Potential roles of GPR120 and its agonists in the management of diabetes

Zhang, Dan; Leung, Po Sing

doi:10.2147/dddt.s53892

Cited by 29 publications

(20 citation statements)

References 111 publications

(281 reference statements)

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“…This receptor was slightly upregulated only after exposure to SIPERNAT ® 350, which is a precipitated form of SAS with the lowest specific surface area of all investigated precipitated SAS materials. GPR120 is known to influence glucose uptake and inflammation (Oh et al 2010;Song et al 2017;Zhang and Leung, 2014). However, we did not detect any significant changes in the release of the pro-inflammatory cytokines IL-8 and CCL2 after treatment with SIPERNAT ® 350 or any other SAS material.…”

Section: Discussioncontrasting

confidence: 71%

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model

et al. 2020

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E 551, also known as synthetic amorphous silica (SAS), is the second most produced food additive. However, according to the re-evaluation of E 551 by the European Food Safety Authority (EFSA) in 2018, the amount of available data on the oral toxicity of food grade E 551 is still insufficient for reliable risk assessment. To close this gap, this study aimed to investigate six food-grade SAS with distinct physicochemical properties on their interaction with the intestinal barrier using advanced in vitro intestinal co-cultures and to identify potential structure–activity relationships. A mucus-secreting Caco-2/HT-29/Raji co-culture model was treated with up to 50 µg/ml SAS for 48 h, which represents a dose range relevant to dietary exposure. No effects on cell viability, barrier integrity, microvilli function or the release of inflammatory cytokine were detected after acute exposure. Slight biological responses were observed for few SAS materials on iron uptake and gene expression levels of mucin 1 and G-protein coupled receptor 120 (GPR120). There was no clear correlation between SAS properties (single or combined) and the observed biological responses. Overall, this study provides novel insights into the short-term impact of food-relevant SAS with distinct characteristics on the intestinal epithelium including a range of intestine-specific functional endpoints. In addition, it highlights the importance of using advanced intestinal co-cultures embracing relevant cell types as well as a protective mucus barrier to achieve a comprehensive understanding of the biological response of food additives at the intestinal barrier in vitro.

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Section: Discussioncontrasting

confidence: 71%

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model

et al. 2020

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“…Interestingly, GPR120 is expressed primarily on Kupffer cells in the liver with minimal expression in hepatocytes [35], while hepatic lipid metabolism takes place in hepatocytes. While this study does not address this specifically, one plausible hypothesis is that FOLEmediated GPR120 signaling in hepatic Kupffer cells results in release of factors that act in a paracrine fashion on hepatocytes to attenuate PPARγ-mediated CD36 and SCD1 activity.…”

Section: Discussionmentioning

confidence: 99%

Fish oil protects the liver from parenteral nutrition-induced injury via GPR120-mediated PPARγ signaling

Fell

Cho

Dao

et al. 2019

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Intravenous fish oil lipid emulsions (FOLE) can prevent parenteral nutrition (PN)-induced liver injury in murine models and reverse PN-induced cholestasis in pediatric patients. However, the mechanisms by which fish oil protects the liver are incompletely characterized. Fish oil is rich in omega-3 fatty acids, which are ligands for the G-protein coupled receptor 120 (GPR120), expressed on hepatic Kupffer cells. This study tested the hypothesis that FOLE protects the liver from PN-induced injury through GPR120 signaling. Utilizing a previously described murine model of PN-induced liver injury in which mice develop steatosis in response to an oral parenteral nutrition diet, FOLE was able to preserve normal hepatic architecture in wild type mice, but not in congenic GPR120 knockout (gpr120 −/−) mice. To further characterize the requirement of intact GPR120 for FOLE-mediated hepatic protection, gene expression profiles of key regulators of fat metabolism were measured. PPARγ was identified as a gene that is up-regulated by the PN diet and normalized with the addition of FOLE in wild type, but not in gpr120 −/− mice. This was confirmed at the protein expression level. A PPARγ expression array further identified CD36 and SCD1, both downstream effectors of PPARγ, to be up-regulated in PN-fed wild type mice yet normalized upon FOLE administration in wild type but not in gpr120 −/− mice. Together, these results suggest that FOLE protects the liver, in part, through activation of GPR120 and the downstream effectors PPARγ and CD36. Identification of key genetic determinants of FOLE

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“…GPR120 is widely expressed in various tissue and cell types, including intestinal tissue, adipose tissue, macrophages, and pancreas [13,14]. GPR120 could also participate in metabolic disorders through regulating the secretion of gut hormone and insulin, food preference, and glucose homeostasis [15]. Interestingly, GPR120 has displayed a robust anti-inflammatory property in macrophages and adipocytes by inhibiting NF-κB activation [16].…”

Section: Introductionmentioning

confidence: 99%

Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

Zhang

et al. 2020

Aging

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Osteoarthritis (OA) is a whole-joint disease with extremely high prevalence. In all treatment approaches of OA, blocking the degradation of the cartilage extracellular matrix is an important treatment. In OA, overexpression of derivative enzymes leads to excessive catabolism and reduced synthesis of cartilage including type II collagen and aggrecan, which results in irreversible destruction of the joint. SOX9 is a transcription factor that regulates the synthesis of type II collagen and aggrecan and is significantly downregulated in OA. GPR120 has been reported to affect the pathophysiology of OA. In this study, we used the GPR120 agonist GW9508 and TUG891 in ATDC5 chondrocytes exposed to interleukin (IL)-1β to investigate the involvement of GPR120 in SOX9mediated expression of type II collagen and aggrecan. Our findings show that agonism of GPR120 can reduce inflammation by inhibiting the expression of IL-6 and IL-8 induced by IL-1β. We also show that GW9508 and TUG891 rescue the expression of type II collagen and aggrecan by preventing the reduction of SOX9 expression. Additionally, we demonstrate that the effects of GW9508 on SOX9 expression are mediated through CREB and that GPR120 is indeed required for this effect. Thus, agonism of GPR120 by GW9508 might be a potential therapeutic strategy to halt or prevent cartilage degradation.

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Potential roles of GPR120 and its agonists in the management of diabetes

Cited by 29 publications

References 111 publications

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model

Fish oil protects the liver from parenteral nutrition-induced injury via GPR120-mediated PPARγ signaling

Agonism of GPR120 prevented IL-1β-induced reduction of extracellular matrix through SOX-9

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