Leptin and its Effects on Pregnancy and Newborns
By Lakshmi Somasundaram
Lakshmi here checking in for Team Green Tea. This week’s blog will focus on the effects of leptin on pregnancy and newborn infants, but first I would like to give some background information on leptin in case it has been awhile since you read our last blog post.
As Matthew explained in the previous blog post, leptin is a hormone secreted by white adipose tissue (fat) in order to inform the rest of the body that energy reserves (in the form of fat) are present and eating is not necessary. Leptin’s primary target is the hypothalamus, an area of the brain highly involved with the regulation of feeding. Rats with a damaged lateral hypothalamus became thin and anorexic while rats with a damaged ventromedial hypothalamus became obese, showing the importance of the hypothalamus with regards to food and appetite. The hypothalamus contains lots of Ob-Rb receptors, a specific form of the general Ob receptor to which leptin binds. Individuals with an ob/ob genotype cannot produce any leptin and individuals with a db/db genotype have no Ob-Rb receptors. Both genotypes results in the same behavior: non-stop eating, which eventually leads to obesity or hyperphagia (an increased appetite for food associated with damage to the hypothalamus).
Amenorrhea refers to the absence of menstruation, and hypothalamic amenorrhea is the absence of menstruation due to disrupted signaling between the hypothalamus and pituitary gland. Normally, the hypothalamus secretes gonadotropin releasing hormone (GnRH) in pulses, which stimulates the pituitary gland. The hypothalamus, pituitary gland, and gonadal glands often act in synchrony with one another and are thus sometimes referred to as the ‘hypothalamic-pituitary-gonadal axis.’ The pituitary gland in turn secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH) into the bloodstream. Both FSH and LH are key hormones for menstruation. According to the research paper Leptin is an effective treatment for Hypothalamic Amenorrhea, “hypothalamic amenorrhea is characterized by cessation of menstrual cycles because of dysfunction of the hypothalamic-pituitary-gonadal axis, abnormalities in gonadotropin pulsatility, and subsequent estrogen deficiency.” It had been shown before that women with hypothalamic amenorrhea often have low leptin levels and that starved mice developed a leptin deficiency and disrupted gonadal glands. Thus, these research scientists administered metreleptin, a synthetic analog of leptin to a group of 11 women with hypothalamic amenorrhea over 36 weeks and observed the effects. Over the 36 weeks, 7 of the 10 women began menstruating, compared to only 2 of 9 women in the control group (the women in the control group would have been told they were receiving a drug that would help induce menstruation, but the drug they received and took actually had no significant effects on the body). Low levels of leptin are now thought to inhibit the release of GnRH, one of the key hormones involved in regulating menstruation. This inhibition thus leads to the absence of menstruation and infertility. Although there were some flaws with the experimental design of this trial, including the low number of participants (increasing the likelihood that outside individual variables had an effect on the outcome of the study), the use of metreleptin hormone to treat individuals with hypothalamic amenorrhea may soon become a reality.
As previously mentioned in this blog post, the main target of leptin is the hypothalamus. A rise in leptin is detected in the hypothalamus by the arcuate nucleus specifically, which then activates neurons in the lateral hypothalamus to inhibit feeding. Before a child is born, its feeding circuitry is already developing, meaning the prenatal environment may have major consequences on the development of this feeding circuitry involving the hypothalamus. The review paper Embryonic development of the hypothalamic feeding circuitry: Transcriptional, nutritional, and hormonal influences states that leptin is a neurotrophic factor, meaning that it supports the growth and specialization of developing neurons, and that the embryonic brain is very susceptible to leptin. It has been found that the placenta in rodents is permeable to leptin, but the placenta itself does not produce leptin. This means that the amount of leptin the embryo is exposed to is entirely dependent on the mother and her diet. In addition, a leptin surge has also been observed in infants after birth. In newborn mice, the absence of this leptin surge led to the failure of the arcuate nucleus within the hypothalamus to form connections with the paraventricular nucleus also within the hypothalamus, which is important for controlling stress, growth, reproduction, and several other autonomic activities. An artificially produced leptin surge during adulthood did not produce these connections, indicating that timing is extremely important. Clearly, leptin plays a crucial role in our bodies, and more research must be done to discover its effects and how to maintain an ideal level through a controlled diet.
Chou, Sharon H., John P. Chamberland, Xiaowen Liu, Giuseppe Matarese, Chuanyun Gao, Rianna Stefanakis, Mary T. Brinkoetter, Huizhi Gong, Kalliopi Arampatzi, and Christos S. Mantzoros. “Leptin Is an Effective Treatment for Hypothalamic Amenorrhea Sharon H. Choua , John P. Chamberlanda , Xiaowen Liua , Gi.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 25 Feb. 2011. Web. 29 Apr. 2017.
Mackay, Harry, and Alfonso Abizaid. “Embryonic Development of the Hypothalamic Feeding Circuitry: Transcriptional, Nutritional, and Hormonal Influences.” Molecular Metabolism3.9 (2014): 813–22. Web. 29 Apr. 2017.