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The metabolic and molecular regulation of adipose triglyceride lipase

Deiuliis, Jeffrey A.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1185546165

Abstract Details

2007, Doctor of Philosophy, Ohio State University, Ohio State University Nutrition.
Adipose triglyceride lipase (ATGL) is a newly identified lipase that initiates triglyceride lipolysis. We characterized expression of ATGL in pig, cattle, and mice. In pig, we concentrated on hormonal and dietary regulation of ATGL expression. In cow, we examined whether ATGL transcription was upregulated by the increased energy requirements of early lactation. We cloned porcine and bovine ATGL genes and designed and validated real-time PCR primer sets. ATGL gene expression increases dramatically in subcutaneous adipose during development and maturation, as well as during in vitro adipogenesis. Treatment of differentiated primary pig preadipocytes with insulin, epinephrine and forskolin decreased ATGL gene expression, suggesting that PI3K and PKA signaling decrease ATGL gene expression. ATGL gene and protein levels were increased in perirenal and subcutaneous fat depots by two weeks of calorie restriction in gilts. We continued our research on the metabolic regulation of ATGL in brown adipose tissue (BAT) of mice as well as whole BAT lipid metabolism. BAT is a unique fat depot in mammals for oxidation of dietary fuel substrates without production of chemical energy. Pharmaceutical-induced nonshivering thermogenesis in BAT results in the prevention and treatment of obesity in rodents and shows promise in humans. Cold exposure led to a decrease in ATGL protein and gene expression in mouse BAT. To investigate how cold exposure-induced signaling affects ATGL expression, the beta3-adrenergic receptor agonist CL 316,243 was used. CL 316,243 potently activated PI3K/Akt, ERK 1/2, and p38 ex vivo and in cultures of primary brown adipocytes and results in rapid and significant decreases in ATGL and adipose fatty acid binding protein. CL 316,243 induced increased lipolysis, despite decreased ATGL protein. Our data suggest that ATGL is degraded by PKA signaling. However, the proteasome inhibitor MG 132 failed to rescue CL-mediated degradation, suggesting non-proteasomal degradation of ATGL via beta3-adrenergic signaling. Inhibition of CL 316,243-mediated PI3K/Akt signaling by LY294002, ERK 1/2 signaling by PD-98059, and p38 signaling by SB 203580, failed to rescue ATGL protein degradation. However, inhibition of PKA by H89, fully rescued ATGL gene and protein levels at 1 and 3 hours, further suggesting that ATGL is targeted by PKA signaling.
Kichoon Lee (Advisor)
174 p.

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Citations

  • Deiuliis, J. A. (2007). The metabolic and molecular regulation of adipose triglyceride lipase [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1185546165

    APA Style (7th edition)

  • Deiuliis, Jeffrey. The metabolic and molecular regulation of adipose triglyceride lipase. 2007. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1185546165.

    MLA Style (8th edition)

  • Deiuliis, Jeffrey. "The metabolic and molecular regulation of adipose triglyceride lipase." Doctoral dissertation, Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=osu1185546165

    Chicago Manual of Style (17th edition)

osu1185546165
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© 2007, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.