bubble_chart Overview

Obesity is a common and ancient metabolic syndrome. When the caloric intake of the human body exceeds the caloric expenditure, the excess calories are stored in the body as fat. When the amount of fat exceeds the normal physiological requirement and reaches a certain value, it evolves into obesity. In normal adult males, adipose tissue accounts for about 15-18% of body weight, and in females, it accounts for about 20-25%. With age, the proportion of body fat increases accordingly. Obesity is defined as a condition where body weight exceeds the standard weight by 20% or the body mass index (BMI = weight (Kg) / (height) ² (m²)) is greater than 24. If there is no obvious disease cause, it is called simple obesity; if there is a clear disease cause, it is called secondary obesity.

bubble_chart Etiology

The increase in fat synthesis due to higher caloric intake than expenditure is the material basis of obesity.

(1) Internal Causes: Intrinsic factors within the human body that cause fat metabolism disorders leading to obesity.

1. Genetic Factors

The onset of simple obesity in humans has a certain genetic background. Mayer et al. reported that if one parent is obese, the obesity rate of their children is about 50%; if both parents are obese, the obesity rate of their children rises to 80%.

Human obesity is generally considered to be polygenic, with genetics playing a predisposing role in its onset. The formation of obesity is also related to the interaction of lifestyle behaviors, eating habits, preferences, insulin response, and socio-psychological factors.

2. Neuropsychological Factors

It is known that there are two pairs of nuclei in the hypothalamus of humans and various animals related to eating behavior. One pair is the ventromedial nucleus (VMH), also known as the satiety center; the other is the lateral hypothalamic area (LHA), also known as the hunger center. When the satiety center is excited, there is a feeling of fullness and refusal to eat; when it is damaged, appetite greatly increases. When the hunger center is excited, appetite is vigorous; when it is damaged, anorexia and refusal to eat occur. The two regulate and constrain each other, maintaining a dynamic balance under physiological conditions, regulating appetite within a normal range to maintain normal body weight. When the hypothalamus is diseased, whether due to sequelae of inflammation (such as meningitis, encephalitis), trauma, tumors, and other pathological changes, if the ventromedial nucleus is damaged, the function of the lateral hypothalamic area becomes relatively hyperactive, leading to insatiable eating and obesity. Conversely, if the lateral hypothalamic area is damaged, the ventromedial nucleus becomes relatively hyperactive, leading to anorexia and weight loss. Additionally, this area has close anatomical connections with higher neural tissues, which can also regulate the feeding center to some extent. The blood-brain barrier in the hypothalamus is relatively weak, making it easier for various bioactive factors in the blood to migrate there, thus affecting eating behavior. These factors include glucose, free fatty acids, norepinephrine, dopamine, serotonin, insulin, etc. Moreover, psychological factors often affect appetite; the function of the feeding center is influenced by mental state. When the mind is overly tense and the sympathetic nervous system is excited or adrenergic nerves are stimulated (especially when α-receptors dominate), appetite is suppressed; when the vagus nerve is excited and insulin secretion increases, appetite often becomes hyperactive. The ventromedial nucleus is the sympathetic center, and the lateral hypothalamic area is the parasympathetic center, both playing important roles in the pathogenesis of this condition.

3. Hyperinsulinemia

In recent years, the role of hyperinsulinemia in the pathogenesis of obesity has attracted attention. Obesity often coexists with hyperinsulinemia, but it is generally believed that hyperinsulinemia causes obesity. The insulin release in hyperinsulinemic obese individuals is about three times that of normal people.

Insulin has a significant effect on promoting fat accumulation. Some believe that insulin can serve as an indicator of total body fat and, to some extent, as a monitoring factor for obesity. Others believe that plasma insulin concentration is significantly positively correlated with total body fat.

4. Abnormal Brown Adipose Tissue

Brown adipose tissue is a type of fat tissue discovered only in recent years, corresponding to white adipose tissue mainly distributed subcutaneously and around internal organs. Brown adipose tissue has a limited distribution, only found between the shoulder blades, the back of the neck, the armpits, the mediastinum, and around the kidneys. Its tissue appearance is light brown, and the cell volume changes relatively little.

White adipose tissue is a form of energy storage; the body stores excess energy in the form of neutral fats, which are hydrolyzed in fat cells when energy is needed. The volume of white fat cells varies significantly with energy release and storage.

Brown adipose tissue functionally serves as a thermogenic organ, meaning that when the body consumes food or is stimulated by cold, the fat within brown fat cells burns, thereby determining the body's energy metabolism level. These two scenarios are respectively referred to as diet-induced thermogenesis and cold-induced thermogenesis.

Of course, the function of this special protein is influenced by various factors. It can be seen that brown adipose tissue, a thermogenic tissue, directly participates in the overall regulation of body heat, dissipating excess heat from the body, thereby balancing the body's energy metabolism.

5. Others

Overeating can stimulate the small intestine to produce excessive gastric inhibitory peptide (GIP), which stimulates pancreatic β-cells to release insulin. In cases of pituitary hypofunction, especially with reduced growth hormone, gonadotropin, and thyroid-stimulating hormone, leading to hypogonadism and hypothyroidism, a special type of obesity may occur, possibly related to reduced fat mobilization and relatively increased synthesis. Clinically, obesity is more common in women, especially in multiparous women, those in menopause, or those taking oral female contraceptives, suggesting that estrogen is related to fat anabolism. In cases of adrenal cortical hyperfunction, increased cortisol secretion promotes gluconeogenesis, raises blood sugar, stimulates increased insulin secretion, thereby increasing fat synthesis, while cortisol promotes fat breakdown.

(II) External Causes Mainly due to excessive diet and insufficient activity.

When the daily caloric intake exceeds the energy required for consumption, in addition to being stored in the form of liver and muscle glycogen, it is almost entirely converted into fat and stored in the body's fat depots, mainly as triglycerides. Since glycogen storage is limited, fat becomes the main form of energy storage in the human body. Regular intake of excessive neutral fats and carbohydrates accelerates fat synthesis, becoming an external cause of obesity, often occurring in situations of reduced activity, such as stopping physical exercise, reducing physical labor, or during the convalescence stage of illness, bed rest, postpartum recovery, etc.

bubble_chart Clinical Manifestations

The clinical manifestations of obesity vary depending on the disease cause. Secondary obesity, in addition to obesity, presents with the primary disease syndrome. Below, we focus on simple obesity. This group of conditions can occur at any age, with juvenile obesity starting from childhood; adult-onset obesity often begins between 20 to 25 years of age; however, clinically, it is more common among middle-aged women aged 40 to 50, and is also not uncommon among the elderly aged 60 to 70 and above. In males, fat distribution is mainly in the neck, trunk, and head, while in females, it is primarily in the abdomen, lower abdomen, chest, breasts, and buttocks; grade I obesity often presents without symptoms, while grade III obesity may exhibit the following syndromes:

(1) Alveolar Hypoventilation Syndrome

This syndrome is also known as Pick-wickian syndrome. Due to the accumulation of a large amount of fat in the body, excessive weight gain, and the need to consume energy during activity, oxygen consumption also increases. Therefore, obese individuals generally dislike exercise, are less active and prone to sleepiness, and easily feel fatigued after slight activity or physical labor. The total oxygen uptake of obese individuals increases, but when calculated per unit of body surface area, it is lower than normal. When there is a significant amount of fat in the chest and abdomen, the abdominal wall thickens, the diaphragm is elevated, and ventilation becomes difficult, leading to CO₂ retention. PCO₂ often exceeds 6.3 kPa (48 mmHg), with the normal being 5.3 kPa (40 mmHg), resulting in hypoxia, causing shortness of breath, and even secondary polycythemia, pulmonary stirred pulse hypertension, leading to chronic lung heart disease and heart failure, which can recover after weight loss. Due to the tendency towards hypoxia and CO₂ retention, patients often appear lethargic and drowsy, known as Pick-wickian syndrome.

(2) Cardiovascular Syndrome

Grade III obesity may be due to increased blood vessels in adipose tissue, leading to increased effective circulating blood volume, cardiac output, and heart burden, sometimes accompanied by hypertension and stirred pulse atherosclerosis, further increasing the heart burden, causing left ventricular hypertrophy. At the same time, fat deposition inside and outside the myocardium makes it more prone to myocardial strain, leading to left heart enlargement and left heart failure. Combined with the aforementioned alveolar hypoventilation syndrome, sudden death may occasionally occur.

(3) Endocrine and Metabolic Disorders

Fasting and postprandial plasma insulin levels are elevated, with baseline values reaching 30 μu/ml and postprandial values reaching 300 μu/ml, about double that of normal individuals. Patients have hyperinsulinemia, increased C-peptide secretion, and insulin resistance, leading to impaired glucose tolerance or diabetes. Total lipids, cholesterol, triglycerides, and free fatty acids are often elevated, resulting in hyperlipidemia and hyperlipoproteinemia, forming the basis for stirred pulse atherosclerosis, coronary heart disease, and gallstones. Plasma total protein, albumin, and globulin in obese individuals are usually within the normal range, but certain amino acids may increase, such as arginine, leucine, isoleucine, tyrosine, and phenylalanine. Thus, the increase in blood sugar and plasma amino acids forms a vicious cycle stimulating pancreatic β-cells, thereby worsening obesity. Thyroid function is generally normal, with T₃ increasing during overeating, and growth hormone (GH) secretion being sluggish.

(4) Digestive System Syndrome

Increased appetite, frequent hunger, and overeating, constipation, abdominal distension, and fullness are common. Obese individuals may have varying degrees of hepatic steatosis and enlargement, and those with gallstones may have a history of chronic indigestion and biliary colicky pain.

(5) Others

Obese individuals have abnormal purine metabolism, increased plasma uric acid, making the incidence of pain wind significantly higher than normal individuals, and those with coronary heart disease may have a history of heart colicky pain. Patients may have light purple or white striae on the skin, distributed on the outer buttocks, inner thighs, knees, and lower abdomen, where folds are prone to wear, causing dermatitis and skin fungus. They often sweat excessively, fear heat, have lower resistance, and are prone to infections.

bubble_chart Diagnosis

Diagnosis can be made based on signs and body weight. First, the standard body weight must be determined according to the patient's age and height (refer to the human standard body weight table), or calculated using the following formula: Standard body weight (kg) = [Height (cm) - 100] × 0.9. If the patient's actual body weight exceeds the standard body weight by 20%, obesity can be diagnosed, but factors such as muscle development or water retention must be excluded. Clinically, in addition to signs and body weight, the following methods can be used for diagnosis:

1. Skinfold caliper measurement of subcutaneous fat thickness. Common measurement sites for human fat include the triceps skinfold thickness and the subscapular skinfold thickness. For adults, if the sum of these two measurements is ≥4cm for males and ≥5cm for females, obesity can be diagnosed. Measurements from multiple sites can provide more reliable results.

2. X-ray estimation of subcutaneous fat thickness.

3. Calculation based on height and weight using the Body Mass Index (BMI) (weight (kg) / height ² (m²)). A BMI >24 indicates obesity.

bubble_chart Treatment Measures

Preventing obesity is more effective and important than treating it. Especially for those with a family history of obesity, women postpartum and during menopause, men over middle age, or those in the stage of convalescence after illness, preventing obesity is crucial. The methods include appropriately controlling food intake, avoiding high-sugar, high-fat, and high-calorie diets; regularly engaging in physical labor and exercise (those in the stage of convalescence should do so under the guidance of a physician).

The treatment of obesity primarily involves controlling diet and increasing physical activity, and should not rely solely on medication. Long-term medication use inevitably leads to side effects and may not sustain effectiveness.

For those with grade I obesity, it is only necessary to limit fats, sugary pastries, beer, etc., so that the total daily calorie intake is lower than the consumption. Engaging in more physical labor and exercise, such as reducing weight by 500-1000g per month to gradually reach the normal standard weight, does not require medication.

For those with grade II or higher obesity, stricter control of total calorie intake is necessary. Female patients are advised to limit their food intake to 5-6.3MJ (1200-1500kcal) per day; exceeding 6.3MJ per day is ineffective. Men should control their intake to 6.3-7.6MJ (1500-1800kcal) per day, aiming to lose 1-2 pounds per week at this standard. The diet should ensure an appropriate amount of animal protein containing essential amino acids (about one-third of the total protein is suitable), with a protein intake of no less than 1g per kilogram of body weight per day. Fat intake should be strictly limited, and sodium intake should also be restricted to prevent water and sodium retention during weight loss, which also benefits blood pressure reduction and appetite suppression. Additionally, limit sweets, beer, etc., as mentioned before. If weight cannot be reduced after several weeks of dietary control, the total daily calorie intake can be reduced to 3.4-5MJ (800-1200kcal) per day, but too few calories can lead to fatigue, weakness, fear of cold, lack of strength, and mental sluggishness, requiring close observation. Research shows that in the early stages of dietary treatment, protein consumption is higher, leading to faster weight loss and negative nitrogen balance. When a low-calorie diet is maintained, a protective nitrogen retention reaction occurs, gradually restoring nitrogen balance, thus increasing fat consumption. However, since fat produces about ten times more calories than protein, the amount of fat tissue lost is significantly less than protein tissue. When protein antagonism synthesis increases, it may cause weight to rebound, which is the body's regulatory process after calorie restriction. Therefore, dietary treatment often shows limited effectiveness, and in such cases, encouraging exercise therapy to increase calorie consumption is advisable.

When dietary and exercise therapies are ineffective, drug-assisted treatment can be considered. Drugs are mainly divided into six categories: 1. Appetite suppressants—central appetite suppressants, peptide hormones, short-chain organic acids; 2. Digestion and absorption inhibitors—carbohydrate absorption inhibitors, lipid absorption inhibitors; 3. Fat synthesis inhibitors; 4. Insulin secretion inhibitors; 5. Metabolic stimulants; 6. Fat cell proliferation inhibitors.

Some of the above categories of drugs are already quite mature, while others are still in the research and development stage. Commonly used drugs include amphetamine, fenfluramine, and clobenzorex.

bubble_chart Differentiation

After the diagnosis of obesity is confirmed, a combination of medical history, physical examination, and laboratory data can be used to differentiate between simple and secondary obesity. If accompanied by hypertension, central obesity, purple striae, amenorrhea, and elevated 24-hour urinary 17-hydroxycorticosteroids, Cushing's syndrome should be considered. If the metabolic rate is low, further thyroid function tests such as T₃, T₄, and TSH should be conducted. Additionally, attention should be paid to the presence of accompanying conditions such as diabetes, coronary heart disease, atherosclerosis, angina, and gallstones.