TURDEP epidemiological studies found that the prevalence of obesity in the Turkish adult population increased from 22.3 percent to 31.2 percent from 1998 to 2010. According to this, it has been determined that obesity has increased by 34 percent in women and 107 percent in men in the last 12 years.
Among the reasons for the increase are the decrease in physical activity due to the easier life style in transportation, production and agriculture as a result of increasing technological development and the change in dietary habits in modern life. In this article, we will focus on the genetic factors that cause obesity and their effects on the disease.
What do genes have to do with obesity?
Obesity can be defined as an increase in body fat rate as a result of chronic energy imbalance in a person who consumes more calories as food than is necessary for the continuation of the body’s metabolic and physical functions.
The rapidly increasing prevalence of obesity in recent years is attributed to an “obesogenic” time and place that provides ready access to high-calorie foods but limits opportunities for physical activity. The obesity epidemic is more common in societies with these characteristics.
Obesity is an important public health problem because it increases the risk of developing diabetes, heart disease, stroke, cancer and other serious diseases.
Even in an obesogenic environment, not everyone is obese. Indirect scientific evidence from studies of obese family members, twins, and adopters before genomic studies have demonstrated the importance of genetic factors in a minority of obesity. Hereditary factors contribute more to childhood obesity.
One gene or multiple?
Obesity rarely occurs in families with a clear single gene inheritance caused by a single gene. Among these, the most common gene is MC4R, which encodes the melanocortin 4 receptor. Changes that reduce the function of the MC4R contribute to the development of obesity in a minority (<5 percent) of obese individuals in various ethnic groups.
However, in most obese people, no single genetic cause can be identified. Since 2006, more than 50 genes associated with obesity have been identified in genome-wide studies, most of which have only minor effects in the occurrence of the disease in obese individuals. In most obesity patients, the problem is multifactorial, that is, the result of complex interactions between many genes and environmental factors such as inactivity, nutritional disorder, and other hormonal diseases.
How do genes control energy balance?
The human brain regulates food intake by responding to signals from adipose (adipose) tissue, pancreas and digestive system. These signals are transmitted by hormones and other small molecules such as leptin, insulin, and ghrelin. The brain coordinates these signals with other inputs and gives commands to the body in the form of instructions. These commands are either to eat more food and reduce energy use, or vice versa. Genes underlie the signals and responses that drive food intake, and small changes in these genes can affect nutrition and calorie balance. Some genes with obesity-related variants are shown in Table 1.
Table 1: Selected genes with obesity-associated variants
| Gene symbol | Gene name | Energy of core product role in balance |
| ADIPOQ | Adipocyte, C1q | Adiponectin produced by fat cells increases energy expenditure |
| FTO | Fat mass and obesity-associated gene | Stimulates food intake |
| LEP | Leptin | Produced by fat cells |
| LEPR | Leptin receptor | Suppresses appetite when bound to leptin |
| INSIG2 | Insulin stimulating gene-2 | Regulation of cholesterol and fatty acid synthesis |
| MC4R | Melanocortin 4 receptor | Stimulates appetite when bound to alpha melanocyte stimulating hormone |
| PCSK1 | Proprotein convertor subtilisin / cupcake type 1 | Regulates insulin biosynthesis |
| PPARG | Peroxisome proliferator-activating receptor gamma | Regulates the development of adipose tissue and stimulates lipid uptake |
Energy is important for life. The regulation of human energy is unfortunately regulated for survival and protection against weakening in possible energy needs, rather than controlling weight gain. To help explain this situation, the “thrifty genotype” hypothesis has been proposed. This can be described as the negative state of our ancestors when the same genes that helped them provide energy in the future while they were starving from time to time, brought us in the present (where there is plenty of food).
How can this information help with protection?
Public health studies for obesity prevention focus on strategies that promote healthy eating and physical activity. These strategies should be given training, for example, to raise awareness of healthy eating in public service settings and schools. Such strategies will lead to positive behavioral changes for many, increasing success in return.
Epigenetics and Obesity
Environmental exposures during critical periods of human development can cause permanent changes in the activity of that gene without altering the sequence of the gene itself. This situation is called the “epigenetic” effect, and measuring and determining these effects requires measuring the chemical changes of DNA, RNA or related proteins. Although it is reasonable to think that epigenetics changes the effects of nutrition on genes, especially in children, epidemiological studies showing this situation are still at an early stage.
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