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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/C1543    most recent 00371.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Collison, L. W. Articles by Jolly, C. A. Search for Related Content PubMed PubMed Citation Articles by Collison, L. W. Articles by Jolly, C. A.

GROWTH, DIFFERENTIATION, AND APOPTOSIS

Glycerol-3-phosphate acyltransferase-1 regulates murine T-lymphocyte proliferation and cytokine production

¹Division of Nutritional Sciences, Department of Human Ecology, The University of Texas at Austin, Austin, Texas; and ²Department of Physiology and Pharmacology, The University of North Dakota, Grand Forks, North Dakota

Submitted 17 August 2007 ; accepted in final form 23 October 2008

We have previously established a correlation between reduced mitochondrial glycerol-3-phosphate acyltransferase-1 (GPAT-1) activity and decreased proliferation in splenic T-lymphocytes from aged rats. To better understand the immunoregulatory role of GPAT-1, we examined T-lymphocyte function in young GPAT-1 knockout (KO) mice. We show that without GPAT-1, T-lymphocyte proliferation is inhibited and activation induced apoptosis is increased. Th-1 (IL-2 and IFN-) cytokine secretion is reduced, and Th-2 (IL-4 and IL-10) cytokine secretion is increased. These changes may be due to alterations in membrane lipid composition since we found changes in the relative content of individual phospholipid species. Furthermore, we show increased arachidonate content and subsequent increased prostaglandin E₂ secretion, which may inhibit T-lymphocyte proliferation. Taken together, we show a novel link between GPAT-1 and changes in T-lymphocyte function. These data have broad health implications because GPAT-1 suppression has recently been implicated as a new target for preventing insulin sensitivity and hepatic steatosis and we show that immune function may also be affected. Interestingly, the changes in young GPAT-1 KO splenic T-lymphocytes are similar to defects commonly seen in T-lymphocytes from aged rodents, which further underscores the significance of GPAT-1 in T-lymphocyte function.

lipid mediators; cell proliferation; spleen and lymph nodes