The Spot 14 protein is required for de novo lipid synthesis in the lactating mammary gland.
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 littermates. 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 a Spot 14-related gene in liver and adipose tissue, which is absent in the lactating mammary gland. We suggest that expression of both the Spot 14 and Spot 14-related proteins is required for maximum efficiency of de novo lipid synthesis in vivo and that these proteins impart a novel mechanism regulating de novo lipogenesis.
Zhu
Qihong
Q
Division of Endocrinology and Diabetes, Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Anderson
Grant W
GW
Mucha
Gregory T
GT
Parks
Elizabeth J
EJ
Metkowski
Jennifer K
JK
Mariash
Cary N
CN
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D007774:Lactation / Q000502:physiology*; D008055:Lipids / Q000096:biosynthesis*; D008321:Mammary Glands, Animal / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000737:chemistry; D008894:Milk Proteins / Q000032:analysis; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
D008055:Lipids; D008894:Milk Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; C051065:THRSP protein, human; C501477:Thrsp protein, mouse; D014157:Transcription Factors; D000103:Acetyl-CoA Carboxylase