Novel Approaches to Combating Obesity

When it comes to eating in the healthiest way possible, the literature is conflicting. If you ask one side, a low-fat diet with plenty of whole grains is a sure path to optimal health, and if you ask the other, a low-carbohydrate diet that is high in certain fats is guaranteed to make you leaner and healthier. While the optimal diet for being healthy and losing weight might be in constant debate, there is little debate about the seriousness of the obesity epidemic. On a societal scale, it costs us billions of dollars each year, and on a personal level, people’s fathers, mothers, brothers, and sisters are facing serious complications due to their excess weight.

On October 1^st, Dr. Beshel, an Assistant Professor at Loyola University studying the neural circuits that control feeding, highlighted a key point in her talk on combatting the obesity epidemic: things were not always this way. As she noted in her talk, over the last several decades, the food landscape has changed, and with that change, came an alarming rise in the rates of obesity. Sadly, the new food landscape is not likely to change anytime soon, but that highlights the need for new avenues of research to combat this problem.

Dr. Beshel’s research focuses on the neural circuitry that governs energy homeostasis. In her 2013 paper, Graded Encoding of Food Odor Value in the Drosophila Brain, she characterized dorsomedial Drosophila neuropeptide F (dNPF) positive neurons in the Drosophila brain. dNPF is the functional homolog to neuropeptide Y (NPY), an orexigenic or hunger promoting peptide produced by NPY positive neurons in the arcuate nucleus of the hypothalamus. The dorsomedial dNPF cells encode food odor value by responding specifically to food odors, and their activity directly correlates with food-seeking behavior. While her 2013 paper only looked at the characteristics of specific neurons, her 2017 paper, A Leptin Analog Locally Produced in the Brain Acts via a Conserved Neural Circuit to Modulate Obesity-Linked Behaviors in Drosophila, characterized an energy homeostatic pathway in Drosophila that is functionally conserved with the mammalian leptin circuit.

In mammals, leptin that is produced by the adipose tissue enters the bloodstream, crosses the blood-brain barrier, and enters the hypothalamus where it binds to its cognate receptor to inhibit orexigenic NPY positive neurons. In Drosophila, neuronally produced unpaired 1 (upd1), a cytokine with an analogous function to leptin, binds to domeless receptors on the previously discussed dorsomedial dNPF cells, inhibiting the orexigenic cells which reduces food-seeking behavior. With this conserved homeostatic circuit that show homology between the domeless receptor and the leptin receptor and dNPF and NPY, Dr. Beshel hopes to develop a model of obesity in flies that can help elucidate the biological underpinnings of obesity. While a neurobiological homeostatic approach is novel and interesting, this is not the only novel approach to combatting obesity.

The NY times article Seeking an Obesity Cure, Researchers Turn to the Gut Microbiome highlights the research of Dr. Elaine Yu. Dr. Yu. is trying to determine if the microbiome has an effect on obesity. There are some preliminary studies that show a difference in the microbiome of obese and lean individuals. Additionally, a case study involving a woman with a C. diff infection documented a 34-pound weight gain after she received a fecal matter transplant (FMT) from her obese daughter. With these interesting preliminary studies and case studies in mind, Dr. Yu took a group of 24 obese men and women and four lean microbiome donors to determine if the implantation of the lean persons’ microbiomes into the obese individuals has an effect on their obesity phenotype. She did this by taking stool samples from the lean donors and converting the samples to ingestible capsules for the obese individuals to take weekly. Twelve of the obese individuals were given FMT capsules and the other half were given placebo over the course of twelve weeks. Unfortunately, the study resulted in no difference between groups, but this was a small study in a still burgeoning area of research. More studies need to be done in order to determine how the microbiome affects energy homeostasis and metabolism.

Both Dr. Beshel and Dr. Elaine Yu are seeking new and interesting ways of combatting the obesity epidemic. Dr. Beshel’s work is at the phase of looking for new potentially druggable targets within the homeostatic pathways she studies. Dr. Yu is in the clinical phase where she is looking at the direct effects of an intervention on obese individuals. Hopefully, these new approaches will help uncover new tools to combat the rise of obesity around the world.

Works Cited

Beshel, J., and Zhong, Y. (2013). Graded Encoding of Food Odor Value in the Drosophila Brain. J. Neurosci. 33, 15693–15704.

Beshel, J., Dubnau, J., and 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, 208–217.

O'connor, A. (2019, September 10). Seeking an Obesity Cure, Researchers Turn to the Gut Microbiome. Retrieved October 13, 2019, from https://www.nytimes.com/2019/09/10/well/eat/seeking-an-obesity-cure-researchers-turn-to-the-gut-microbiome.html