Human energy metabolism and the metabolic characteristics of obesity

Human energy expenditure is mainly composed of basal metabolism (65%–70%), physical activity (15%–30%), and the thermic effect of food (10%). Basal metabolism is the minimum energy expenditure required to maintain life. Lean body mass (fat-free mass) is the core factor affecting basal metabolism, and the two are positively correlated. Basal metabolic rate (BMR) is also affected by sex, age, thyroid hormone levels, and ambient temperature. The thermic effect of food (TEF) refers to the extra energy expenditure resulting from food intake; the thermic effect of protein is the highest, reaching up to 30%. Energy expenditure from physical activity is the part with the greatest individual variation.

Among energy measurement methods, direct calorimetry is mostly used in research due to the high cost of equipment. Indirect calorimetry (gas metabolism method) is the most widely used in clinical practice, calculating energy consumption based on the constant ratio of oxygen consumption to carbon dioxide production. The double-standardized water method is the gold standard for determining energy requirements, but its high cost and demanding technology limit its practical application. The commonly used Harris-Benedict formula in clinical practice is as follows: Male basal metabolic rate = 66 + 13.7 × weight (kg) + 5.0 × height (cm) - 6.8 × age (years); Female basal metabolic rate = 655 + 9.5 × weight (kg) + 1.8 × height (cm) - 4.7 × age (years). This formula may overestimate by 7% to 27% in obese individuals; therefore, it is recommended to use the Katch-McArdle formula based on lean body mass: BMR = 370 + 21.6 × lean body mass (kg).

Obese individuals exhibit unique characteristics in their energy metabolism. While some pathological obesity (such as hypothyroidism) is attributed to low body mass index (BMR), the main drivers of physiological obesity are excessive intake and insufficient physical activity. In fact, due to their larger absolute weight and lean body mass, obese individuals typically have higher BMR measurements than those of normal weight. Exercise not only directly increases energy expenditure but also enhances BMR by increasing muscle mass. Consistently performing 200-300 minutes of moderate-intensity aerobic exercise per week can significantly improve metabolism.

In terms of carbohydrate metabolism, the most prominent characteristic of obese individuals is insulin resistance (IR). IR is often accompanied by increased abdominal fat, leading to decreased receptor affinity or defects in the insulin signaling cascade. IR in skeletal muscle is a typical feature of obesity and also the earliest characteristic of type 2 diabetes. In an IR state, skeletal muscle's oxidative clearance of glucose is impaired, while adipose tissue and the liver increase glucose uptake, inducing lipid synthesis. Furthermore, obese individuals often have persistent hyperinsulinemia, which promotes hepatic fat synthesis, increases the secretion of very low-density lipoprotein (VLDL), and elevates triglycerides (TG).

Lipid metabolism also undergoes pathological changes in obesity. This manifests as lipid metabolism disorders, with reduced mobilization and utilization of free fatty acids (FFA) by tissues, leading to a general increase in plasma FFA, cholesterol, and triglycerides (TG). For every 10% increase in body weight, plasma cholesterol increases by 0.3 mmol/L. Its dyslipidemia characteristics include elevated FFA and TG, decreased high-density lipoprotein cholesterol (HDL-c), and altered low-density lipoprotein cholesterol (LDL-c) properties. This metabolic background highly predisposes to non-alcoholic fatty liver disease (NAFLD).

Adipose tissue grows through hypertrophy (increased cell size) and proliferation (increased number). In adults, adipocyte size is positively correlated with hyperinsulinemia. Furthermore, deficiencies in enzymes such as lipoprotein lipase (LPL) play a crucial role in obesity. LPL controls the entry of exogenous fatty acids into cells. Obese individuals have low LPL activity in skeletal muscle, leading to reduced fatty acid oxidation, which promotes the transfer and storage of fat in tissues, forming a pathological circuit involving energy balance, material transformation, and enzymatic deficiencies.