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Lipid Synthesis in Lactation: Diet and the Fatty Acid Switch

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Abstract

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 β-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 PPARγ. Ligand-induced activation of the PPAR/RXR transcription factor complex by free fatty acids, upregulates expression of genes required for β-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.

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Abbreviations

ACBP:

acyl-CoA binding protein

ACOT:

acyl-CoA thioesterase

ADRP:

adipocyte differentiation regulated protein or adipophillin

AGPAT:

acyl-glycerol-3-phosphate-acyl transferase

ATP:

adenosine triphosphosphate

ER:

endoplasmic reticulum

ELOVL:

elongation of very long chain fatty acids

FABP:

fatty acid binding protein

FABP-FA:

fatty acid bound fatty acid binding protein

FAD:

Δ5-fatty acid desaturase

FASN:

fatty acid synthase

FFA:

free fatty acid

GK:

glycerol kinase

GPAT:

glycerol-3-phosphate acyltransferase

HSL:

hormone sensitive lipase

INSIG:

insulin induced gene

L2:

day 2 of lactation

L9:

day 9 of lactation

LACS:

long chain acyl-CoA synthase

LC-PUFA:

long chain polyunsaturated fatty acid

LPL:

lipoprotein lipase

LXR:

liver X receptor

MAG:

monoacylglycerol

MCFA:

medium chain fatty acid

mTOR:

mammalian target of Rapamycin

MUFA:

monounsaturated fatty acid

P17:

day 17 of pregnancy

n-SREBP:

nuclear sterol response element binding protein

PPAR:

peroxidase proliferators-activated receptor

PPRE:

PPAR response element

PUFA:

polyunsaturated fatty acid

RXR:

retinoic X receptor

S14:

Spot 14

SCAP:

SREBP cleavage activating protein

SCD:

stearoyl-coenzyme A desaturase

SREBP:

sterol response element binding protein

TAG:

triacyl glycerol

VLDL:

very low density lipoprotein

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Acknowledgements

We especially thank Dr. Yamada, Department of Clinical Biochemistry at Tokyo University of Pharmacy and Life Sciences, for kindly providing reagents and for his informative correspondence. We also acknowledge Lisa Litzenberger for her assistance with the figures presented in this review. The authors would also like to thank the members of the Mammary Gland Biology Program Project Grant at the University of Colorado Health Sciences Center for discussions and sharing of ideas. Research in our labs (MCN and SMA) is supported by PO1-HD38129.

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Authors and Affiliations

  1. Departments 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

    Michael C. Rudolph & Steven M. Anderson

  2. Program in Molecular Biology, University of Colorado Health Sciences Center, Anschutz Medical Campus, 12801 East 17th Avenue, Mail Stop 8104, P.O. Box 6511, Aurora, CO, 80045, USA

    Michael C. Rudolph & Steven M. Anderson

  3. Departments of Physiology and Biophysics, University of Colorado Health Sciences Center, Anschutz Medical Campus, 12801 East 17th Avenue, Mail Stop 8104, P.O. Box 6511, Aurora, CO, 80045, USA

    Margaret C. Neville

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  1. Michael C. Rudolph
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Correspondence to Steven M. Anderson.

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Rudolph, M.C., Neville, M.C. & Anderson, S.M. Lipid Synthesis in Lactation: Diet and the Fatty Acid Switch. J Mammary Gland Biol Neoplasia 12, 269–281 (2007). https://doi.org/10.1007/s10911-007-9061-5

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  • DOI: https://doi.org/10.1007/s10911-007-9061-5

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