Everything you need to know about gene therapy shown to cure type 2 diabetes and obesity in mice, researchers report

A single supervision of an adeno-associated viral vector booming the Fibroblast Growth Factor 21 gene resulted in genetic manipulation of the liver, skeletal muscle or adipose tissue to rapidly enhance Fibroblast Growth Factor 21 protein. This protein is a hormone secreted naturally by several organs that acts on many tissues for the maintenance of correct energy metabolism. By inducing FGF21 production through gene therapy the animal lost weight and decreased insulin resistance, this causes the development of type 2 diabetes.

The therapy has been tested successfully in two different mouse models of obesity, induced either by genetic mutations or diet. Also, the researchers scrutinized that when administered to healthy mice, the gene therapy endorsed healthy aging and prevented age associated weight gain and insulin resistance.

After treatment with adeno-associated viral- Fibroblast Growth Factor 21, mice lost weight and reduced fat accumulation and inflammation in adipose tissue; steatosis, fibrosis and inflammation of the liver were also reversed. This led to an increase in healthy aging and in insulin sensitivity without any adverse side effects.

The results have been reproduced after genetic manipulation of three different tissues to produce the Fibroblast Growth Factor 21. This gives flexibility to the treatment, since it permits to choose each time the most appropriate tissue and in case some impediment prevents manipulating any of the tissues, it can be applied to any of the others. When a tissue produces Fibroblast Growth Factor 21 protein and secretes it into the bloodstream, it will be distributed throughout the body.   

The authors highlight the significance of these results, since the prevalence of type 2 diabetes and obesity is growing at alarming rates around the world. Obesity also enhances the risk of mortality and indicates an important risk factor for neurodegenerative disorders, cardiovascular and immune diseases, arthritis, hypertension, and some types of cancer.

The results also reveal that the scrutinization of the gene therapy ensured against the risk of tumor formation in the liver in response to a hyper caloric diet for a prolonged period of time.

The native Fibroblast Growth Factor 21 protein has a short half-life when administered using conventional procedures. For this reason, the pharmaceutical industry has developed Fibroblast Growth Factor 21 analogues and has already conducted clinical trials. Fibroblast Growth Factor 21 mimetics, however require periodic administration to mediate clinical advantages and but may raise immunological issues related to the administration of exogenous proteins. The gene therapy vectors used by researcher, however, induce the mice to produce for many years the same FGF21 hormone naturally produced by the body, after a single administration and without any adverse effects.

For scientist the next step will be to test this therapy in larger animals before moving to clinical trials with patients. AAV-mediated gene therapy has been approved for the treatment of several diseases, due to its efficacy and safety profile. Similarly, there exists extensive clinical experience in applying adeno associated viral-mediated gene transfer to liver and skeletal muscle. Subsequently, the therapy described in this study comprises the basis for the future clinical translation of Fibroblast Growth Factor 21 gene transfer to treat obesity, type 2 diabetes, and related comorbidities. 

Contact details:

Alina Grace

Program Manager | Obesity Middle East 2019

Email Id: obesityendo@mehealthevents.org

The ultimate revelation of Obesity and Cognitive Function

High intensity interval exercise is commonly recognized as the most time effective and efficient way to exercise. It could likewise be an effective strategy to prevent and combat cognitive dysfunction in obese individuals.

Obesity reduces the expression of brain-derived neurotrophic factor, a protein in the brain that promotes the survival of neurons. Lower levels of this protein are associated with Parkinson's disease, Alzheimer's disease, and obesity. Although research has shown that obesity is a risk factor for cognitive dysfunction, the mechanisms of this relationship are not fully understood.

To-date, studies on exercise and brain-derived neurotrophic factor response in obese individuals have only used continuous moderate intensity exercise without rest intervals. The researchers examine the modulatory role of obesity on exercise-induced BDNF release and to use an acute high-intensity interval exercise protocol as a practical model to measure the phenomena of brain-derived neurotrophic factor response release in both obese and normal-weight subjects. They also examined the potential relationship of an exercise-induced brain-derived neurotrophic factor with blood lactate and cortisol.

Results of study, show that the brain-derived neurotrophic factor response to acute high intensity interval exercise was greater than continuous moderate-intensity exercise in obese subjects when compared to normal weight subjects. These findings recommend that acute high intensity interval exercise may be a more effective protocol to upregulate brain derived neurotrophic factor expression in an obese population, cortisol levels and independent of increased lactate.

Other findings from the study show statistically significant differences between the obese and normal weight groups for body weight, body mass index, systolic and diastolic blood pressures, and waist circumferences and ratio. Also, both the normal and obese weight groups had comparable heart rate responses during both exercise protocols, producing a similar relative exercise intensity and effort between groups. Therefore, the brain-derived neurotrophic factor response was likely not influenced by disparities between aerobic fitness, with a greater level in obese subjects than normal weight subjects following acute high intensity interval exercise vs. continuous moderate intensity exercise.

Also, both the fat and typical weight bunches had equivalent pulse reactions amid both exercise conventions, delivering a comparable relative exercise power and exertion between gatherings.

Increased levels of cortisol have been shown to down regulate brain-derived neurotrophic factor expression; however, this relationship in response to exercise still remains equivocal. Specifically, our study and others did not observe any correlation between cortisol and brain-derived neurotrophic factor following either acute high-intensity exercise or continuous moderate-intensity exercise protocol, yet, the report of such is opposite.

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Contact details:
Alina Grace
Program Manager | Obesity Middle East 2019
Email id: obesityendo@mehealthevents.org