Abstract
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.
Highlights
Nutrition during fetal and neonatal periods impacts the risk of developing chronic adult diseases and disorders, such as diabetes and obesity [1,2,3,4]
We found that the total amount of milk lipid produced over 24 hrs by high fat (HF)-Ob dams was only about 50% of that produced by HF-fed lean (HF-Ln) dams (Figure 1B, p,0.002), suggesting that maternal obesity impairs milk lipid production
Consistent with evidence that medium chain fatty acids account for the majority of de novo synthesized lipids in milk [30], we found that the total daily production of medium chain fatty acids (MCFA) were significantly decreased in HF-fed obese (HF-Ob) milk compared to HF-Ln milk (Figure 1F, p,0.01)
Summary
Nutrition during fetal and neonatal periods impacts the risk of developing chronic adult diseases and disorders, such as diabetes and obesity [1,2,3,4]. Breast milk, which is considered the ‘‘gold standard’’ for neonatal nutrition, has been linked to numerous health benefits for human infants, including reduced risk of developing obesity [5]. It has been reported that maternal obesity can interfere with the ability to initiate and sustain lactation [6,7], minimizing the potential benefits of breastfeeding for developing infants. Breast milk lipids provide a major source of calories and essential fatty acids necessary for membrane synthesis and neonatal brain development [8,9,10]. Preclinical evidence suggests that high fat (HF) feeding and/or obesity may delay mammary gland development [11,12], and reduce the transfer of essential fatty acids to offspring through milk [3,9,13]. Dietor obesity-induced defects in lactation and/or milk lipid production pose potential risks for growth or developmental abnormalities in breastfed offspring
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
