Leptin in pregnancy and development: a contributor to adulthood disease?

Abstract

Emerging research has highlighted the importance of leptin in fetal growth and development independent of its essential role in the maintenance of hunger and satiety through the modulation of neuropeptide Y and proopiomelanocortin neurons. Alterations in maternal-placental-fetal leptin exchange may modify the development of the fetus and contribute to the increased risk of developing disease in adulthood. In addition, leptin also plays an important role in reproductive functions, with plasma leptin concentrations rising in pregnant women, peaking during the third trimester. Elevated plasma leptin concentrations occur at the completion of organogenesis, and research in animal models has demonstrated that leptin is involved in the development and maturation of a number of organs, including the heart, brain, kidneys, and pancreas. Elevated maternal plasma leptin is associated with maternal obesity, and reduced fetal plasma leptin is correlated with intrauterine growth restriction. Alterations in plasma leptin during development may be associated with an increased risk of developing a number of adulthood diseases, including cardiovascular, metabolic, and renal diseases via altered fetal development and organogenesis. Importantly, research has shown that leptin antagonism after birth significantly reduces maturation of numerous organs. Conversely, restoration of the leptin deficiency after birth in growth-restricted animals restores the offspring's body weight and improves organogenesis. Therefore, leptin appears to play a major role in organogenesis, which may adversely affect the risk of developing a number of diseases in adulthood. Therefore, greater understanding of the role of leptin during development may assist in the prevention and treatment of a number of disease states that occur in adulthood.

Effects of maternal obesity on placental function and fetal development

“…Leptin deficiency with the loss of placental derived leptin in growth restricted and pre-term delivered offspring contributes to reduced frontal cortex volume and behavioral deficits in rats (Dexter et al 2014). Leptin is believed to impact fetal organ growth, including the brain, appetite regulation, and cognition during early development (Briffa et al 2015). Some authors have suggested that leptin replacement in early life may improve long-term metabolic and behavioral outcomes (Meyer et al 2014; Chen et al 2011).…”

Neuroendocrine-immune circuits, phenotypes, and interactions

“…Encoded by the ob gene, leptin is a peptide hormone produced by adipocytes that has anorexigenic effects upon appetite (Myers et al, 2008). In addition, leptin has well-described effects upon immune function (reviewed by Carlton et al, 2012), reproduction (Caprio et al, 2001; Tena-Sempere, 2007), and development (Briffa et al, 2015; Crespi and Unkefer, 2014). In mammals, experimental reductions in white adipose tissue via surgical removal (i.e., lipectomy) of specific white adipose tissue depots impairs antibody production; immune function is restored following compensatory regrowth of the remaining fat pads (Demas et al, 2003).…”

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

“…Umbilical cord leptin levels are elevated in obese pregnancies (Ferretti et al, 2014;Karakosta et al, 2013;Walsh et al, 2014) and neonatal circulating leptin is elevated in offspring of obese mice (Samuelsson et al, 2008). Therefore, early life hyperleptinaemia may drive sympathetic hyperstimulation in the developing renal-cardiovascular system, leading to hypertension and cardiovascular dysfunction in adulthood (Briffa et al, 2014). Indeed, neonatal leptin administration in rats results in cardiac hypertrophy and dysfunction in adulthood (Marques et al, 2014b).…”