- Peptide, (C)NVASFINPDLEGSWRK corresponding to amino acid residues 244-259 of rat FFAR1 (Accession Q8K3T4).
- Rat pancreas lysate (1:200).
- Western blot analysis of rat pancreas lysate:1. Anti-GPR40/FFAR1 (extracellular) Antibody (#AFR-011), (1:200).
2. Anti-GPR40/FFAR1 (extracellular) Antibody, preincubated with GPR40/FFAR1 (extracellular) Blocking Peptide (#BLP-FR011).
- Rat brain sections.
Free fatty acids (FFAs) were for long believed to influence cellular metabolism. Hoever, the discovery that FFAs actually mediate their effects through one of three G-protein coupled receptors (GPCRs) - Free Fatty Acid Receptors 1-3 (FFAR1-3), has initiated a number of studies in order to assess their implication in health and disease1.
Like all other GPCRs, FFAR1-3 have seven transmembrane domains, an extracellular N-terminal tail and an intracellular C-terminus.
FFAR1 is activated by either medium or long, saturated or unsaturated fatty acids2,3, whereas FFAR2 and FFAR3 are activated by short chain fatty acids4,5. FFAR1 is coupled to Gq and leads to Ca2+ mobilization upon activation. FFAR2 couples to both pertussis-sensitive and insensitive G-proteins and also leads to increased intracellular Ca2+ levels. FFAR3 coupling to G-protein induces an increase in cAMP1.
Distribution studies of all three FFA Receptors indicate that FFAR1 mRNA is quite elevated in the pancreas2,3. FFAR1 is also detected in the liver, heart, skeletal muscle, and brain; although this broad localization pattern is supported only by one study2. FFAR2 is expressed in many tissues like liver and colon6. FFAR3 is expressed in many tissues but shows highest expression in adipose tissue4. Relatively high expression of the receptor could be detected in pancreas, spleen, lymph nodes and bone marrow4,5.
As mentioned above, the finding that FFAs’ actions are mediated by GPCRs, prompted many studies in order to elucidate their roles in healthy and disease states. Such studies stipulate that FFAR1 may be involved in obesity and type 2 diabetes since circulating free fatty acid levels in the plasma are significantly elevated. On the other hand, FFAR2 and FFAR3 could be potential targets for treating irritable bowel disease and appetite control1.