Activation of the Hedgehog protein pathway: A potential solution to obesity?

By Nicholas Persaud

The United States has faced many epidemics in which diseases and illnesses have had adverse effects on the health and wellbeing of Americans. When we think of epidemics we typically think of Ebola, malaria, the flu, or anything that is infectious. However, the United States has been facing a different kind of epidemic for some time now, one that’s not caused by a virus or bacterium. This epidemic is obesity. Obesity affects children and adults alike, with 78 million adults and 13 million children in the US reported to be obese. The major issue with obesity is not the state of being overweight in and of itself but the many serious health complications that accompany it, which include diabetes, heart disease, cancer, and more. As a result, there has been a great government effort to reduce obesity in children and adults by attempting to change people’s eating and exercise habits. However, this is not the most effective solution since it’s very difficult for people to change their lifestyles. Fortunately, recent research shows that there might be a more effective solution to the obesity epidemic.

A team of researchers at the Washington University School of Medicine published a paper titled “Hedgehog signaling via Gli2 prevents obesity induced by high-fat diet in adult mice”. The experiment focuses on the functioning of the Hedgehog, or Hh, signaling pathway. This pathway is well known for its role in tissue development and homeostasis, but previous research has also shown its effects on adipose tissues (body fat). Specifically, activation of the Hh signaling pathway has been shown to inhibit adipose tissue formation. The researchers from Washington University School wanted to test the effects of activating the Hh signaling pathway on a high fat diet, using mice in experimental and control groups by varying the diet and activation of the Hh pathway. The Hh signaling was activated by using genetic engineering.

The results of the experiment were very interesting. As expected, the control group of mice with inactivated Hh pathways and diets high in fat became obese. On the other hand, the experimental mice with activated Hh pathways and high fat diets were not obese and were comparable to the mice who had normal diets. Furthermore, the researchers found that the mice with activated Hh pathways had low blood-glucose levels.

These results imply that it’s possible to prevent the onset of obesity and treat diabetes through the activation of the Hh pathway. As exciting as this sounds, it’s a bit too good to be true. The fact of the matter is that this has only been tested on mice and not on humans, and a report shows that the researchers have said “Translating the findings to humans could be tricky”. Yes, mice are considered to be model organisms due to their genetic similarities, so there is some hope that these findings can be applied to humans. However, activating the Hh pathway in humans could also have undesirable effects such as cancer. If further research into this topic manages to find a way to increase Hh pathway activity in humans without any negative side effects, then it’s possible that this pathway could be used to put an end to the obesity epidemic.

Image found on https://medium.economist.com/the-strange-life-of-a-laboratory-mouse-fdcfae80cb2d

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