Maternal obesity reduces milk lipid production in lactating mice by inhibiting acetyl-CoA carboxylase and impairing fatty acid synthesis.
Maternal metabolic and nutrient trafficking adaptations to lactation differ among lean and obese mice fed a high fat (HF) diet. Obesity is thought to impair milk lipid production, in part, by decreasing trafficking of dietary and de novo synthesized lipids to the mammary gland. Here, we report that de novo lipogenesis regulatory mechanisms are disrupted in mammary glands of lactating HF-fed obese (HF-Ob) mice. HF feeding decreased the total levels of acetyl-CoA carboxylase-1 (ACC), and this effect was exacerbated in obese mice. The relative levels of phosphorylated (inactive) ACC, were elevated in the epithelium, and decreased in the adipose stroma, of mammary tissue from HF-Ob mice compared to those of HF-fed lean (HF-Ln) mice. Mammary gland levels of AMP-activated protein kinase (AMPK), which catalyzes formation of inactive ACC, were also selectively elevated in mammary glands of HF-Ob relative to HF-Ln dams or to low fat fed dams. These responses correlated with evidence of increased lipid retention in mammary adipose, and decreased lipid levels in mammary epithelial cells, of HF-Ob dams. Collectively, our data suggests that maternal obesity impairs milk lipid production, in part, by disrupting the balance of de novo lipid synthesis in the epithelial and adipose stromal compartments of mammary tissue through processes that appear to be related to increased mammary gland AMPK activity, ACC inhibition, and decreased fatty acid synthesis.
Division of Basic Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Graduate Program in Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Jessica L
JL
Saben
Division of Basic Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Elise S
ES
Bales
Center for Human Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Matthew R
MR
Jackman
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
David
D
Orlicky
Center for Human Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
Paul S
PS
MacLean
Division of Basic Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Graduate Program in Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Center for Human Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America; Department of Physiology and Biophysics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.
James L
JL
McManaman
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D007774:Lactation / Q000187:drug effects; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk / Q000378:metabolism*; D009035:Mothers; D009765:Obesity / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*
D005227:Fatty Acids; D064429:Fatty Acid Synthases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase