Hypoadiponectinemia in Lean Lactating Women: Prolactin Inhibits Adiponectin Secretion from Human Adipocytes

Abstract

Abstract. Adiponectin is an adipocyte-derived hormone involved in glucose, lipid and energy metabolism. A low plasma adiponectin concentration is associated with insulin resistance, obesity and atherosclerosis. In women, energy homeostasis is remarkably changed during gestation and lactation in order to supply sufficient nutrition for a fetus or newborn. In this study we aimed to elucidate the physiological impact of gestation and lactation on the plasma adiponectin levels and the influence of reproduction-related hormones on adiponectin secretion. We studied the longitudinal changes in plasma adiponectin concentration during pregnancy (1st, 2nd and 3rd trimester) and lactation (3 days and 1 month after the delivery) in lean healthy women (n = 22). The plasma adiponectin level declined slightly as the pregnancy advanced and reached its lowest level during lactation (12.25 ± 0.182 µg/ml at early pregnancy vs. 6.88 ± 0.375 µg/ml at 3 days postpartum, p<0.001). In order to investigate the role of the lactogenic hormone prolactin in the decrease of plasma adiponectin levels during lactation, we further performed in vitro experiments using human primary cultured adipocytes. Western blotting of the adipocyte lysate and ELISA of the culture medium revealed that exogenous prolactin inhibited both production and secretion of adiponectin in a dose-dependent manner. Our results thus suggests that prolactin affects the regulation of maternal metabolism through suppression of adiponectin. DURING pregnancy and lactation, the maternal metabolism is dynamically altered in order to provide adequate nutrition to the fetus and newborn. Gestational insulin resistance appears from mid-pregnancy, and this facilitates efforts to supply energy substrate to the fetus, which preferentially uses glucose as an energy source [1]. For some women, this physiological change results in the development of gestational diabetes mellitus, one of the most problematic complications of pregnancy. While the gestational glucose intolerance rapidly improves after the delivery, maternal carbohydrate and energy metabolism remains altered during lactation in order to satisfy the glucose demand in milk synthesis [2][3][4][5]. Although these physiological alterations in glucose and energy metabolism during pregnancy and lactation have been well recognized, the mechanisms underlying this phenomenon are not fully understood.Adiponectin is an adipocytokine that is predominantly produced by adipocytes and secreted into plasma at high levels. This 30 KDa peptide hormone possesses insulin-sensitizing, antiatherogenic properties and its plasma level inversely correlates with obesity [6][7][8][9][10]. Most recently, Qi et al. reported that intracerebroventricular administration of adiponectin stimulated energy expenditure in mice, suggesting that adiponectin acts on the central nervous system to regulate energy metabolism [11]. Because adiponectin has a variety of effects on glucose and energy metabolism, it is reasonable to hypothesize that adiponectin plays a

Prolactin upregulates its receptors and inhibits lipolysis and leptin release in male rat adipose tissue

“…Whereas serum adiponectin levels are unchanged in PRLR- [6] or PRL-knockout mice [25], PRL at very high doses inhibits adiponectin production in cultured human adipose tissue and in mice in vivo [6,31]. Lower circulating adiponectin levels were reported in lactating women, with inhibition of adiponectin production in cultured human adipocytes by PRL [32]. These discrepancies are likely due to differences in experimental design, doses of PRL, gender or species.…”

Pre- and early post-partum adiponectin and Interleukin-1beta levels in women with and without gestational diabetes

“…39 On the other hand, other investigators found hypoadiponectinemia during the 3 rd and 4 th day postpartum in normal lactating women. 40,18 It has been suggested that this hypoadiponectinemia might be due to the suppression of adipocyte-produced adiponectin by prolactin. 40,41 Otherwise, the significant decrease of the studied cytokines during the early postpartum period in pregnancies with GDM in this study could be explained by the withdrawal of cytokines produced by the placenta during pregnancy.…”

“…40,18 It has been suggested that this hypoadiponectinemia might be due to the suppression of adipocyte-produced adiponectin by prolactin. 40,41 Otherwise, the significant decrease of the studied cytokines during the early postpartum period in pregnancies with GDM in this study could be explained by the withdrawal of cytokines produced by the placenta during pregnancy. 8,9,27 The role of the placenta in the production of adiponectin and IL-1β during pregnancy is further reinforced by the non-significant but clear downward trend of these cytokines during third day postpartum found in pregnancies without GDM.…”

The STAT5A-Mediated Induction of Pyruvate Dehydrogenase Kinase 4 Expression by Prolactin or Growth Hormone in Adipocytes

“…One study conducted in lean pregnant women demonstrated that PRL could cause insulin resistance in adipocytes by suppressing adiponectin production and secretion (38). This mechanism is plau- sible, because low levels of adiponectin can be associated with obesity and insulin resistance.…”