Decoding the secrets behind obesity: The interplay between genetics and environmental factors in body shaping

The causes of obesity are complex. Generally, obesity not caused by obvious endocrine or metabolic diseases is called simple obesity, accounting for 95% of all obese individuals. Obesity that develops after an underlying endocrine disorder is called secondary obesity, which is beyond the scope of this book. Some obese patients often say, "No weight loss method works for me; I'm naturally prone to obesity, I gain weight even from drinking water." This view suggests that whether or not someone will be obese is determined by genetics. Indeed, in reality, people with large appetites are not necessarily obese. Obesity is related to an individual's physical condition, which is influenced by genetic factors.

However, the above viewpoint represents a common misconception. Many people only emphasize the genetic factors that cause obesity, thus believing that obesity is unpredictable and incurable. In reality, genetic factors confer a susceptibility to obesity; that is, different people have varying sensitivities to external environmental conditions where energy intake exceeds expenditure (positive energy balance). When the external environment changes, such as overeating or reduced physical activity, weight gain is easy. However, if the external environment is not conducive to weight gain, such as food shortages or engaging in extremely strenuous physical labor daily, then even those with a genetic predisposition to obesity may not become obese. Therefore, obesity is caused by both genetic and environmental factors.

Genetic factors

(I) The Frugal Gene

The topic must be traced back to our ancestors. In ancient times, our ancestors had no guarantee of food. They would eat their fill when they found food, but if they went without food for several days, they would starve. This necessitated the ability to efficiently convert the energy from food into body fat for storage during periods of hunger. Throughout the long process of human evolution, only those who could endure prolonged hunger-those with the so-called "thrifty gene"-survived and reproduced, becoming the humans we know today. People with this gene type have a high capacity for storing body fat. Now, with improved living standards and easy access to abundant food, people readily convert excess energy into body fat for storage, leading to obesity.

(II) Research on Twins

Obesity has certain familial characteristics. Some studies indicate that if one parent is obese, their children have a 40% chance of being obese; if both parents are obese, the obesity rate can reach 70% to 80%. Many studies on genetic factors have used monozygotic twins as subjects. For example, to observe the influence of genetic factors on obesity development, several pairs of twin brothers are placed in the same environment, and each twin is given an extra 1000 kcal of energy per day. After several months, their body fat is measured.

The results showed that if one subject experienced a greater increase in body fat after consuming more food, their twin brother also experienced a greater increase in body fat when energy intake increased; conversely, if another subject experienced a smaller increase in body fat after increasing energy intake, their twin brother also experienced a smaller increase in body fat. In other words, the response to increased food intake was very consistent between twin pairs, but significantly different between other pairs of twins. This demonstrates that genetic factors do influence weight and body fat gain.

(III) The discovery of leptin

In 1950, Ingalls and several other researchers discovered a type of mouse with an excessive appetite and extreme obesity. The cause of their obesity was a mutation in a gene, which they named the obesity gene (ob gene). In late 1994, Zhang et al. cloned the obesity gene and discovered that leptin, the expression product of the obesity gene, controls the weight of mice. Subsequently, obesity genes in rats and humans were also cloned and mapped. The discovery of leptin led to a breakthrough in the genetic research of obesity.

Leptin is a protein hormone secreted by fat cells and composed of 167 amino acids. It controls body weight in animals and humans through two pathways: one is by transmitting signals of increased body fat to the satiety center in the hypothalamus, thereby controlling eating behavior, suppressing appetite, reducing food intake, and decreasing body fat accumulation; the other is by promoting thermogenesis in body fat tissue, increasing energy expenditure. Obesity gene defects are a cause of obesity. Injecting leptin into obese mice with congenital leptin deficiency and obese children significantly suppressed their appetite, promoted fat metabolism, and resulted in significant weight loss. The use of leptin to treat obesity in humans is still in the clinical trial stage.