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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 296/4/E802    most recent 90725.2008v1 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 Carmo, S. D. Articles by Rassart, E. Search for Related Content PubMed PubMed Citation Articles by Carmo, S. D. Articles by Rassart, E.

Human apolipoprotein D overexpression in transgenic mice induces insulin resistance and alters lipid metabolism

Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, and BioMed, Centre de Recherches Biomédicales, Université du Québec à Montréal, Montreal, Quebec, Canada

Submitted 28 August 2008 ; accepted in final form 10 January 2009

Apolipoprotein D (apoD), a widely expressed lipocalin, has the capacity to transport small hydrophobic molecules. Although it has been proposed that apoD may have multiple tissue-specific, physiological ligands and functions, these have yet to be identified. To gain insight in some of its functions, we generated transgenic mice overexpressing human apoD (H-apoD) under the control of neuron-specific promoters. In Thy-1/apoD and NSE/apoD mice, expression of H-apoD was strong in the nervous system although weakly detected in peripheral organs such as the liver and blood cells. These mice displayed not entirely anticipated metabolic defects. Although they are not obese and have normal lipid concentration in circulation, Thy-1/apoD and NSE/apoD mice are glucose intolerant, insulin resistant, and develop hepatic steatosis. The steatosis and its associated insulin resistance are correlated with impairments in hepatic lipogenesis. However, they are not strongly related with inflammation. This impaired insulin response is not caused by a decrease in circulating leptin or a modulation of adiponectin and resistin levels. These results suggest that variations in the levels and/or sites of apoD expression influence the lipid and glucose metabolism, consolidating apoD as a target for insulin-resistance-related disorders.

hepatic steatosis; inflammation; neuronal promoters