Biological pathways to active weight loss: from accelerated capsaicin metabolism to appetite suppression by ovomucoid.

Weight-loss foods have flooded society. However, almost all of these are made from low-calorie ingredients, masking hunger with a feeling of fullness-making them, in essence, passive weight-loss foods. Research is now underway on more active weight-loss foods, such as those that accelerate energy expenditure, those that inhibit digestive enzymes without producing calories, appetite suppressants, and undigested mixed fats. Everyone knows that the spiciness of chili peppers and black pepper stimulates the tongue and stomach, increasing appetite.

Recently, the role of capsaicin, the pungent component in chili pepper skin, has attracted attention. According to research by Professor Kazuo Iwanaka and colleagues at Kyoto University, mice fed a diet supplemented with capsaicin accumulated less fat and gained less weight than mice fed a normal diet. This is because absorbed capsaicin stimulates the central nervous system via the bloodstream, promoting the secretion of adrenaline and noradrenaline from the adrenal cortex through the sympathetic nervous system, resulting in accelerated fat breakdown. Similar to physical exercise, capsaicin also promotes energy metabolism.

Many people have experienced feeling warm and sweating after eating chili peppers, and feeling less cold in winter, indicating that it promotes energy metabolism. If the safety of this energy-boosting substance can be confirmed, it could potentially be used for weight loss. Taisho Pharmaceutical Co., Ltd. has already applied this principle to develop a weight-loss food product made from red chili peppers, marketed under the brand name "Red Protein." This is a rare weight-loss food for overweight people who enjoy spicy food.

Ordinary fat cells, commonly known as fat, are called white fat cells because they are white in color. Brown fat cells, as the name suggests, are brown. White fat cells are found throughout the body and are numerous, while brown fat cells are generally distributed only in limited areas such as the head to the back, armpits, and around the kidneys, and are also fewer in number. White fat cells can store excess energy, while brown fat cells do not store fat; their function is only to break it down to generate heat. However, this heat generation only occurs after meals and when feeling cold.

Researchers have found that mice with a predisposition to obesity have less brown adipose tissue than normal mice. Overeating and lack of exercise are both causes of obesity. Recently, poor function of brown adipose tissue has been identified as a third important cause and has received particular attention. Brown adipose tissue is thermogenic tissue. After eating, it generates heat by expending energy, thus preventing weight gain. Therefore, the function of brown adipose tissue is exactly the opposite of that of white adipose tissue, which stores energy.

Experiments conducted by Toshihide Yoshida and colleagues at the First Department of Internal Medicine, Kyoto Prefectural University of Medicine, demonstrated that feeding mice that tend to gain weight even with minimal food intake with a novel weight-loss drug developed in the UK resulted in a weight loss of approximately 25% within two weeks, bringing them to an average weight. This novel weight-loss drug, developed by the British Medical Research Institute in 1983, is a sympathetic nervous system stimulant and marketed under the brand name "BRL26830A." This drug enhances the function of brown adipose tissue, which breaks down fat to generate heat.

This drug only breaks down excess body fat, thus attracting particular attention from women struggling to lose weight. However, this weight-loss drug is still in the experimental stage in the UK. According to Toshihide Yoshida, there are clinical reports in the UK that this drug can reduce weight by 9 kilograms, but the relationship between obesity and brown adipose tissue is not yet fully understood. Before using it as a weight-loss drug, it is necessary to first determine whether it can be used to treat diabetes that coexists with obesity. Toshihide Yoshida and others conducting research on obesity control are using tobacco, which is said to have weight-loss effects, to study the effects on brown adipose tissue.

A specialized smoking device was created, and experiments were first conducted on mice. They found that mice placed in the device and allowed to smoke weighed significantly less than mice placed in the device but not allowed to smoke, and mice not placed in the device at all, thus confirming the anti-obesity effect of tobacco. Next, they experimented with mice with impaired brown adipose tissue function, which would become obese even without increased feed intake. They allowed these mice to smoke three "Mild Seven" brand cigarettes daily. After two weeks, the fat from the obese mice was collected for analysis.

They found that its thermogenic activity increased by about three times, and the rate of consumption of hormones that transmit brain signals to brown adipose tissue was about five times faster. Based on this, they concluded that "cigarettes stimulate the central nervous system, thereby affecting brown adipose tissue and resulting in weight loss." Subsequently, they administered nicotine subcutaneously to obese mice for two consecutive weeks, obtaining almost identical results, confirming that nicotine is the component that inhibits obesity. While there are several reasons why smoking can inhibit obesity,...

While it may reduce food intake by impairing taste and digestion, and promote overall metabolism, its direct mechanism of action remains unclear. Yoshida Toshihide believes that humans have the same structure, but because smoking is harmful, he discourages smoking and aims to develop harmless drugs to suppress obesity. The research team believes that among the approximately 4,000 chemical substances contained in tobacco, besides the harmful nicotine, there may be harmless substances that suppress obesity, and therefore plans to continue research.

A research team at Kyoto University has demonstrated in animal experiments using mice that a protein called ovomucoid, found in egg white, can suppress appetite. Ovomucin accounts for 12%–13% of the protein in egg white and is a glycoprotein with a molecular weight of 28,000. Feeding mice with ovomucoid reduced their food intake by 30%, suggesting its potential as a novel anti-obesity drug. The research team plans to conduct clinical trials at Kyoto University to determine its effects on humans. The team also conducted experiments with mice that had fasted for six hours.

The results showed that 20 mice fed a diet mixed with ovomucoid consumed an average of only 4.4 grams of food one hour later, while the same 20 mice fed a diet without ovomucoid consumed an average of 5.9 grams. After an animal eats, its pancreas secretes trypsin, a digestive enzyme that breaks down proteins. Trypsin produces a feeling of fullness, thus preventing overeating. When eating in the morning, the digestive enzymes are not fully secreted, so the feeling of fullness appears later, often leading to overeating and contributing to obesity.

Experimental results showed that adding ovomucoid to the diet of mice increased the concentration of cholecystokinin (CCK), a hormone that promotes trypsin secretion, in the blood-to four times higher than in mice without ovomucoid. Therefore, mice fed with ovomucoid-added diets quickly felt full, thus reducing their food intake. If ovomucoid had the same effect on humans, it could be calculated that a 46 kg person could reduce their daily food intake by approximately 400 grams. The research team believes that whether the same effect applies to humans needs to be confirmed through experiments. Given that ovomucoid is a component of eggs, it can be considered safe.