COGS 163 Brainiacs Blog Post 3 — Leptin and Reproductive Systems
Welcome back Leptin fanatics, it’s Pari from the Brainiacs ready to get down to the nitty gritty; we’re not talking about the birds and bees here, but more specifically to continue the discussion regarding Leptin associated with feeding efficiency and to touch upon the importance of Leptin in our reproductive systems.
I’d like to bring us back to about eleven hours ago. Within that time (in some divine miracle), I had just taken my last couple strides to completing my first half marathon.
As my body’s momentum finally came to a screeching halt, I could feel every ounce of my body shutting down. I had just exerted all my energy to get through that last mile. My head was throbbing, my breath was short, and I felt like I was falling through the depths of hell. I’m being dramatic, but from a biological standpoint my body was not, it was simply SCREAMING with frustration. From waking up at 5am to running through the finish line of the half marathon around 11:30am, I had spent 6 hours exerting energy, and had failed to give my body fuel throughout the day like I normally would. Feeling winded, I sat and took a breath. As my body began to regulate again, one thing became very clear: the Leptin in my body was requesting the need for Neuropeptide Y (NPY) to signal feeding in my body! (aka, I was incredibly hungry).
Let us recall, Leptin is our body’s feeding signal, alerting the brain through stimulation of the Orexogenic “to eat” pathways or Anorexogenic “no eat” pathways. While the Anorexogenic pathway inhibits feeding through a decrease of food intake by POMC and CART, the Orexogenic pathway promotes feeding and the increase of food intake through AgRP, NPY, Orexin and Galanin. Moments before the race ended, I began to think about how incredible a baked bear mint chocolate chip ice cream sandwich would sound. Similar to how your body is most likely reacting now, this caused a cascade of insulin release which in-turn prepared my body for what it was extremely eager to ingest. Insulin then signaled NPY by binding to receptors and attaching to NPYR-5. This then stimulated the Lateral Hypothalamic Area which in turn stimulated the Orexogenic “eat” pathway.
In order to prevent one from eating 2–3 of these ice-cream sandwiches after a race (believe ME, this still may have been possible), the brain must be able to identify the amount of Leptin that has been used, allowing Leptin to bind to the OBRb receptor, signaling the Anorexigenic “no eat” signal through POMC, decreasing food intake as well as feeding efficiency. CART receptors are also in effect here, however the OBRb receptor signals CART by binding to NPY-5 once more, signaling the Orexigenic “eat” pathway once more.
Now I’m sure you’re starting to wonder how this ties in to our reproductive systems and reproduction. Let’s take a closer look.
For those who are healthy, or have normal functioning leptin receptors, it is extremely easy for a fetus to grow within the mother’s body because the mother is well-nourished. Mal-nourishment due to a decrease in feeding (inability to inhibit the anorexigenic “no eat” pathway) creates a low probability for a child to be born. This is due to symptoms that arise from anorexia. When the mother becomes malnourished or characterized as anorexic, she will often have reduced levels of estrogen which cause reductions or eradication of menstruation. This occurs because Leptin regulates how much adipose tissue is available for energy release in the body. Similarly, Leptin signals hormone release from the pituitary glands, stimulating ovulation, and later monitoring the menstrual cycle as well. On the other hand, having too much food as a pregnant mother doesn’t help one’s case either. Obesity during pregnancy causes a surge in glucose levels, leptin, and other neuropeptides that create an unbalance in homeostatic regulation of menstruation. This causes a number of different deficits such as gestational diabetes and also affects hypothalamic development.
While many believe non-functioning Leptin receptors are a lost cause, Metreleptin has been analogous to Leptin action, stimulating the release of luteinizing hormone (same hormone released by Leptin) to aid the menstrual cycle. While this is no quick fix, Metreleptin is an incredible breakthrough that has allowed for communication between the uterus and hormones such as Estrogen and Progesterone, all crucial aspects of female reproduction pathways.
I hope this provided some insight onto neural mechanisms underlying Leptin and Orexigenic/Anorexigenic pathways. Next time someone asks you about the birds and the bees, feel free to throw this story at them. We’ll catch you back here next week!
- Chou, H. & Mantzoros, C. (2014). Role of leptin in human reproductive disorders. Thermatic Review. 223:1.
- Chou, H., Chamberland, J.P., Liu, X., Matarese, G., Gao, C., Stefanakis, R., Brinkoetter, M.T., Gong, H., Arampatzi, K., & Mantzoros, C.S. (2011). Leptin is an effective treatment for hypothalamic amenorrhea. PNAS, 108(16), 6587. Retrieved from http://pages.ucsd.edu/~mboyle/COGS163/pdf-files/Leptin%20is%20an%20effective%20treatment%20for%20amenorrhea-2011-Chou-6585-90.pdf
- Chehab, F. (2014). Leptin and reproduction: past milestones, present undertakings, and future endeavors. Journal of Endocrinology. 233, T37-T48. Retried from http://pages.ucsd.edu/~mboyle/COGS163/pdf-files/Leptin%20and%20reproduction-20-year-review.pdf