ADIPOR - Adiponectin receptor | Elisa - Clia - Antibody - Protein

Background

The adiponectin receptor (ADIPOR) is a cell surface receptor that mediates the biological effects of adiponectin, a protein hormone secreted by adipose tissue. There are two known types of adiponectin receptors, named adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). These receptors are encoded by the ADIPOR1 and ADIPOR2 genes, respectively. Adiponectin receptors belong to the class of seven-transmembrane domain receptors, also known as G protein-coupled receptors (GPCRs). They have an extracellular N-terminus, seven transmembrane helices, and an intracellular C-terminus. ADIPOR1 and ADIPOR2 exhibit distinct tissue distribution and signal transduction mechanisms. Adiponectin receptors specifically bind to adiponectin, allowing the hormone to exert its effects on target cells. Adiponectin exists in different oligomeric forms, including trimeric, hexameric, and high-molecular-weight complexes, and can interact with both ADIPOR1 and ADIPOR2. Activation of adiponectin receptors triggers intracellular signaling pathways that regulate various physiological processes, including glucose metabolism, fatty acid oxidation, insulin sensitivity, and anti-inflammatory responses. Adiponectin receptors play important roles in metabolic homeostasis and have implications for conditions such as obesity, insulin resistance, type 2 diabetes, and cardiovascular disease.ADIPOR1 and ADIPOR2 are expressed in various tissues, including adipose tissue, skeletal muscle, liver, and the cardiovascular system. Their expression patterns vary among tissues, suggesting tissue-specific roles for adiponectin signaling.

Protein Structure

Adiponectin receptors belong to a novel family of proteins with distinct structural characteristics:

• Transmembrane Domains: Both receptors have seven transmembrane domains, but unlike G-protein-coupled receptors (GPCRs), they have an internal N-terminus and an external C-terminus.
• Ligand Binding Domain: The extracellular domain binds to adiponectin, facilitating signal transduction across the membrane.
• C-terminal Tail: Involved in intracellular signaling and receptor regulation.

Classification and Subtypes

There are two main types of adiponectin receptors:

• AdipoR1: Predominantly expressed in skeletal muscle, it has a high affinity for the globular domain of adiponectin.
• AdipoR2: Predominantly expressed in the liver, it has an intermediate affinity for both the full-length and globular forms of adiponectin.

Function and Biological Significance

Adiponectin receptors play a vital role in mediating the physiological effects of adiponectin:

1. Insulin Sensitivity: Activation of AdipoR1 and AdipoR2 enhances insulin sensitivity by promoting glucose uptake and utilization in tissues.
2. Lipid Metabolism: Both receptors facilitate fatty acid oxidation and decrease lipid accumulation, contributing to overall lipid homeostasis.
3. Anti-inflammatory Effects: Adiponectin receptors inhibit pro-inflammatory signaling pathways, reducing the production of inflammatory cytokines.
4. Cardiovascular Protection: Through the activation of signaling pathways, these receptors contribute to endothelial function and reduce the risk of atherosclerosis.

Interactions

Adiponectin receptors interact with several key signaling molecules and pathways:

1. AMP-activated Protein Kinase (AMPK): Activation by adiponectin receptors enhances glucose uptake and fatty acid oxidation.
2. Peroxisome Proliferator-Activated Receptor Alpha (PPAR-α): Stimulation leads to increased fatty acid combustion and energy expenditure.
3. Mitogen-Activated Protein Kinase (MAPK): AdipoR1 and AdipoR2 modulate MAPK pathways involved in cellular growth and differentiation.
4. NF-κB Pathway: Inhibition of this pathway by adiponectin receptors reduces inflammation and cytokine production.

Clinical Significance

1. Metabolic Disorders: Variations in the ADIPOR1 and ADIPOR2 genes are associated with insulin resistance, type 2 diabetes, and metabolic syndrome. Understanding these variations can help in developing targeted therapies.
2. Cardiovascular Diseases: The protective effects of adiponectin receptors against atherosclerosis and other cardiovascular conditions make them potential therapeutic targets.
3. Non-alcoholic Fatty Liver Disease (NAFLD): Adiponectin receptor activity in the liver helps mitigate NAFLD by enhancing lipid metabolism and reducing liver inflammation.
4. Obesity: Reduced expression or function of adiponectin receptors is often observed in obesity, contributing to metabolic complications.

Summary

Adiponectin receptors, encoded by the ADIPOR1 and ADIPOR2 genes, are crucial for mediating the beneficial effects of adiponectin on glucose and lipid metabolism, inflammation, and cardiovascular health. AdipoR1, primarily found in skeletal muscle, and AdipoR2, mainly in the liver, activate key signaling pathways such as AMPK and PPAR-α, promoting metabolic homeostasis. These receptors also play roles in reducing inflammation and protecting against cardiovascular diseases. Clinically, alterations in adiponectin receptor function are linked to metabolic disorders, cardiovascular diseases, and obesity, highlighting their significance as therapeutic targets.