Abstract
Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. In addition, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein-coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid-activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids like acetate, propionate, and butyrate, whereas FFAR1 and FFAR4 are activated by medium- and long-chain fatty acids like palmitate, oleate, linoleate, and others. FFARs have attracted considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here, we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR-based therapies to treat patients with obesity and Type 2 diabetes.
Highlights
Free fatty acids (FFAs) play a vital role as energy substrates and form key components of cellular membranes
Several independent studies have documented the expression of FFAR2 and FFAR4 in human and mouse adipose tissue and cultured adipocytes [8,18,19]
Numerous studies have demonstrated that FFAR2 is expressed in human and mouse white adipose tissue (WAT), and in the murine adipocyte cell line 3T3L1 [33–35]
Summary
Free fatty acids (FFAs) play a vital role as energy substrates and form key components of cellular membranes. FFAs have been shown to activate cell surface receptors known as Free Fatty Acid Receptors (FFARs). Free fatty acids have been shown to activate signaling cascades involving GPCRs. To date, four FFARs have been identified that act as ligands for FFAs based on their chain length (Figure 1). FFAR-mediated signaling has been implicated in metabolic processes like insulin secretion from pancreatic beta cells, incretin secretion from entero-endocrine cells, regulation of food intake, adipose tissue biology, and many more [6,7,10–13]. These receptors are considered attractive therapeutic targets for metabolic disorders like obesity and type 2 diabetes. We focus on the role of FFARs in regulating various aspects of adipose biology, including adipogenesis, lipid, and glucose metabolism, and explore the prospect of FFAR-based therapies to treat patients with metabolic disorders
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