Gut endocrine regulation and energy consumption: from gut microbiota feedback to human metabolic assessment

3. Neuroendocrine Mechanisms Involving Gut Microbiota: Gut microbiota can bidirectionally regulate the brain through neuroendocrine pathways, thereby influencing the host's food intake. In a balanced state, gut microbiota can regulate the secretion of intestinal peptides, such as cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), gastrin (OXM), and pyrotypin (PYY), which are appetite-suppressing hormones. These hormones can act on the arcuate nucleus of the hypothalamus to inhibit neuropeptide Y (NPY)/AgRP, activating hypothalamic neurons and stimulating the brain to produce a feeling of satiety. However, once the gut microbiota is imbalanced, the number of secreted intestinal peptides decreases, failing to stimulate the hypothalamus to produce a feeling of satiety, leading to excessive energy intake and obesity. Gut microbiota can ferment undigested carbohydrates and proteins in the host into SCFAs (saturated fatty acids, fatty acids, and fatty acids). Besides serving as an energy source (accounting for approximately 10% of the body's energy absorption), SCFAs can also activate G protein-coupled receptors GPR41 and GPR43 on the intestinal surface, promoting the secretion of GLP-1 and PYY. GLP-1, by stimulating insulin secretion from pancreatic β-cells and reducing glucagon secretion, simultaneously acts on the central nervous system, inducing a feeling of satiety and suppressing appetite. PYY reduces intestinal motility, prolongs food intake time, and enhances satiety, thereby reducing food consumption. Therefore, supplementing with dietary fiber to increase the amount of short-chain fatty acids in the cecum and raise plasma PYY and GLP-1 levels can increase satiety, reduce energy intake, and thus alleviate obesity. Simultaneously, SCFAs bind to GPR43 on the surface of intestinal L cells, activating Treg cells, upregulating the expression of Foxp3 and IL-10, and thus inhibiting inflammatory responses. They also improve intestinal permeability by downregulating the endocannabinoid system, reducing plasma LPS levels, maintaining gut microbiota and energy homeostasis, and improving metabolism. Studies have indicated that acetate produced in the gut after consuming high-calorie foods is a key factor leading to obesity. Acetate can cross the blood-brain barrier via the bloodstream, entering the brain and central nervous system, activating the parasympathetic nervous system, causing elevated blood glucose, inducing pancreatic β-cells to secrete large amounts of insulin, leading to energy storage; it also promotes the release of ghrelin from the stomach, and the large release of ghrelin generates hunger, triggering eating behavior. Studies in corresponding populations have shown that increasing prebiotic intake can increase the number of Bifidobacterium longum and pseudobifidobacterium in the gut, reduce the total amount of SCFAs and acetate in feces, and simultaneously reduce serum LPS levels and the level of inflammation in the body. The gut microbiota-brain-pancreatic β-cell axis enables foraging animals to ingest large amounts of calories in a short period. However, in today's world where high-calorie foods are prevalent, it promotes obesity and its related complications such as hyperlipidemia, fatty liver, and insulin resistance. When the human body ingests prebiotics, gut probiotics can produce butyrate, which participates in the release of intestinal hormones, thereby reducing fat accumulation and blood sugar elevation. Butyrate also has the effect of reducing inflammation and maintaining immune balance. Compared with leaner healthy individuals, obese and overweight individuals have been found to have more acetate and SCFAs in their feces, confirming the regulatory role of microbial metabolites in neuroendocrine function. In summary, using gut microbiota as a new target, the body's energy absorption and consumption balance can be affected through multiple pathways, including energy regulation, inflammation, and gut endocrine regulation. Therefore, further exploring the mechanisms by which gut microbiota affects obesity will become a new direction for future research on the pathogenesis of obesity, providing new "personalized" concepts and safer and more effective approaches for the prevention and treatment of obesity and other metabolic diseases. Section 2 Energy Metabolism in Obesity I. Human Energy Consumption Human energy consumption includes basal metabolism, physical activity, and the thermic effect of food, as well as other consumption in special populations, such as the growth and development needs of minors, the additional needs during pregnancy and lactation, and the rehabilitation needs of trauma patients. Based on individual differences, adult energy consumption can be measured or assessed. Basal metabolism accounts for approximately 65%–70% of total human energy consumption, physical activity accounts for approximately 15%–30%, and the thermic effect of food accounts for approximately 10%. The proportions of these three components are roughly fixed in normal individuals, but may vary in obese or disease states. 1. Basal Metabolism and Resting Energy Consumption Basal metabolism refers to the energy consumption of the human body under quiet and constant temperature conditions (1825℃), after fasting for 12 hours, while lying down, relaxed, and awake. Basal metabolism is the minimum energy consumption required to maintain bodily functions; the basal metabolism per unit time is called the basal metabolic rate (BMR). BMR testing is more complex. Resting energy expenditure (REE) is the energy expenditure under suitable temperature and quiet rest conditions, without fasting. Therefore, it is slightly higher than BMR, but the difference is small, generally less than 10%. Many factors influence basal metabolic rate (BMR), including: ① Height, weight, and body composition: a larger body surface area results in more heat loss through the body surface, thus increasing basal metabolic energy consumption. Lean body mass accounts for 70%–80% of basal metabolic rate, and there is a positive correlation between lean body mass and basal metabolic rate; ② Age and gender: women have less muscle mass and more fat mass, resulting in a lower basal metabolic rate than men. BMR increases during pregnancy and lactation, and the basal metabolic rate of the elderly is significantly lower than that of younger people; ③ Hormone levels: thyroxine can increase the metabolism of almost all cells, thereby increasing basal metabolic rate. Adrenaline can excite the sympathetic nervous system and increase heart rate, thus increasing basal metabolic rate; ④ Climate and temperature: basal metabolic rate decreases in suitable environments, while it increases in excessively high or low temperatures, with greater energy consumption in cold weather; ⑤ Others: caffeine, nicotine, and alcohol can increase bodily excitability, also raising basal metabolic rate. 2. Thermic Effect of Food (TEF): The thermic effect of food (TEF), also known as the specific dynamic action of food, refers to the extra energy expenditure resulting from eating. During the process of eating, the digestion, absorption, metabolism, and transformation of nutrients require additional energy, leading to an increase in body temperature and energy dissipation. Different foods have different TEFs: fats have the lowest TEF (4%–5%), carbohydrates 5%–6%, proteins 30%, and mixed foods 10%. 3. Physical Activity Expenditure: In addition to basal metabolism and the thermic effect of food, physical activity (PA) accounts for 15%–30% of total energy expenditure, with a higher percentage for those with higher activity levels. Whether it's exercise or daily work, physical activity consumes energy. Individual differences in physical activity expenditure are significant, depending on body size and exercise habits. Sedentary individuals experience significantly reduced physical activity expenditure; it is also clearly correlated with muscle mass, with larger muscle mass resulting in greater physical activity expenditure. When estimating energy requirements, physical activity can be categorized as mild, moderate, and severe, and assigned different energy coefficients.

Article 16