Dietary Fatty Acids and Their Potential for Controlling Metabolic Diseases Through Activation of FFA4/GPR120

Abstract

It is well known that the amount and type of ingested fat impacts the development of obesity and metabolic diseases, but the potential for beneficial effects from fat has received less attention. It is becoming clear that the composition of the individual fatty acids in diet is important. Besides acting as precursors of potent signaling molecules, dietary fatty acids act directly on intracellular and cell surface receptors. The free fatty acid receptor 4 (FFA4, previously GPR120) is linked to the regulation of body weight, inflammation, and insulin resistance and represents a potential target for the treatment of metabolic disorders, including type 2 diabetes and obesity. In this review, we discuss the various types of dietary fatty acids, the link between FFA4 and metabolic diseases, the potential effects of the individual fatty acids on health, and the ability of fatty acids to activate FFA4. We also discuss the possibility of dietary schemes that implement activation of FFA4.

IL-33 stimulates expression of the GPR84 (EX33) fatty acid receptor gene and of cytokine and chemokine genes in human adipocytes

“…The insulin sensitising and anti-inflammatory actions of GPR120, which is a receptor for n-3 polyunsaturated fatty acids [2][3], is unlikely to be modified by IL-33 contrary to what has been projected with IL-1β and TNFα [7]. The intracellular signalling pathways linked to the IL-33 receptor, ST2 (and its co-receptor IL-1 receptor accessory protein) [15], which are expressed in human adipocytes [11], would appear to be implicated in the modulation of the transcription of the GPR84 gene, but not GPR120.…”

“…Several G-protein coupled receptors act as sensors/receptors for fatty acids [1][2]. GPR120 (or FFAR4), is a receptor for n-3 polyunsaturated fatty acids, and has been linked to the antiinflammatory action of these lipids [2][3].…”

“…GPR120 (or FFAR4), is a receptor for n-3 polyunsaturated fatty acids, and has been linked to the antiinflammatory action of these lipids [2][3]. The primary ligands for GPR41 (FFAR3) and GPR43 (FFAR2) are short chain fatty acids, while GPR40 (FFAR1) is activated by medium and long chain saturated and mono-unsaturated fatty acids [1][2]. GPR84 (EX33), a pro-inflammatory receptor, is also activated by medium chain fatty acids [4][5].…”

“…GPR84 (EX33), a pro-inflammatory receptor, is also activated by medium chain fatty acids [4][5]. Each of these GPCRs has a distinct tissue distribution, with GPR120 being strongly expressed in both adipocytes and macrophages (M1 and M2) in white adipose tissue, where it promotes adipogenesis [6] in addition to insulin sensitising and anti-inflammatory actions [2][3]. Adipocytes also express GPR84, and at least in the case of human fat cells GPR40, GPR41 and GPR43, albeit at low levels [7].…”

Ginsenoside Rb2 enhances the anti-inflammatory effect of ω-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression

“…Macrophages directly participate in the process of obesity-induced chronic low-grade inflammation, which is tightly associated with macrophage infiltration into peripheral tissues and the pathogenesis of insulin resistance [32,33] . Recent research has indicated that GPR120 plays an important role in energy homeostasis, chronic inflammation and insulin resistance and represents a promising target for obesity and type 2 diabetes (T2DM) therapy [34] . In the present study, LPS-induced production of NO, TNF-α and IL-6 as well as expression of iNOS and COX-2 tended to be reduced by ALA. Incubation with Rb2 prior to ALA treatment dramatically amplified the inhibitory effect of ALA, leading to statistically significantly lower levels of these cytokines and pro-inflammatory enzymes than with ALA treatment alone.…”