Maternal Obesity Reduces Milk Lipid Production in Lactating Mice by Inhibiting Acetyl-CoA Carboxylase and Impairing Fatty Acid Synthesis

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.

Early infant adipose deposition is positively associated with the n-6 to n-3 fatty acid ratio in human milk independent of maternal BMI

“…Further, MCFA that are synthesized de novo exclusively by the mammary epithelium 46 were significantly lower in the OB group HM in transitional HM relative to the NW and OW groups. We have observed suppressed MCFA in diet-induced obese mice, in which maternal obesity leads to milk with lower amounts of de novo -derived lipids 47, 48 . Based on our findings here, and previous lactation studies in diet-induced obese mice, we conclude that maternal obesity influences the long-chain PUFA and MCFA amounts in HM.…”

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

“…The combination of maternal obesity and HFD consumption reduces breast milk lipids, whilst HFD consumption during lactation alone increases them (Rolls et al, 1986). Breast milk lipid content is decreased in HFD-fed obese dams during lactation compared to HFD-fed control dams, due to impaired mammary fatty acid synthesis (Saben et al, 2014). In a maternal DIO rat model, breast milk levels of triglycerides are elevated but free fatty acids are decreased early in lactation and increased in the latter stages (Kirk et al, 2009).…”

Elevated dairy fat intake in lactating women alters milk lipid and fatty acids without detectible changes in expression of genes related to lipid uptake or synthesis

“…Although considerable excellent research has been devoted to studying regulation of milk production in the lactating rodent (eg, Refs. [5][6][7]), previous efforts to study gene expression in the lactating human mammary gland have been hindered by difficulty with obtaining mammary biopsy samples from healthy, lactating women. However, a promising noninvasive technique using RNA extracted from the milk fat globule (MFG) has recently been developed (eg, Refs.…”