FFAR - Free Fatty Acid Receptor | Elisa - Clia - Antibody - Protein

Background:

Free Fatty Acid Receptors (FFARs), also known as G protein-coupled receptors (GPCRs) for fatty acids, are a group of receptors that play essential roles in sensing and responding to fatty acids in various tissues throughout the body. FFARs were discovered relatively recently, with the first receptor, FFAR1 (formerly known as GPR40), identified in the early 2000s through bioinformatics and functional studies. FFARs are evolutionarily conserved across species, highlighting their importance in metabolic regulation and energy homeostasis. FFARs are activated by free fatty acids, particularly medium- to long-chain fatty acids such as palmitic acid, oleic acid, and linoleic acid. FFAR2 and FFAR3 are specifically activated by short-chain fatty acids produced by the fermentation of dietary fiber in the gut.FFARs are expressed in various tissues, including adipose tissue, pancreatic β-cells, enteroendocrine cells of the gastrointestinal tract, liver, skeletal muscle, and immune cells.

Structural Features:

• Transmembrane Protein: FFARs are seven-transmembrane domain receptors, characteristic of GPCRs.
• Topology: They consist of an extracellular N-terminus, seven transmembrane helices connected by intracellular and extracellular loops, and an intracellular C-terminus.
• Binding Site: The ligand-binding pocket for fatty acids is located within the transmembrane domain.

Subtypes and Classification:

• There are several subtypes of FFARs, including FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41), FFAR4 (GPR120), and potentially others.
• FFARs are classified based on their primary sequence homology, ligand specificity, and downstream signaling pathways.  

Physiological Functions:

• Metabolic Regulation: FFARs play critical roles in regulating glucose and lipid metabolism, insulin secretion, and energy homeostasis.
• Incretin Hormone Secretion: FFAR1 and FFAR4 activation in pancreatic β-cells and enteroendocrine cells stimulates the release of incretin hormones such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).
• Immune Modulation: FFAR2 and FFAR3 activation on immune cells regulates immune responses, inflammation, and host-microbiota interactions.
• Gastrointestinal Function: FFARs influence gastrointestinal motility, nutrient absorption, and gut hormone secretion.

Clinical Implications:

• Type 2 Diabetes: Dysregulation of FFAR1 and FFAR4 signaling has been implicated in the pathogenesis of type 2 diabetes, making them potential therapeutic targets for improving insulin secretion and glucose homeostasis.
• Obesity: Altered FFAR1 and FFAR4 activity may contribute to obesity and metabolic syndrome, highlighting their role in energy balance and adipose tissue function.
• Inflammatory Disorders: FFAR2 and FFAR3 have been linked to the modulation of inflammatory responses and the pathogenesis of inflammatory bowel disease, asthma, and allergic disorders.
• Cardiovascular Disease: FFAR1 and FFAR4 activation may have protective effects on cardiovascular health through the regulation of lipid metabolism, inflammation, and vascular function.