Nonadipose tissue production of leptin: Leptin as a novel placenta-derived hormone in humans

Abstract

Leptin is a circulating hormone that is expressed abundantly and specifically in the adipose tissue. It is involved in the regulation of energy homeostasis, as well as the neuroendocrine and reproductive systems. Here, we demonstrate production of leptin by nonadipose tissue, namely, placental trophoblasts and amnion cells from uteri of pregnant women. We show that pregnant women secrete a considerable amount of leptin from the placenta into the maternal circulation as compared with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was augmented during the course of forskolin-induced differentiation of cytotrophoblasts into syncytiotrophoblasts. Plasma leptin levels were markedly elevated in patients with hydatidiform mole or choriocarcinoma and were reduced after surgical treatment or chemotherapy. Leptin is also produced by primary cultured human amnion cells and is secreted into the amniotic fluid. The present study provides evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.

Effect of placental function on fatty acid requirements during pregnancy

“…Placentally derived leptin is a potent stimulator of lipolysis (Masuzaki et al, 1997;Gomez et al, 1999;Fruhbeck et al, 2001) which the human placenta exports into both the maternal and fetal circulation (Linnemann et al, 2000;Hoggard et al, 2001). The rate of placental leptin export into the maternal circulation increases with increasing fetal to placental weight ratio (Hoggard et al, 2001), suggesting that the placenta may modulate its own substrate supply in response to the fetal demand.…”

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

“…In fact, the administration of this hormone, while proven to be effective in reducing fat and normalizing metabolic disorders in leptin-deficient mice and humans, has not proven to be effective in most cases of obesity. 4,[8][9][10] Although leptin is mainly produced by the adipose tissue, this hormone is also produced by other tissues, such as stomach, [11][12][13] placenta, 14,15 skeletal muscle 16 and mammary epithelium, 17 and it is naturally present in maternal milk. 18,19 Although leptin produced by the adipose tissue is known to play a main role in the chronic control of energy balance, the role of leptin produced by the stomach has been related with the short-term control of food intake, acting as a satiety signal.…”

Leptin and phospholipid-esterified docosahexaenoic acid concentrations in plasma of women: observations during pregnancy and lactation

“…Our study further indicated that this pregnancyrelated increase in leptin concentration starts within the ®rst 2 ± 3 weeks after conception. It is suggested that the placenta is a major source of maternal leptin during pregnancy (Masuzaki et al, 1997;Sen Äaris et al, 1997). Considering the fast increase in leptin concentration during the ®rst weeks of pregnancy, other sources of leptin might be involved.…”

“…During pregnancy, a marked increase in the maternal serum leptin concentration occurs, which is followed by a sharp decrease immediately after delivery (Butte et al, 1997;Hardie et al, 1997;Sattar et al, 1998;Schrubing et al, 1998). Several studies have demonstrated that, aside from adipose tissue, the human placenta also synthesizes leptin (Masuzaki et al, 1997;Sen Äaris et al, 1997). Hormones like human chorionic gonadotrophin (hCG), luteinizing hormone (LH), estradiol and insulin may promote leptin release from maternal adipocytes and contribute to the hyperleptinemia (Hardie et al, 1997;Lepercq et al, 1998;Licinio et al, 1998;Sivan et al, 1998).…”