Nakamura - ARTICLE Increased Hepatic A6-Desaturase Activity...

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ARTICLE Increased Hepatic A6-Desaturase Activity with Growth Hormone Expression in the MG101 Transgenic Mouse 1 Manabu T. Nakamura a,2, Stephen D. Phinney b'*, Anna B. Tang b, Anita M. Oberbauer c, J. Bruce German a, and James D. Murray c Departments of CAnimal Science, aFood Science & Technology, blnternal Medicine, and Cpopulation Health and Reproduction, University of California, Davis, California ABSTRACT: Growth hormone (GH) has many metabolic ef- fects, but its mechanism(s) of action are not fully understood. We studied the short-term effects of endogenously produced GH on liver A6-desaturase activity and adipose and liver lipid fraction fatty acid composition in transgenic mice. MG101 transgenic mice ages 73-114 d received zinc to activate the ovine GH transgene for 7 d. Nontransgenic littermates, used as controls, also received zinc. Liver lipids were fractionated into phospholipids (PL), cholesteryl esters, and triglycerides (TG), and retroperitoneal adipose fractionated into PL and TG for fatty acid analysis. Liver microsomes were assayed for A6-desaturase activity. Animals expressing the ovine growth hormone trans- gene had a 2.5-fold higher liver A6-desaturase activity than con- trols. Arachidonate and docosahexaenoate were significantly higher in liver PL of GH transgenic animals compared to con- trois, but both were decreased in adipose PL in the GH animals. We conclude that increased production of GH affects both pro- duction and organ distribution of highly unsaturated fatty acids. The changes in arachidonate in various lipid pools following transgene expression may mediate the systemic actions of GH. Lipids31, 139-143 (1996). Transgenic animals carrying growth hormone (GH) genes can have increased lean body mass and growth, which is of po- tential benefit to meat production. However, most of these transgenic animal lines suffer from various side effects in- cluding arthritis and impaired immune and reproductive func- tions (1). The MG101 mouse carries the ovine GH (oGH) structural gene fused with the sheep metallothionein la (oMTla) promoter (2). With this combination, the MG101 mice have a minimal level of basal expression of oGH, but high expression induced with 25 mM zinc in their drinking water (2). This strain of mice does not show apparent pathol- IThis paper is dedicated to Dr. John E. Kinsella, who died on May 2, 1993. 2present address: Department of Human Ecology, GEA 115, University of Texas, Austin, TX 78712. *To whom correspondence should be addressed at Division of Clinical Nu- trition TB-156, University of California, Davis, CA 95616. Abbreviations: CE, cholesteryl esters; GH, growth hormone; oMTla, ovine metallothionein la; oGH, ovine growth hormone; PL, phospholipids; TG, triglycerides. ogy after prolonged induction of GH. Nevertheless, these mice show marked enlargement of the liver and spleen (3) in addition to increased overall body size. Recent studies suggest that GH stimulates hematopoiesis and modulates immune functions, although the mechanisms of these effects are unknown (4). Maddaiah and Clejan (5) re- ported that GH administration to hypophysectomized rats
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Nakamura - ARTICLE Increased Hepatic A6-Desaturase Activity...

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