Lactation alters the relationship between liver lipid synthesis and hepatic fat stores in the postpartum period

Abstract

In mothers who are nursing their infants, increased clearance of plasma metabolites into the mammary gland may reduce ectopic lipid in the liver. No study to date has investigated the role of lactation on liver lipid synthesis in humans, and we hypothesized that lactation would modify fatty acid and glucose handling to support liver metabolism in a manner synchronized with the demands of milk production. Lactating (n = 18) and formula-feeding women (n = 10) underwent metabolic testing at 6-week postpartum to determine whether lactation modified intrahepatic triacylglycerols (IHTGs), measured by proton magnetic resonance spectroscopy. Subjects ingested oral deuterated water to measure fractional de novo lipogenesis (DNL) in VLDL-TG during fasting and during an isotope-labeled clamp at an insulin infusion rate of 10 mU/m²/min. Compared with formula-feeding women, we found that lactating women exhibited lower plasma VLDL-TG concentrations, similar IHTG content and similar contribution of DNL to total VLDL-TG production. These findings suggest that lactation lowers plasma VLDL-TG concentrations for reasons that are unrelated to IHTG and DNL. Surprisingly, we determined that the rate of appearance of nonesterified fatty acids was not related to IHTG in either group, and the expected positive association between DNL and IHTG was only significant in formula-feeding women. Further, in lactating women only, the higher the prolactin concentration, the lower the IHTG, while greater DNL strongly associated with elevations in VLDL-TG. In conclusion, we suggest that future studies should investigate the role of lactation and prolactin in liver lipid secretion and metabolism.

Keywords: VLDL; hormones; lipogenesis; liver metabolism; mammary gland; nonesterified fatty acids; pregnancy; prolactin; triacylglycerol.

Figure 1

Insulin and glucose concentration immediately before and during an insulin infusion rate of 10 mU/m²/min and glucose infusion rate during insulin administration. A: Plasma insulin concentration at baseline and during insulin infusion. Baseline insulin concentrations were averaged for each postpartum woman using measurements from 95, 105, 115 min (before insulin) and from 215, 225, 235 min (end of insulin exposure at this rate). B: Glucose concentration at baseline (t = 120 min) immediately before insulin administration and during a 120-min clamp (t = 120–240 min) using an insulin infusion rate of 10 mU/m²/min. C: Units per hour of insulin infused during an insulin infusion rate of 10 mU/m²/min. D: Glucose infusion rate during the clamp. Data are mean ± SD. Filled bars and filled circles represent lactating women. Open bars and open circles represent formula-feeding women.

Figure 2

Effect of lactation on glucose production and FFA turnover. Data are mean ± SD and demonstrate the response of (A) endogenous glucose production (EGP) and (B) the rate of appearance of nonesterified fatty acid (RaFFA) during baseline (fasting state before exogenous insulin) and during the clamp with a low insulin infusion rate (10 mU/m²/min) for lactating (n = 18) and formula-feeding (n = 10) women. Measurements in the fasting state are the average for each postpartum woman using measurements from 95, 105, 115 min (before insulin) and from 215, 225, 235 min (end of insulin exposure at this rate). Interactions between feeding group (lactating vs. formula feeding) and exogenous insulin (insulin infusion rate of 0 or 10) were assessed with repeated-measures ANOVA. Statistical analyses are shown below each respective figure panel.

Figure 3

Effect of lactation and a hyperinsulinemic clamp on VLDL-TG and de novo lipogenesis. Data are mean ± SD and demonstrate the concentrations of plasma TG carried in very low-density lipoproteins (VLDL-TG in panel A), the fractional de novo lipogenesis in VLDL-TG (DNL %, panel B), and the absolute DNL (panel C) during fasting and during insulin infusion (10 mU/m²/min). Timing of the infusion is presented for the fasting state (95, 105, 115 min) and at the end of the insulin infusion (215, 225, and 235 min). Interactions between feeding group (lactating vs. formula feeding) and exogenous insulin (insulin infusion rate of 0 or 10) were assessed with repeated-measures ANOVA. Statistical analyses are shown next to each respective figure panel. DNL, de novo lipogenesis.

Figure 4

Relationships between fasting prolactin concentrations, IHTG, VLDL-TG, and fasting DNL. Spearman correlation analyses of associations between fasting prolactin concentrations and intrahepatic-TG (IHTG, panel A, lactating and formula group sample sizes n = 18 and 9, respectively), VLDL-TG concentration (panel B, n = 18 and 9), and fasting fractional de novo lipogenesis (DNL percent, panel C, n = 17 and 10). DNL, de novo lipogenesis; IHTG, intrahepatic triacylglycerol.

Figure 5

Relationships between liver fat, fasting RaFFA, DNL and VLDL-TG, and the quantity of glucose infused during the clamp. Spearman correlation analyses of associations (r, P-value) between the sources of liver fat from RaFFA (panel A, lactating and formula group sample sizes n = 16 and 9, respectively) and from fasting DNL (panel B, n = 17 and 9). Panel C shows the relationships between fractional DNL and VLDL-TG concentration in the fasting state (n = 17 and 9). Panel D demonstrates the lack of significant relationships between the total quantity of glucose infused during the clamp and the level of DNL at the end of the clamp (n = 18 and 10). DNL, de novo lipogenesis; RaFFA, rate of appearance of nonesterified fatty acids.