Fetal Leptin Is a Signal of Fat Mass Independent of Maternal Nutrition in Ewes Fed at or above Maintenance Energy Requirements1

Abstract

In adults, circulating leptin concentrations are dependent on body fat content and on current nutritional status. However, the relationships among maternal nutrient intake, fetal adiposity, and circulating leptin concentrations before birth are unknown. We investigated the effects of an increase in nutrient intake in the pregnant ewe on fetal adiposity and plasma leptin concentrations during late gestation. Between 115 and 139-141 days gestation (term = 147 +/- 3 days gestation), ewes were fed a diet calculated to provide either maintenance (control, n = 6) or approximately 155% of maintenance requirements (well-fed, n = 8). The fetal fat depots (perirenal and interscapular) were dissected, and the relative proportion of unilocular and multilocular adipocytes in each depot was determined. Maternal plasma glucose and leptin concentrations were significantly increased in well-fed ewes. Fetal plasma glucose concentrations were also higher in the well-fed group (115-139 days gestation: control, 1.65 +/- 0.14 mmol/L; well-fed, 2.00 +/- 0.14 mmol/L; F = 5.76, P < 0.04). There was no effect of increasing maternal feed intake on total fat mass, the relative mass of unilocular fat, or fetal plasma leptin concentrations (115-139 days gestation: control, 5.2 +/- 0.8 ng/ml; well-fed, 4.7 +/- 0.7 ng/ml). However, in both the control and well-fed groups fetal plasma leptin concentrations (y) were positively correlated with the relative mass of unilocular fat (x): y = 1.51x + 1.70; (R = 0.76, P < 0.01). Thus, fetal leptin may play a role as a signal of unilocular fat mass in the fetus when maternal nutrient intake is at or above maintenance requirements.

Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity

“…This transfer increases during late pregnancy in parallel with an upregulation of expression of the shorter isoforms of the leptin receptor in the placenta (Smith & Waddell 2002, 2003. In species such as the sheep and pig, in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation through late gestation (Yuen et al 1999, Chen et al 2000, Devaskar et al 2002, Ehrhardt et al 2002, Muhlhausler et al 2002, 2003, Yuen et al 2002. Leptin is also expressed in the fetal sheep brain and liver but, in contrast to the human, leptin is not expressed in the sheep placenta (Thomas et al 2001, Ehrhardt et al 2002.…”

“…Leptin is present in the circulation of the sheep fetus from as early as 40 days gestation, which is before the development of visible adipose tissue depots, and fetal plasma leptin may therefore originate from either the maternal circulation or from fetal tissues other than adipose tissue at this early stage of pregnancy (Ehrhardt et al 2002). Circulating leptin concentrations are lower in the fetus than in the pregnant ewe throughout late gestation (Ehrhardt et al 2002, Muhlhausler et al 2002, Yuen et al 2002. It has been reported that the sheep placenta expresses the leptin receptor gene (Thomas et al 2001) that in the sheep the placental leptin receptor may mediate the uptake of leptin from the maternal into the fetal circulation.…”

“…Ultrastructural studies of adipose tissue in the sheep fetus have demonstrated that fetal adipocytes contain multiple lipid locules and an abundance of mitochondria, and express uncoupling protein 1 (UCP1): characteristic features of thermogenic or brown adipose tissue (Gemmell et al 1972, Gemmell & Alexander 1978, Symonds & Stephenson 1999, Yuen et al 2003. Fetal adipocytes also contain larger or dominant lipid locules and there is a direct relationship between the relative mass of the 'unilocular' component of perirenal and interscapular fat, and circulating leptin concentrations in a cohort of fetuses in well-nourished pregnant ewes (Muhlhausler et al 2002). This suggests that circulating leptin concentrations may be a signal of the unilocular component of fetal fat, rather than total fat mass in fetal life, as it is in the neonate and adult.…”

“…In the sheep, a moderate increase (, 50%) in maternal nutrient intake above maintenance requirements increases maternal plasma glucose and leptin concentrations during late gestation in the absence of a concomitant increase in either total fetal fat mass or fetal plasma leptin concentrations (Muhlhausler et al 2002). In these well-nourished ewes there was, however, a significant relationship between fetal glucose and the relative mass of fetal unilocular fat, and a positive relationship between fetal insulin concentrations and the relative abundance of leptin mRNA in fetal perirenal adipose tissue (Muhlhausler et al 2003).…”

Impact of periconceptional nutrition on maternal and fetal leptin and fetal adiposity in singleton and twin pregnancies

“…In the sheep, as in the human, it has been demonstrated that leptin is synthesized in fetal adipose tissue and is present in the fetal circulation through late gestation (7,10,12,23,34,35). Furthermore, there is evidence that leptin synthesis in fetal adipose tissue is regulated by fetal insulin concentrations and that circulating leptin concentrations are correlated with the relative mass of unilocular fat present in the adipose tissue depots in the sheep fetus during late gestation (term ϭ 150 days gestation; see Refs.…”