Obesity is one of the leading health issues in America today, affecting around 40% of the US population, according to the CDC. As obesity is so prevalent and is associated with many significant health risks, research into obesity is very prominent and expansive in many fields of science today. In neuroscience, researchers have been looking at the role leptin plays in neural pathways that regulates food and appetite related behavior. This research helps in identifying the causes of obesity.
Leptin is a hormone released by fat cells. It is thought to be a ‘satiety’ signal to the body, thereby controlling food intake and appetite. Leptin is thought to inhibit neurons in the brain that work in neural pathways that promote food intake and stimulate hunger. Dr. Jennifer Beshel conducted a study to see whether reducing expression of an leptin analog in the brain would lead to obesity phenotypes. In the article “A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila”, Dr. Jennifer Beshel and colleagues were studying a leptin analog, upd1, in Drosophila. Upd1 is thought to inhibit Drosophila neuropeptide F (npf), which functions in regulating food odor valuation and promotes food intake. They found that neurons expressing Upd1 are positioned in the brain to release upd1 on npf-positive neurons. This is a homologue of leptin acting on mammalian neuropeptide Y seen in humans which also regulates food related behavior. The researchers also showed that flies that were manipulated to stop expressing upd1 had a greater response to food odor cues, consumed more food per hour compared to controls, had a higher body mass and had increased sensitivity to an obesogenic environment. The results provide evidence for obesity being related to genetics, shown here in the case of leptin expression, and one’s food environment.
Dr. Beshel’s study showed how leptin plays a role in obesity characteristics shown in the body through neural signalling. However, this study led to further questions regarding what controls and mediates leptin levels in the brain. An article published by Science Daily spoke about a recent study led by researchers at Baylor College of Medicine, which offered one explanation of how our 21st century food landscape controls leptin levels. It explained how the researchers were looking at a mechanism that influences ‘leptin resistance’. Leptin resistance is when the body is producing normal levels of leptin but does not respond to its satiety signal. It is thought that the majority of obsese individuals do not have a genetic mutation that stops them producing leptin, but instead have leptin resistance, making it an interesting subject of research. In “Gut-brain connection helps explain how overeating leads to obesity”, the article explained how the researchers were studying gastric inhibitory polypeptide (GIP), a hormone that is produced in the gut which travels to the brain and inhibits leptin. GIP functions in managing the body’s energy levels, and GIP production in the gut is increased when eating a high fat diet. The researchers fed mice a high fat diet, making them obese, and then blocked the GIP receptors in the brain. With GIP not functioning, the mice ate less and were able to reduce their fat mass. This suggests that leptin was now able to function correctly and control appetite. Interestingly, they found that normally fed, lean mice did not respond to blocking GIP receptors, indicating that diet influences this GIP and leptin interaction. The results of this study suggest that a high fat diet contributes to leptin resistance through the role of GIP. In our current food landscape in which more people are eating high fat diets, the interesting results of this study offers more insight into how this diet is affecting obesity.
The results of Dr. Beshel’s and the Baylor College of Medicine’s studies provide us with great insight into starting to understand how obesity happens and how an individual might be predisposed to becoming obese. However, it is clear that more research into leptin, leptin resistance and the factors that influence these mechanisms needs to be done in order to improve our understanding of obesity and help lessen the rate of obesity in the U.S and the world today.
WORKS CITED:
Baylor College of Medicine. (2018) "Gut-brain connection helps explain how overeating leads to obesity." ScienceDaily. ScienceDaily, 12 August 2019. <www.sciencedaily.com/releases/2019/08/190812160533.htm>.
Beshel, J., Dubnau, J., & Zhong, Y. (2017). A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila. Cell metabolism, 25(1), 208–217. https://doi.org/10.1016/j.cmet.2016.12.013
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