GPR120 promotes adipogenesis through intracellular calcium and extracellular signal-regulated kinase 1/2 signal pathway

Song, Tongxing; Zhou, Yuanfei; Peng, Jian; Tao, Ya‐Xiong; Yang, Yang; Xu, Tao; Ren, Jiao; Xiang, Quanhang; Wei, Hong

doi:10.1016/j.mce.2016.06.009

Cited by 47 publications

(24 citation statements)

References 42 publications

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“…Our present study was not consistent with this previous examination [32]. Song et al reported that GPR120 stimulation promote adipogenesis and triglyceride accumulation in cultured 3T3-L1 adipocytes [33]. These newly differentiated adipocytes might act as energy store and improve glucose tolerance [34].…”

Section: Discussioncontrasting

confidence: 97%

Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1 adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice

et al. 2017

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BackgroundSaturated fatty acids have been shown to cause insulin resistance and low-grade chronic inflammation, whereas unsaturated fatty acids suppress inflammation via G-protein coupled receptor 120 (GPR120) in macrophages. However, the anti-inflammatory effects of unsaturated fatty acids in adipocytes have yet to be elucidated. Hence, the aims of the present study were to evaluate the anti-inflammatory effects of eicosapentaenoic acid (EPA) via GPR120 in adipocytes.MethodsWe used 250 μM palmitate as a representative saturated fatty acid. 3T3-L1 adipocytes were used for in vitro studies. We further evaluated the effect of EPA supplementation in a high-fat/high-sucrose (HFHS) diet-induced adipose tissue inflammatory mouse model.ResultsEPA attenuated palmitate-induced increases in inflammatory gene expression and NF-κB phosphorylation in 3T3-L1 adipocytes. Silencing of GPR120 abolished the anti-inflammatory effects of EPA. In GPR120 downstream signal analysis, EPA was found to decrease palmitate-induced increases in TAK1/TAB1 complex expression. EPA supplementation suppressed HFHS-induced crown-like structure formation in epididymal adipose tissue and altered macrophage phenotypes from M1 to M2 in the stromal vascular fraction. Moreover, the EPA-containing diet attenuated increases in adipose p-JNK and phospho-p65 NF-κB levels.ConclusionsIn conclusion, the findings of the present study demonstrate that EPA suppresses palmitate-induced inflammation via GPR120 by inhibiting the TAK1/TAB1 interaction in adipocytes. EPA supplementation reduced HFHS diet-induced inflammatory changes in mouse adipose tissues. These results demonstrate adipose GPR120 as a potential therapeutic target for decreasing inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-017-0188-0) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 97%

Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1 adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice

et al. 2017

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“…Intracellular calcium level was measured as described previously (Song et al, 2016;Zhou et al, 2016). Briefly, the bPMEC were seeded into 96-well assay plates with black sides and a clear bottom and incubated for 24 h. Cells were starved overnight in serum-free medium before treatment with AA-free KRBH containing 0.1% BSA for 2 h. Four micromoles per liter of the Ca 2+ -sensitive indicator dye Fluo-8 a.m. (AAT Bioquest, Sunnyvale, CA) was added for 1 h; cells were then washed twice with Hanks' balanced salt solution (HBSS; without Ca 2+ ; catalog no.…”

Section: [Ca 2+ ]I Measurementmentioning

confidence: 99%

Methionine and valine activate the mammalian target of rapamycin complex 1 pathway through heterodimeric amino acid taste receptor (TAS1R1/TAS1R3) and intracellular Ca2+ in bovine mammary epithelial cells

Zhou

Peng

et al. 2018

Journal of Dairy Science

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Amino acids play a key role in regulating milk protein synthesis partly through activation of the mammalian target of rapamycin (mTOR) signaling pathway. However, the involvement of extracellular AA sensing receptors in this process is not well understood. In nonruminants, it is well established that the AA taste 1 receptor member 1/3 (TAS1R1/TAS1R3) heterodimer contributes to the sensing of most l-AA. Whether this receptor is functional in bovine mammary cells is unknown. The objective of this study was to determine essential AA signaling through TAS1R1/TAS1R3 and their roles in regulating mTOR signaling pathway and casein mRNA abundance in primary bovine mammary epithelial cells and the Mac-T cell line. The bovine mammary epithelial cells were stimulated with complete Dulbecco's modified Eagle's medium (+EAA), medium without EAA (−EAA), or medium supplemented with only 1 of the 10 essential AA, respectively. The nonessential AA levels were the same across all treatments. Small interference RNA targeting TAS1R1 were designed and transfected into bovine primary mammary epithelial cells (bPMEC). Supplementation of a complete mixture of essential AA or Arg, Val, Leu, His, Phe, Met, and Ile individually led to greater mTOR phosphorylation. Phosphorylation of ribosomal protein S6 kinase β-1 was greater in the presence of Val, Leu, Trp, Met, and Ile. Valine, Leu, Met, and Ile led to greater eIF4E-binding protein 1 phosphorylation. Although +EAA and a few individual AA tested induced increases in intracellular calcium, Met and Val were the most potent. Knockdown of TAS1R1 decreased intracellular calcium in bPMEC cultured with both Val and Met. Phosphorylation of mTOR, ribosomal protein S6 kinase β-1, and eIF4E-binding protein 1 was lower when TAS1R1 was knocked-down in bPMEC supplemented with Val and Met. In addition, small interference RNA silencing of TAS1R1 resulted in lower β-casein (CSN2) abundance. The TAS1R1/TAS1R3 receptor may sense extracellular AA and activate mTOR signaling in bovine mammary cells, likely by elevating intracellular calcium concentration. This mechanism appears to have a role in Met-and Val-induced changes in CSN2 mRNA abundance. Further in vivo studies will have to be performed to assess the relevance of this mechanism in the mammary gland.

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“…GPR120 knockout mice become obese on a high fat diet and exhibit multiple metabolic disorders, including insulin resistance associated with reduced insulin signalling and enhanced inflammation in white adipose tissue (Ichimura et al, 2012). Other functions attributed to GPR120 in adipose tissue include the promotion of adipogenesis (Song et al, 2016) and the stimulation of VEGF-A production by mature adipocytes (Hasan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

IL-1β and TNFα inhibit GPR120 (FFAR4) and stimulate GPR84 (EX33) and GPR41 (FFAR3) fatty acid receptor expression in human adipocytes: implications for the anti-inflammatory action of n-3 fatty acids

Muredda

Kępczyńska

Zaïbi

et al. 2017

Archives of Physiology and Biochemistry

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Regulation of the expression of GPCR fatty acid receptor genes has been examined in human adipocytes differentiated in culture. TNFα and IL-1β induced a marked reduction in GPR120 expression, mRNA level falling 17-fold at 24 h in adipocytes incubated with TNFα. In contrast, GPR84 mRNA was dramatically increased by these cytokines (>500-fold for IL-1β at 4 h); GPR41 expression was also stimulated. Rosiglitazone did not affect GPR84 expression, but GPR120 and GPR41 expression increased. Dexamethasone, insulin, linoleic and docosahexaenoic acids (DHA), and TUG891 (GPR120 agonist) had little effect on GPR120 and GPR84 expression. TUG891 did not attenuate the pro-inflammatory actions of TNFα and IL-1β. DHA slightly countered the actions of IL-1β on CCL2, IL6 and ADIPOQ expression, though not on secretion of these adipokines. GPR120 and GP84 gene expression in human adipocytes is highly sensitive to pro-inflammatory mediators; the inflammation-induced inhibition of GPR120 expression may compromise the anti-inflammatory action of GPR120 agonists.

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GPR120 promotes adipogenesis through intracellular calcium and extracellular signal-regulated kinase 1/2 signal pathway

Cited by 47 publications

References 42 publications

Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1 adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice

Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1 adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice

Methionine and valine activate the mammalian target of rapamycin complex 1 pathway through heterodimeric amino acid taste receptor (TAS1R1/TAS1R3) and intracellular Ca2+ in bovine mammary epithelial cells

IL-1β and TNFα inhibit GPR120 (FFAR4) and stimulate GPR84 (EX33) and GPR41 (FFAR3) fatty acid receptor expression in human adipocytes: implications for the anti-inflammatory action of n-3 fatty acids

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