Progress 09/15/01 to 09/30/04
Outputs
Leptin is produced by adipocytes (fat cells), and may act locally to limit how much fat is stored in these cells. Our findings to date indicate that leptin acts on pig adipocytes to stimulate lipolysis, the process by which fat is removed from adipocytes for utilization in other tissues. However, the lipolytic effect of leptin is achieved with no change in inhibitory G-protein function or abundance in the adipocyte. In another aspect of this work, we have determined that the ability of adipocytes to produce fat from glucose via lipogenesis is marginally reduced by leptin in vitro, but that adipocytes isolated from pigs treated with leptin, in vivo, are actually predisposed to respond to leptin in vitro with a marginal increase in lipogenic activity. We are currently establishing whether auto-regulation of the leptin receptor, in vivo or in vitro, impacts the sensitivity of the adipocyte to leptin or insulin. We hypothesized that chronic leptin exposure would down
regulate the leptin receptor, and that this would attenuate the anti-lipogenic activity of leptin and thus promote insulin-stimulated lipogenesis. Thus far, we have seen no indications that leptin administration causes a down regulation of leptin receptor expression in adipocytes. The results of our work provide essential information that will allow us to target signaling pathways within the adipocyte to gain greater control of how pigs partition dietary energy, and thus improve feed efficiency and producer profitability.
Impacts
The results of our work provide essential information that will allow us to target specific tissues and signaling pathways within particular cell types to further establish the role of the adipocyte in the regulation of energy balance, and as a participant in the immune response. It is through these discoveries that novel strategies to improve the efficiency of animal production, and address animal well-being issues, will be developed.
Publications
- Wulster-Radcliffe, M. C., J. A. Christian, J. Wang, and M. E. Spurlock. 2004. The anti-inflammatory actions of adiponectin include the regulation of IL-6 and IL-10, and a suppression of cell proliferation that is associated with increased caspase activity. Biochem. Biophys. Res. Comm.316(3):924-929
- Ajuwon, K.M, S.K. Jacobi, J.L. Kuske, and M.E. Spurlock. 2004. Primary pig adipocytes respond directly to lipopolysaccharide and interferon-f by increasing the expression of interleukin-6 andinterleukin-15. Am J Physiol. 286(3):R547-53
- Jacobi, S., K.M. Ajuwon, T.E. Weber, J.L. Kuske, C.J. Dyer, and M.E. Spurlock. 2004. Cloning and Expression of Porcine Adiponectin, and its Relationship to Adiposity, Lipogenesis, and the Acute Phase Response. J. Endocrinol. 182(1):133-44.
- Weber, T. E., and M. E. Spurlock. 2004. Leptin alters antibody isotype in the pig in vivo, and prevents dexamethasone-induced down-regulation of the anti-apoptotic gene, bcl-xL, in peripheral blood monocytes in vitro. 2004. J. Anim. Sci. 82(6):1630-40.
- Ajuwon, K. M., and M. E. Spurlock. 2004. Direct Regulation of Lipolysis and Lipogenesis by Interleukin-15 in Primary Pig Adipocytes. Am. J. Physiol.287(3):R608-11.
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Progress 10/01/02 to 09/30/03
Outputs
Leptin and adiponectin are adipocyte-derived hormones, and individually and collectively, they coordinate multiple biochemical pathways that regulate energy metabolism and immune response axes. Our recent findings provide solid evidence (1) the pig adipocyte does indeed participate in the innate immune response, and (2) that adiponectin regulates this response, not only in adipocytes, but also in typical immune cells such as the monocyte and macrophage. Specifically, we have found that pig adipocytes respond directly to bacterial cell membrane antigens and interferon-gamma by producing pro-inflammatory cytokines. We have also found that adiponectin attenuates inflammation, and also stimulates programmed cell death in certain immune cells. In contrast with these results, we have found that adiponectin acts as a pro-inflammatory signal in a muscle cell model. These findings are particularly exciting given that the success of our genetic efforts to reduce adiposity in
commercial pigs over the past two decades has been accompanied by the emergence of genetic lines that are less tolerant of some disease challenges.
Impacts
The results of our work provide essential information that will allow us to target specific tissues and signaling pathways within particular cell types to further establish the role of the adipocyte in the regulation of energy balance, and as a participant in the immune response. It is through these discoveries that novel strategies to improve the efficiency of animal production, and address animal well-being issues, will be developed.
Publications
- Ajuwon, K.M., J.L. Kuske, D.M. Ragland, L. Adeola, D.L. Hancock, D.B. Anderson, and M.E. Spurlock. 2003. The regulation of IGF-1 by leptin in the pig is tissue specific and independent of changes in growth hormone. J. Nutr. Biochem. 14(9):522-530.
- Houseknecht, K.L., and M.E. Spurlock. 2003. The regulation of lipid metabolism in peripheral tissues by leptin. Invited Review, Nutrition Reviews International 16:83-96.
- Mills S.E., M.E. Spurlock, and D.J. Smith. 2003. Beta-adrenergic receptor subtypes that mediate ractopamine stimulation of lipolysis. J Anim Sci 81(3):662-8.
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Progress 10/01/01 to 09/30/02
Outputs
Leptin is produced by adipocytes (fat cells), and may act locally to limit how much fat is stored in these cells. Our findings to date indicate that leptin acts on pig adipocytes to stimulate lipolysis, the process by which fat is removed from adipocytes for utilization in other tissues. We have also found that the ability of adipocytes to produce fat via lipogenesis is reduced by leptin, and that both the lipolytic and anti-lipogenic actions of leptin are independent of the inhibitory G-protein functionality. However, leptin may interfere with the ability of adenosine to suppress lipolysis.
Impacts
The results of our work provide essential information that will allow us to target specific tissues and signaling pathways within the adipocyte to gain greater control of how pigs use dietary energy, and thus improve feed efficiency and producer profitability.
Publications
- No publications reported this period
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