mice on d7 and 10 but on d14 CLA increased NEFA release in both CO and SO-fed mice (P<0.0001). Glycerol release was also increased by CLA in CO-fed mice but not in SO-fed mice on d3 and d7 (P<0.05). We then determined expression and activation level of proteins involved in lipolysis and lipogenesis. CLA tended to decrease (P=0.06) p-perilipin protein expression in CO-fed mice. There was also a trend for CLA (P=0.06) to decrease adipose triglyceride lipase (ATGL) protein. CO-fed mice had greater fatty acid synthase, stearoyl CoA desaturase 1 mRNA expression and less acetyl CoA carboxylase mRNA expression (P<0.01). Sterol regulatory binding protein 1c and malic enzyme expression was least in CO+CLA-fed mice. Study 2: 3T3-L1 cells were differentiated, exposed to CO or SO for 10d, serum starved overnight, and pre-loaded with 3[H]-oleic acid for 12 hrs. Cells were treated with 50 muM CLA or linoleic acid (LA) with/without cell signaling inhibitors for 12-24 hrs. Lipolysis was measured as the 3-hr release of 3[H]-oleic acid. Without inhibitors, CO+CLA treatment caused more lipolysis (P<0.01) than all other treatments, which did not differ. None of the inhibitors tested reduced lipolysis in CO+CLA treated cells. Cyclooxegenase-2 inhibitor increased lipolysis of SO+CLA treated cells (P=0.05) to the level of CO+CLA. Phospholipase C inhibitor increased lipolysis in all treatments (P<0.0001) except that of CO+CLA. Peroxisome proliferator-activated receptor alpha inhibitor also increased lipolysis of CO+LA (P<0.05) to the level of CO+CLA treated cells and in SO+CLA treated cells. There was no effect of the p42 mitogen-activated protein kinase or protein kinase A inhibitor, compared to absence of inhibitor. Therefore CLA-induced lipolysis occurs more rapidly in CO vs SO-fed mice and the CLA enhanced lipolysis in CO group could involve the PLC pathway.

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