The liver is a critical organ for metabolic regulation, with its activity controlled by insulin and other metabolic hormones. In the fed state, glucose is metabolized through glycolysis to produce pyruvate, which is then oxidized in the mitochondria to generate ATP. Excess glucose is used to synthesize fatty acids and store them as triacylglycerol (TAG) or cholesterol esters in lipid droplets. In the fasted state, the liver breaks down glycogen to release glucose and synthesizes new glucose through gluconeogenesis. Fasting also promotes lipolysis in adipose tissue, releasing nonesterified fatty acids (NEFAs) that are converted into ketone bodies in the liver, which serve as energy sources for extrahepatic tissues. Liver metabolism is regulated by neuronal and hormonal systems, with the sympathetic system stimulating and the parasympathetic system suppressing gluconeogenesis. Insulin promotes glycolysis and lipogenesis but inhibits gluconeogenesis, while glucagon counteracts insulin. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of enzymes involved in liver metabolism, thus regulating energy metabolism. Abnormal liver metabolism can lead to insulin resistance, diabetes, and nonalcoholic fatty liver disease (NAFLD). Glycogen metabolism involves glycogen synthesis in the fed state and glycogenolysis in the fasted state. Insulin stimulates glycogen synthesis by activating Akt, which inhibits GSK-3, while glucagon and catecholamines activate glycogen phosphorylase. Gluconeogenesis is regulated by the availability of substrates such as lactate, pyruvate, glycerol, and amino acids, as well as by transcription factors and coactivators like CREB, FOXO1, and C/EBPα. Gluconeogenesis is also influenced by metabolic states and the circadian clock, with SIRT and AMPK acting as energy sensors. Insulin suppresses gluconeogenesis by inhibiting FOXO1 and PGC-1α, while glucagon stimulates it by activating CREB and CRTC2. Growth hormone (GH) and nuclear receptors like GR and LXR also regulate gluconeogenesis. Cytokines and GI hormones, such as GLP-1 and FGF15/19, influence hepatic gluconeogenesis. Lipid metabolism in the liver involves fatty acid uptake, synthesis, and oxidation, with key enzymes like ACC, FAS, and SCD1 playing critical roles. Lipogenesis is controlled by transcription factors such as ChREBP, SREBP, and LXR, which regulate the expression of genes involved in fatty acid synthesis and storage. Abnormal lipid metabolism can lead to hepatic steatosis and other metabolic disorders.The liver is a critical organ for metabolic regulation, with its activity controlled by insulin and other metabolic hormones. In the fed state, glucose is metabolized through glycolysis to produce pyruvate, which is then oxidized in the mitochondria to generate ATP. Excess glucose is used to synthesize fatty acids and store them as triacylglycerol (TAG) or cholesterol esters in lipid droplets. In the fasted state, the liver breaks down glycogen to release glucose and synthesizes new glucose through gluconeogenesis. Fasting also promotes lipolysis in adipose tissue, releasing nonesterified fatty acids (NEFAs) that are converted into ketone bodies in the liver, which serve as energy sources for extrahepatic tissues. Liver metabolism is regulated by neuronal and hormonal systems, with the sympathetic system stimulating and the parasympathetic system suppressing gluconeogenesis. Insulin promotes glycolysis and lipogenesis but inhibits gluconeogenesis, while glucagon counteracts insulin. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of enzymes involved in liver metabolism, thus regulating energy metabolism. Abnormal liver metabolism can lead to insulin resistance, diabetes, and nonalcoholic fatty liver disease (NAFLD). Glycogen metabolism involves glycogen synthesis in the fed state and glycogenolysis in the fasted state. Insulin stimulates glycogen synthesis by activating Akt, which inhibits GSK-3, while glucagon and catecholamines activate glycogen phosphorylase. Gluconeogenesis is regulated by the availability of substrates such as lactate, pyruvate, glycerol, and amino acids, as well as by transcription factors and coactivators like CREB, FOXO1, and C/EBPα. Gluconeogenesis is also influenced by metabolic states and the circadian clock, with SIRT and AMPK acting as energy sensors. Insulin suppresses gluconeogenesis by inhibiting FOXO1 and PGC-1α, while glucagon stimulates it by activating CREB and CRTC2. Growth hormone (GH) and nuclear receptors like GR and LXR also regulate gluconeogenesis. Cytokines and GI hormones, such as GLP-1 and FGF15/19, influence hepatic gluconeogenesis. Lipid metabolism in the liver involves fatty acid uptake, synthesis, and oxidation, with key enzymes like ACC, FAS, and SCD1 playing critical roles. Lipogenesis is controlled by transcription factors such as ChREBP, SREBP, and LXR, which regulate the expression of genes involved in fatty acid synthesis and storage. Abnormal lipid metabolism can lead to hepatic steatosis and other metabolic disorders.