Obesity has been the subject of many research studies because it is a complex disease that involves many genetic and environmental factors. According to Dr. Chaitanya Gravini’s lecture, obesity rates are expected to project from 45% in 1970 to 74% in 2020. The obesity effect will increase healthcare costs and decrease life expectancy and earnings. However, treatment is not a simple change in diet and exercise because there are underlying influences on a patient’s feeding behavior, energy expenditure, and other processes involved in weight management. Obesity is instead an outcome of the disruption in energy balance. This disease involves a complex process of gene regulation and expression in the nervous system, adipose tissue, and other areas of the body.
Dr. Chaitanya Gravini and his research team are interested in the gene regulation of obesity. They focused on the regulation of hyperphagy-induced obesity by the C2-domain protein CDP138. This protein is involved in the transport of insulin to the plasma membrane in adipose tissue. CDP138 is co-localized with melanocortin-4 receptor (MC4R), which is an important protein involved in satiety, energy expenditure, and weight loss once activated. Researchers altered the expression level of CDP138 to determine the resulting impact on feeding behavior, energy expenditure, glucose homeostasis, and autonomic outflow. The loss of CDP138 in mice led to hyperphagia and glucose resistance. Hyperphagia is a behavior characterized by excessive hunger and increased food intake. A mutation on CDP138 altered MC4R levels at the membrane surface, causing an increase in hyperphagia with minor changes in energy expenditure. This effect led to an increase in the obesity phenotype in mice.
Likewise, the Sciencedaily article “Gene that may strongly influence obesity uncovered” focused on the gene regulation of obesity. University of Toronto researchers investigated an obesity-linked gene called the foraging gene. This gene is found in the nervous system, muscle, and fat in both humans and flies. It is involved in the moving, feeding and fat storage of an organism. Researchers used fruit flies to understand the effects of gene expression on their feeding behavior and level of obesity. They used homologous recombination to delete the foraging gene in some experimental groups and used recombineering to reintegrate a full copy of this gene in other experimental groups. The deletion of the foraging gene led to a decreased food intake behavior and an increase in triglyceride levels, which suggested a lower energy expenditure and a higher obesity rate. The high expression of the foraging gene led to a higher energy expenditure and less food intake, which decreased the obesity rate.
In both lecture and article, obesity has been shown to be a complex disease that is linked to multiple genes such as the CDP138 and the foraging gene. These genes regulate feeding behaviors, energy expenditure, and other similar metabolic behaviors. Likewise, both research teams manipulated the expression level of their respective gene and observed the obesity effects in their subjects. The upregulation of both CDP138 and the foraging gene led to a decrease in obesity rate whereas the downregulation of both genes led to a higher obesity rate. Each gene had a different mechanism to increase or decrease body weight. For example, a loss of CDP138 increased hyperphagia whereas the loss of the foraging gene led to a decreased movement and energy expenditure. Although these mechanisms are different, they resulted in the same increase in the obese phenotype. Both lecture and article showed that genetic changes can influence obesity and further complicate the solution beyond simple diet and exercise changes. Both research teams aim to understand this disease on the molecular level and contribute more knowledge to a potential treatment that could improve the health and well-being of many obese patients.
Works Cited
Krashes, M. J., Lowell, B. B., & Garfield, A. S. (2016). Melanocortin-4 receptor–regulated energy homeostasis. Nature Neuroscience, 19(2), 206–219. http://doi.org/10.1038/nn.4202
University of Toronto. (2017). Gene that may strongly influence obesity uncovered. ScienceDaily. www.sciencedaily.com/releases/2017/02/170221142049.htm
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