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This version published online on May 12, 2005
Endocrinology, doi:10.1210/en.2005-0204
A more recent version of this article appeared on August 1, 2005
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Submitted on February 17, 2005
Accepted on May 2, 2005

The Spot 14 protein is required for de novo lipid synthesis in the lactating mammary gland

Qihong Zhu, Grant W. Anderson, Gregory T. Mucha, Elizabeth J. Parks, Jennifer K. Metkowski, and Cary N. Mariash*

Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, MN 55454; Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55108

* To whom correspondence should be addressed. E-mail: mariasc{at}umn.edu.

We generated a Spot 14 null mouse to assess the role of Spot 14 in de novo lipid synthesis and report the Spot 14 null mouse exhibits a phenotype in the lactating mammary gland. Spot 14 null pups nursed by Spot 14 null dams gain significantly less weight than wild-type pups nursed by wild-type dams. In contrast, Spot 14 null pups nursed by heterozygous dams show similar weight gain to wild-type litter-mates. We found the triglyceride content in Spot 14 null milk is significantly reduced. We demonstrate this reduction is the direct result of decreased de novo lipid synthesis in lactating mammary glands, corroborated by a marked reduction of medium chain fatty acids in the triglyceride pool. Importantly, the reduced lipogenic rate is not associated with significant changes in the activities or mRNA of key lipogenic enzymes. Finally, we report the expression of an S14-related (S14-R) gene in liver and adipose tissue, which is absent in the lactating mammary gland. We suggest that expression of both the S14 and S14-R proteins is required for maximum efficiency of de novo lipid synthesis in vivo and these proteins impart a novel mechanism regulating de novo lipogenesis.
Key words: lipogenesis • Spot 14 • mammary gland • knockout mouse




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