Abstract
Free fatty acid receptors (FFARs) are a class of G protein-coupled receptors (GPCRs) that have wide-ranging effects on human physiology. The four well-characterized FFARs are FFAR1/GPR40, FFAR2/GPR43, FFAR3/GPR41, and FFAR4/GPR120. Short-chain (<6 carbon) fatty acids target FFAR2/GPR43 and FFAR3/GPR41. Medium- and long-chain fatty acids (6–12 and 13–21 carbon, respectively) target both FFAR1/GPR40 and FFAR4/GPR120. Signaling through FFARs has been implicated in non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), intestinal failure-associated liver disease (IFALD), and a variety of other liver disorders. FFARs are now regarded as targets for therapeutic intervention for liver disease, diabetes, obesity, hyperlipidemia, and metabolic syndrome. In this review, we provide an in-depth, focused summary of the role FFARs play in liver health and disease.
Highlights
According to the WHO, in 2016 nearly 40% of adults worldwide were overweight and, of those, 13% were obese
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are obesity-related conditions that continue to increase in prevalence as the global obesity epidemic worsens (Mantovani et al, 2020)
Experimental models of these liver diseases used in conjunction with FFAR1 knockout animals and/or FFAR1 antagonists offer the potential to further elucidate the disease mechanisms and better characterize FFAR1 as a target for therapeutic intervention with omega-3 fatty acid (FA) or FFAR1specific agonists
Summary
According to the WHO, in 2016 nearly 40% of adults worldwide were overweight and, of those, 13% were obese. Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are obesity-related conditions that continue to increase in prevalence as the global obesity epidemic worsens (Mantovani et al, 2020). T2DM, and NAFLD are an intimately related set of conditions that each contribute to the metabolic syndrome phenotype (Lusis et al, 2008). The effects of FFAR signaling on these conditions and the potential for therapeutic intervention through these receptors have only recently been investigated. While some degree of overlap exists, each FFAR is characterized by a unique combination of tissue-specific expression, FA agonist affinity, and signaling and metabolic effects (Figure 1). The physiologic interplay between obesity, T2DM, and NAFLD centers FFARs as prime therapeutic targets for these conditions. Intestinal failureassociated liver disease (IFALD) and other metabolic liver disorders may benefit from
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
