GLP is known to be

GLP-1 is known to be expressed in a subset of taste bud cells and has been shown to co-localize with GPR120 in the circumvallate papillae [22]. Local GLP-1 regulates taste preference for sucrose [54]. Analogous to intestinal mediation of GLP-1 by GPR120, Martin et al.[22] report induction of GLP-1 secretion from circumvallate papillae following stimulation with α-LA and GSK137647A. Thus, by means of increasing oral GLP-1 secretion, GPR120 might also be able to modulate preference for dietary Blebbistatin mg as well as FAs. GPR120 could therefore be expected to act as a determinant of dietary composition and manipulation of this function could attenuate overconsumption of energy-dense foods. However it seems that GPR120 activation might promote preferential intake of foods high in FAs and sucrose, therefore modulation of spontaneous taste preference could present a unique role for GPR120 antagonism. Thus, further studies should investigate this effect in free feeding wild-type and GPR120−/− mice to ascertain the impact of spontaneous taste preference in relation to bodyweight.
Inflammation GPR120 is expressed abundantly in adipose tissues and in macrophages [8]. GPR120 has been shown to exert powerful anti-inflammatory effects [8], which is consistent with activation of GPR120 via omega 3 FAs, α-LA and DHA. These FAs have been widely validated as having anti-inflammatory effects at the tissue-specific and systemic levels [55]. In the study by Oh et al.[8], GPR120 was shown to mediate suppression of the proinflammatory markers IKKβ, JNK, TNF-α, interleukin-6 and toll-like receptor-4 in vitro and reduce macrophage infiltration of adipose tissues through decreased chemotaxis in wild-type but not GPR120−/− mice. Consistent with this, GPR120 is localized in macrophages with the expression of this receptor being induced by obesity, a pro-inflammatory state, in these cells [8]. In the same study Oh et al. [8] show that the expression of pro-inflammatory genes in M1 macrophages was decreased whilst the expression of M2 anti-inflammatory genes were increased in wild-type but not GPR120−/− mice fed a high fat diet supplemented with omega-3 FAs. Cintra et al. [20] further show that following acute injection of omega-3 or omega-9 FAs intracerebroventricularly, GPR120 couples with β-arrestin2 to dissociate TAK1 binding protein from TAK1 and thus reduce the activity of inflammatory pathways, including those mediated by toll-like receptor-4 and tumor necrosis factor (TNF)-α. Considered together, this provides compelling evidence that GPR120 is an anti-inflammatory receptor, with macrophage GPR120 possibly being a crucial mediator of these effects.
GPR120 and insulin signaling The skeletal muscle is a major site of insulin-stimulated glucose uptake 56, 57 and thus is implicit in maintaining systemic euglycaemia. Cornall et al.[15] show increased GPR120 mRNA expression in the EDL skeletal muscle which comprises predominantly glycolytic and/or fast-twitch fibers 58, 59, therefore relying largely on glucose for energy production. Activity at GPR120 has been shown to have insulin-sensitizing effects [8] and protects from glucose intolerance induced by ingestion of a high fat diet [5]. Consistent with this, GPR120 knockout in mice decreases phosphorylation of IRβ and IRS1 in white adipose tissues and IRS1 and IRS2 in the liver [5], all of which are important regulators of insulin-stimulated glucose uptake. This decreased phosphorylation was accompanied by increased fasting glucose and impaired responses to insulin and glucose tolerance testing in GPR120−/− mice fed a high fat diet [5]. Likewise, GPR120 was shown to promote glucose transporter 4 translocation in 3T3-L1 adipocytes and directly enhanced glucose uptake via Gαq signaling [8], which is additive to improved insulin sensitivity. However this effect was not observed in L6 muscle cells, which could be explained by the lack of expression reported in these cells in this particular study [8].