Daily energy expenditure rests on three components: basal metabolic rate (BMR), which accounts for 60-75% and represents calories burned at rest for vital functions, calculated by the Harris-Benedict equation factoring age, sex, weight, and height; diet-induced thermogenesis (DIT) or the thermic effect of food, representing energy used to digest and process nutrients and highest for protein at 20-30%, followed by carbohydrates (5-10%) and fats (0-3%); and physical activity. A high-protein diet can therefore raise 24-hour expenditure by 50-100 kcal/day. Understanding the energy density of foods (alcohol 7 kcal/g, fat 9 kcal/g, carbs and protein 4 kcal/g, fiber around 2 kcal/g) explains why high-fat foods like oils, butter, and nuts deliver more calories per gram than fruits and vegetables. Energy balance compares calories in versus out and determines weight change, while macronutrient balance, the relative proportions of protein, carbs, and fat, influences metabolic health, hormones, and body composition independent of total calories.
Body weight regulation hinges on the distinction between hunger, the physiological drive from ghrelin, glucose, and gastric signals, and appetite, the psychological desire shaped by sight, smell, memory, stress, and social cues. Satiation ends a meal via gastric distension and gut hormones like CCK and GLP-1, whereas satiety suppresses hunger between meals; high-volume, high-protein, high-fiber foods boost both, while hyperpalatable foods undermine satiation. Leptin, secreted by adipocytes in proportion to fat stores, normally signals satiety to the hypothalamus, but in obesity leptin resistance develops so that high circulating levels fail to suppress appetite. The endocannabinoid system, via CB1 receptors, modulates hedonic appetite, which explains why CB1 antagonists like rimonabant produced depression as a side effect, and why THC triggers the so-called munchies for sweet and fatty foods. The protein leverage hypothesis proposes that humans prioritize a fixed absolute protein intake (around 15-20% of energy) and overeat carbs and fats when protein is diluted by processed foods, potentially driving obesity.
Body composition matters as much as weight: brown adipose tissue generates heat via uncoupling protein 1 (UCP1) and can be activated by cold, capsaicin, and catechins, while white adipose tissue stores triglycerides; beige adipocytes can be induced in white fat by exercise and certain foods. Sarcopenic obesity, the combination of low muscle mass and high adiposity common in older adults, requires resistance training paired with adequate protein (1.2-1.5 g/kg/day), vitamin D, and modest calorie restriction to preserve lean mass. At the hormonal level, fasting insulin and the HOMA-IR index estimate insulin resistance; values above roughly 1.9-2.5 suggest metabolic dysfunction that can be improved by weight loss, low-GI eating, exercise, and sleep before type 2 diabetes develops, characterized by chronically elevated glucose and HbA1c at or above 6.5%. Lipid assessment has also evolved: LDL-C measures cholesterol mass inside LDL particles, LDL-P counts particle number, apoB counts all atherogenic particles, and non-HDL cholesterol (total minus HDL) better captures risk in metabolic syndrome and diabetes. HDL itself varies, with larger HDL2 particles being more efficient at reverse cholesterol transport than smaller HDL3 particles, though simply raising HDL-C with drugs has not consistently lowered cardiovascular events.