This review examines the multifaceted role of adiponectin, a predominant adipokine released by adipose tissue (AT), in glucose and fatty acid metabolism. AT, composed mainly of adipocytes, plays a critical role in lipid control, metabolism, and energy storage. It is now recognized as a dynamic endocrine organ that regulates food intake, energy homeostasis, insulin sensitivity, thermoregulation, and immune responses. Adiponectin, a protein hormone, is crucial for maintaining systemic metabolic homeostasis. Its levels are negatively associated with insulin resistance, a key characteristic of metabolic diseases such as type 2 diabetes, cardiovascular disease, and fatty liver disease. The review explores the regulatory mechanisms of adiponectin, its physiological effects, and its potential as a therapeutic target. It also analyzes the impact of dietary patterns, specific nutrients, and physical activities on adiponectin levels, highlighting strategies to improve metabolic health. Key points include: 1. **Adipose Tissue (AT)**: AT is a metabolically active endocrine organ that regulates food intake, energy homeostasis, insulin sensitivity, thermoregulation, and immune responses. It is composed of adipocytes, which store triglycerides and secrete various hormones and proteins. 2. **Adiponectin**: - **Structure and Receptors**: Adiponectin is encoded by the ADIPQ gene and exists in various oligomeric forms. It acts through receptors AdipoR1 and AdipoR2, mediating its effects on energy expenditure, insulin sensitivity, and anti-inflammatory responses. - **Physiological Functions**: Adiponectin enhances insulin sensitivity, promotes fatty acid oxidation, and exerts anti-inflammatory effects. It is involved in maintaining metabolic homeostasis across various organs, including the liver, kidneys, skeletal muscle, cardiovascular system, central nervous system, and bones. 3. **Role in Diseases**: - **Cardiovascular Disease**: Low levels of adiponectin are associated with an increased risk of cardiovascular diseases. Increasing adiponectin levels can improve cardiovascular outcomes. - **Type 2 Diabetes and Obesity**: Adiponectin improves insulin sensitivity and reduces inflammation. Lower plasma adiponectin levels are linked to insulin resistance and type 2 diabetes. - **Nonalcoholic Fatty Liver Disease (NAFLD)**: Lower adiponectin levels are associated with NAFLD, impairing its ability to activate pathways crucial for reducing hepatic glucose production and enhancing fatty acid oxidation. - **Alzheimer's Disease**: Adiponectin's ability to improve insulin sensitivity may play a protective role against Alzheimer's disease. - **Cancer**: Lower adiponectin levels are associated with an increased risk of certain cancers, such as breast and colorectal cancer. 4. **Influence of Diet on Adiponectin**: - **EnergyThis review examines the multifaceted role of adiponectin, a predominant adipokine released by adipose tissue (AT), in glucose and fatty acid metabolism. AT, composed mainly of adipocytes, plays a critical role in lipid control, metabolism, and energy storage. It is now recognized as a dynamic endocrine organ that regulates food intake, energy homeostasis, insulin sensitivity, thermoregulation, and immune responses. Adiponectin, a protein hormone, is crucial for maintaining systemic metabolic homeostasis. Its levels are negatively associated with insulin resistance, a key characteristic of metabolic diseases such as type 2 diabetes, cardiovascular disease, and fatty liver disease. The review explores the regulatory mechanisms of adiponectin, its physiological effects, and its potential as a therapeutic target. It also analyzes the impact of dietary patterns, specific nutrients, and physical activities on adiponectin levels, highlighting strategies to improve metabolic health. Key points include: 1. **Adipose Tissue (AT)**: AT is a metabolically active endocrine organ that regulates food intake, energy homeostasis, insulin sensitivity, thermoregulation, and immune responses. It is composed of adipocytes, which store triglycerides and secrete various hormones and proteins. 2. **Adiponectin**: - **Structure and Receptors**: Adiponectin is encoded by the ADIPQ gene and exists in various oligomeric forms. It acts through receptors AdipoR1 and AdipoR2, mediating its effects on energy expenditure, insulin sensitivity, and anti-inflammatory responses. - **Physiological Functions**: Adiponectin enhances insulin sensitivity, promotes fatty acid oxidation, and exerts anti-inflammatory effects. It is involved in maintaining metabolic homeostasis across various organs, including the liver, kidneys, skeletal muscle, cardiovascular system, central nervous system, and bones. 3. **Role in Diseases**: - **Cardiovascular Disease**: Low levels of adiponectin are associated with an increased risk of cardiovascular diseases. Increasing adiponectin levels can improve cardiovascular outcomes. - **Type 2 Diabetes and Obesity**: Adiponectin improves insulin sensitivity and reduces inflammation. Lower plasma adiponectin levels are linked to insulin resistance and type 2 diabetes. - **Nonalcoholic Fatty Liver Disease (NAFLD)**: Lower adiponectin levels are associated with NAFLD, impairing its ability to activate pathways crucial for reducing hepatic glucose production and enhancing fatty acid oxidation. - **Alzheimer's Disease**: Adiponectin's ability to improve insulin sensitivity may play a protective role against Alzheimer's disease. - **Cancer**: Lower adiponectin levels are associated with an increased risk of certain cancers, such as breast and colorectal cancer. 4. **Influence of Diet on Adiponectin**: - **Energy