Genetics of Obesity

In the largest study of it's kind to date, researchers have looked at why a few people manage to stay thin while others gain weight easily. They have discovered that the hereditary dice are loaded in favour of thin people and against those at the obese end of the spectrum.More than six in ten adults are overweight, and one in four adults is obese. By age five, almost one in four children is either obese or overweight. Excess weight increases the risk of related health problems including heart disease and type 2 diabetes.  

While it is well known that changes in our environment, for example, easy access to high-calorie foods and sedentary lifestyles, have driven the rise in obesity in recent years, there is considerable individual variation in weight inside a populace that shares the same environment. A few people seem able to eat what they like and remain thin. This has led a few people to characterise overweight people as lazy or lacking willpower.

The researchers examine why and how some people find it easier to stay thin than others. Studies of twins have demonstrated that variation in body weight is generally affected by our genes. To date studies have overwhelmingly focused on people who are overweight. Hundreds of genes have been discovered that increase the possibility of an individual being overweight and in some people faulty genes can cause severe obesity from a young age.

Our DNA contains of a sequence of molecules known as base pairs, represented by the letters A, C, G and T. Strings of these base pairs form genetic regions. Our genes provide the code for how our body functions and changes in the spelling.

The team found a few regular genetic variants already identified as playing a role in obesity. Moreover, they found new genetic regions involved in severe obesity and some involved in healthy thinness.

To see what impact these genes had on an individual’s weight, the specialists included the contribution of the different genetic variants to calculate a genetic risk score. As anticipated, we found that obese people had a higher genetic risk score than normal weight individuals, which contributes to their risk of being overweight. The genetic dice are loaded against them.  

Importantly, the team also showed that thin individuals, had a much lower hereditary risk score they had less genetic variants that we know increased an individual's chances of being overweight.

This examination shows for the first time that healthy individuals are commonly thin because they have a lower burden of genes that increase an individual's chances of being overweight and not because they are morally superior, as certain individuals like to suggest. It's easy to rush to judgement and criticise individuals for their weight, but the science shows that things are far more complex. We have far less power over our weight than we may wish to think.    

We already know that individuals can be thin for various reasons. A few individuals are just not that interested in food whereas others can eat what they like, but never put on weight. If we can find the genes that prevent them from putting on weight, we might most likely focus on those genes to discover new weight loss strategies and help individuals who do not have this advantage.

Contact details:

Alina Grace

Program Manager | Obesity Middle East 2019

Email Id: obesityendo@mehealthevents.org

Vitamin D supplements may promote weight reduction in obese children

Vitamin D supplements may promote weight loss and reduce risk factors for future heart and metabolic disease in obese and overweight children. The findings indicate that vitamin D is the simple supplementation may be part of an effective strategy to tackle childhood obesity and reduce the risk of serious health problems, such as heart disease, in adulthood.

Obesity in childhood and adolescence represents a major health problem worldwide, which leads to the development of expensive, debilitating and serious complications, including diabetes and heart disease, in later life. Vitamin D deficiency is stereotypically associated with impaired bone health, in recent years it has been increasingly linked with increased body fat accumulation and obesity, with the precise nature of this relationship currently under intense investigation by scientists. However, the effect of vitamin D supplementation on the health and weight of obese children and adolescents had not yet been investigated.

In this study, researchers assessed 232 obese children and adolescents over 1 year, with 117 randomly assigned to receive vitamin D supplementation, in accordance with the guidelines on treatment and prevention of deficiency. Levels of vitamin D, body fat, and blood markers of liver function and heart health were assessed at the start of the study and 12 months later. The study reported that children given vitamin D supplements had significantly lower BMI, body fat and improved cholesterol levels after a year of supplementation.

These findings suggest that simple vitamin D supplementation may reduce the risk of obese and overweight children developing serious heart and metabolic complications in later life.

The team now plan to investigate the effects of vitamin D supplementation on the health of obese children and adolescents that already have unhealthy conditions, such as high blood pressure, high cholesterol and high blood glucose all of which increase the risk of heart disease, stroke and diabetes.

Although these initial findings indicate that vitamin D could be used in the treatment of obesity, there remains a lack of evidence on the safety and long-term effects of supplementation, particularly if there is no vitamin D deficiency. However, if your child is obese or overweight I recommend that you consult your primary care physician for advice, and consider having their vitamin D levels tested.

Contact details:

Alina Grace

Program Manager | Obesity Middle East 2019

Email Id: obesityendo@mehealthevents.org

Endocrine cells in the brain impact the optimization of behavior

An individual exposed to stress can usually rapidly adapt the own behavior to the specific situation. Biochemical messenger substances in the brain play a central role in this rapid transformation process. We know that hormones additionally have a stress regulating function, but that their effects are more slowly apparent. Using a combination of optical and genetic techniques, the research team has had the capacity to show that corticotrophs, the cell populations that prompts the adrenal cortex and produce the stress hormones of the hypothalamic-pituitary-adrenal axis, will quickly impact avoidance behavior immediately after the onset of a stress situation. This insight could add to the development of effective treatments which will facilitate the management of acute stress induced reactions or may even have the capacity to mitigate acute stress associated conditions.

The human body is controlled by the hormonal system and the nervous system. The hypothalamus situated in the middle of the basis of the brain has a key role here providing the link between the body and the different regions of the brain similarly as directly and indirectly controlling a progression of essential physiological vegetative functions. In addition, it is the most important control organ of the human endocrine system, because it regulates when and how much of a hormone is produced. Both the hypothalamus and its production of hormone are also subject to the impacts of emotional stress. The pituitary gland is connected to the hypothalamus and together they form a single functional unit called the hypothalamic-pituitary-adrenal axis.

Hormones secreted by the hypothalamus incorporate the supposed releasing hormones, such as the corticotropin-releasing hormone. This stimulates the production of the adrenocorticotropic hormone in the pituitary gland. The adrenocorticotropic hormone is a hormone secreted by the anterior lobe of the pituitary and it regulates the production of other hormones, such as the stress hormone cortisol.

It can be basically assumed that the neurotransmitters of the CNS quickly determine whether fight or flight behavior is to develop in a given situation. To date, medical science has conjectured that the stress-regulating effects of the hormones of the HPA axis come into play far more slowly. Stress researchers found it very problematic to establish the concrete role of the hypothalamic-pituitary-adrenal axis in the rapid adaptation of behavior in a stress situation in more detail in standard animal models. This is because the location of the pituitary gland and hypothalamus in mammals makes them difficult to access. To overcome these obstacles, the researcher decided to create an innovative optogenetic research technique. They managed to develop a hereditarily modified zebrafish larva in which they had the capacity to manipulate the activity of the HPA axis using light and subsequently observe the resultant changes to the responses of the altered cells.  

The researchers introduced a synthetic enzyme into their animal model that elevates the levels of the intracellular messenger substance cyclic adenosine monophosphate (cAMP) only in the corticotropic cells of the hypothalamic-pituitary-adrenal axis. Their rise is important for the release of hormones in the corticotropic cells of the anterior pituitary. The levels of the resulting so-called transgenetic animal stress hormones can be increased by means of exposure to light. This means the researchers can thus observe the accompanying changes to behavior.

The recently published research results that the corticotropic cells in the pituitary become directly active on the beginning of a stress situation that is seen as distressing. These then influence locomotion and avoidance behavior as well as the sensitivity to the stimulus. The specialists translate this as proof that the corticotropic cells in the pituitary play a significant role in the rapid adaptation of behavior to local environments identified as antagonistic.   

Contact details:

Alina Grace

Program Manager | Obesity Middle East 2019

Email Id: obesityendo@mehealthevents.org

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.

For more details, please visit Obesity Middle East 2019

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

Fatness versus fitness: which matters more?

Numerous studies have looked at fitness and obesity as two separate elements because they are apparently separate ideas: one measures how well your lungs and heart work to supply oxygen to your muscles while the other is a proportion of your body height and weight. However, the measures of fitness and fatness are both influenced by how much you weigh.

Likewise, what researchers mean by fatness is really body mass index (BMI), a measure of body fat based on height and weight. Strictly speaking, obesity doesn’t mean you are automatically unfit. There are fat people who run every day, and then there are thin people who couldn’t run a mile for their life. A muscular individual can also be considered obese, because muscle weighs over fat, and be very fit.

But these are exceptions, not the rule. Studies demonstrate that when someone is considered as obese, the probability of them being fit is very low. So in our society, being fat still generally means lower fitness.

Fatness makes it harder to enhance fitness

For people who are obese, concentrating on losing weight is a better place to start than just focusing on fitness. That is as a result of extra weight can make it harder to move, and thus harder to exercise. Obese people typically have a difficult time doing physical activity due to limited mobility, body size and joint pain.

Physiologically, it’s harder for an obese individual to do the same amount of exercise as a healthy weight individual because of the extra weight they carry. Heavier individuals need more oxygen to do the same exercise as a healthy weight person. Some obese individuals report that even walking can seem difficult. Fitness is just harder to achieve if you can’t move effectively.

Fatness reduces the quality of life

The debate around fitness and fatness centres on studies that show that compared to normal weight-fit individuals, unfit individuals had twice the risk of mortality regardless of BMI. But as these studies show, a relatively small proportion of people are fit and obese.

But mortality is not the only issue. Obesity has been shown to predict heart disease, liver disease, diabetes and a whole host of health problems that will need taking daily pills or having daily injections or result in invasive procedures. Even if a higher BMI does not predict earlier death, this doesn’t mean that it doesn’t matter to your health.

Increasing physical activity while not losing weight won't probably improve these patients’ lives. To enhance their health and quality of life, it is important to exercise every day, eat healthy food and most importantly lose some weight.

Endocrine disorder is most common cause of elevated calcium levels

Unusually high calcium levels in the blood can quite often be followed to essential hyperparathyroidism, an undertreated, underreported condition that influences predominantly women and the elderly, according to a new study by researchers.

The condition, which results from overactive parathyroid glands and includes symptoms of bone loss, depression and fatigue that may go undetected for years, is most often seen in women over the age of 50, the researchers discovered.

The four parathyroid glands, which are situated in the neck, next to the thyroid, control the body's calcium levels. When one is dysfunctional, it can cause major imbalances - for example, by releasing calcium from the bones and into the circulatory system. Over time, calcium loss from bones often prompts to osteoporosis and fractures, and excessive calcium levels in the blood can cause kidney stones and worsening kidney function. 

The researchers determined that hyperparathyroidism is the leading cause of high blood-calcium levels and is responsible for nearly 90 percent of all cases. The findings suggest that hyperparathyroidism is the predominant reason for high calcium levels, so if patients discover they have high calcium, they should also have their parathyroid hormone level checked. Hyperparathyroidism, which influences approximately 1 percent of the population, can be identified by measuring parathyroid hormone levels to determine if they are elevated or abnormal. 

The researchers noted that the growing prevalence is likely due to increased calcium testing, annual lab tests to monitor patients with indications and the low rate of surgery to treat the disorder. Previous studies have shown that only 28% of patients with hyperparathyroidism undergo surgery to remove the overactive parathyroid gland - the most reliable way to correct the disorder. Women can suffer over years with hyperparathyroidism and not know they have it, which is especially critical in midlife when bone health is so critical. Appropriate management of the disorder is essential. Surgery should be considered in most of the individuals with primary hyperparathyroidism.  

The scientists noticed that the developing pervasiveness is likely because of expanded calcium testing, yearly lab tests to screen patients with indications and the low rate of medical procedure to treat the confusion. Past research has appeared just 28 percent of patients with hyperparathyroidism experience medical procedure to expel the overactive parathyroid organ - the most solid approach to address the turmoil. Ladies can languish over years with hyperparathyroidism and not realize they have it, which is particularly basic in midlife when bone wellbeing is so critical. Suitable administration of the turmoil is fundamental. Medical procedure ought to be considered in most of the individuals with essential hyperparathyroidism.

The next step, the researcher said that further study of this patient population to examine the long-term impact of the condition on bone health and the effectiveness of different management strategies on outcomes.

For more details, please visit Obesity Middle East 2019

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