Document Detail


Lipid synthesis in lactation: diet and the fatty acid switch.
MedLine Citation:
PMID:  18027074     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The lipid component of milk provides the critical nutritional source for generating both energy and essential nutrients to the growth of the newborn. Three types of substrate are utilized to synthesize milk triacylglycerides (TAG): dietary fat, fatty acids mobilized from adipose tissue stores, and lipids synthesized de novo synthesis from glucose and other dietary precursors, a process often referred to as de novo lipogenesis. The utilization of these various sources for TAG synthesis by the mammary epithelial cells is influenced by both the stage of lactation and the diet. From studies of gene expression in FVB mice, we observed that genes for beta-oxidation of fatty acids are downregulated along with the expression of Acyl-CoA thioesterase 1 (ACOT1). As a control mechanism we propose that during pregnancy ACOT1 provides a supply of cytoplasmic free fatty acids which increase the activation of PPARgamma. Ligand-induced activation of the PPAR/RXR transcription factor complex by free fatty acids, upregulates expression of genes required for beta-oxidation of fatty acids. The fall in ACOTs at secretory activation may facilitate the switch to lipogenesis perhaps mediated by activation of the LXR/RXR transcription factor complex. The response to changes in the supply of dietary lipids, on the other hand, is likely to be mediated by SREBP1, possibly acting through modulation of Spot 14. Stability of SREBP1 may be enhanced by a significant increase in Akt at secretory activation. These regulatory pathways may be critical to the production of milk with a balanced TAG composition to support neonatal development of the newborn.
Authors:
Michael C Rudolph; Margaret C Neville; Steven M Anderson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-20
Journal Detail:
Title:  Journal of mammary gland biology and neoplasia     Volume:  12     ISSN:  1083-3021     ISO Abbreviation:  J Mammary Gland Biol Neoplasia     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-28     Completed Date:  2008-02-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9601804     Medline TA:  J Mammary Gland Biol Neoplasia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  269-81     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Colorado Health Sciences Center, Anschutz Medical Campus, 12801 East 17th Avenue, Mail Stop 8104, P.O. Box 6511, Aurora, CO 80045, USA.
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MeSH Terms
Descriptor/Qualifier:
Animal Feed
Animals
Diet
Fatty Acids / metabolism*
Gene Expression Regulation
Humans
Lactation / metabolism*
Lipids / biosynthesis*
Mammary Glands, Animal / metabolism
Mammary Glands, Human / metabolism
Grant Support
ID/Acronym/Agency:
P01-HD38129/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Lipids

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