Leptin is a hormone predominantly made by adipose cells and enterocytes in the small intestine that plays a role in regulating energy balance by inhibiting hunger, which diminishes fat storage in adipocytes. Leptin sends signals to the hypothalamus in the brain, allowing adipocytes to communicate with the brain on how much energy is required.
In the article, “A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity Linked Behaviors in Drosophila” Jennifer Beshel et. al studied the effect of the fly leptin analog unpaired 1 (upd1) on obesity related traits in Drosophila. The pathway upd1 suppresses npf activity and thus regulates expression of food related behavior. Antibody staining showed that upd1 is also seen in fat tissue but has no effect on food cue attraction or weight. Upd1 immunostaining showed that lower levels of upd1 were seen in the cell body in the fed state. After staining flies were exposed to a behavioral chamber where they were exposed to filtered air through four ports with one carrying yeast-odorized air mimicking food cues. Flies with knockdown of upd1 showed attraction to food cues as that of flies experiencing starvation. These flies also consumed more food per hour as compared to control groups. Knockdown of upd2 and upd3 had no effect on food cue attraction or feeding. Reintroduciton of upd1, human leptin or upd2 in brain tissue reduced the increase in obesity-related behaviors seen with the absence of upd1. The results show that adipose and brain derived upd and leptin may control features of weight regulation through specific neural circuits. When moved to 30 degrees Celsius flies carrying transgenes Gal80ts combined with elav-Gal4 and UAS-upd1 showed an increase in obesity-related behaviors. Antibody staining was used to identify the neural components behind this circuit. Beshel et. al found that domeless receptor is co-localized with npf which is the Drosophila NPY homolog. These receptors are needed for signaling satiety. Previous research shows the higher the npf activity the higher attraction to food cues. In this study they found that reduction of npf at the level of the cell body in starved flies is avoided in flies with excess upd1. The manipulation of upd1 in neurons impacts obesity-related behaviors such as food cues and food intake that lead to weight gain. This study is unique in that it addresses the neural circuitry behind the leptin analog upd1 found in drosophila.
In the article mentioned above, researchers were analyzing the leptin analog upd1 and it’s effect on obesity-linked behaviors. A recent article published by Pennington Biomedical research center titled “Why Is Obesity So Common in COVID-19 Patients?” analyzes the effect leptin can have on one’s response to a COVID-19 infection. This article looks at not only leptin's role in appetite and metabolism but leptin’s role in fighting infections. Elevated leptin levels inhibit the body’s ability to fight infections. High levels promote a low-grade systemic inflammatory state making it more difficult to fight off an infection such as COVID-19. The article sites Candida Rebello’s study titled “Obesity, the Most Common Comorbidity in SARS-CoV-2: Is Leptin the Link?” which argues that leptin is the link between the high prevalence of obesity as a comorbidity in COVID-19 patients.
All three articles show the importance of the hormone leptin and how further investigation into it’s functionality and the role it can play in both metabolism and infection is important. The discovery that the leptin analog upd1, in Drosophila, acts through a conserved neural circuit in the brain to regulate obesity could lead to future studies on how to reduce leptin levels in humans to lessen the prevalence of comorbidity with infections such as COVID-19. The articles emphasize the importance of understanding the neural mechanisms and pathways behind energy balance in the human body and the role of leptin; highlighting the importance of understanding the hormone and how leptin continues to affect the health of people as new infections and diseases such as COVID-19 come up.
Works Cited:
Beshel, Jennifer, et al. A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila. Cell Metabolism, vol. 25, no. 1, 2017
Rebello, Candida J., et al. Obesity, the Most Common Comorbidity in SARS-CoV-2: Is Leptin the Link? International Journal of Obesity, vol. 44, no. 9, 2020
Why Is Obesity So Common in COVID-19 Patients? Pennington Biomedical Research Center, 24 July 2020, www.pbrc.edu/news/press-releases/?ArticleID=592
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