S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction.
S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction.
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DOI：
10.1080/21623945.2021.2021700
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发表时间：
2022-12
期刊：
影响因子：
3.3
通讯作者：
Samad F
中科院分区：
文献类型：
--
作者：
Chakrabarty S;Bui Q;Badeanlou L;Hester K;Chun J;Ruf W;Ciaraldi TP;Samad F
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that interacts via 5 G-protein coupled receptors, S1PR1-5, to regulate signalling pathways critical to biological processes including cell growth, immune cell trafficking, and inflammation.We demonstrate that in Type 2 diabetic (T2D) subjects, plasma S1P levels significantly increased in response to the anti-diabetic drug, rosiglitazone, and, S1P levels correlated positively with measures of improved glucose homeostasis. In HFD-induced obese C57BL/6 J mice S1PR3 gene expression was increased in adipose tissues (AT) and liver compared with low fat diet (LFD)-fed counterparts. On a HFD, weight gain was similar in both S1PR3-/- mice and WT littermates; however, HFD-fed S1PR3-/- mice exhibited a phenotype of partial lipodystrophy, exacerbated insulin resistance and glucose intolerance. This worsened metabolic phenotype of HFD-fed S1PR3-/- mice was mechanistically linked with increased adipose inflammation, adipose macrophage and T-cell accumulation, hepatic inflammation and hepatic steatosis. In 3T3-L1 preadipocytes S1P increased adipogenesis and S1P-S1PR3 signalling regulated the expression of PPARγ, suggesting a novel role for this signalling pathway in the adipogenic program. These results reveal an anti-diabetic role for S1P, and, that S1P-S1PR3 signalling in the adipose and liver defends against excessive inflammation and steatosis to maintain metabolic homeostasis at key regulatory pathways.
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影响因子：
8.1
作者：
Holland WL;Xia JY;Johnson JA;Sun K;Pearson MJ;Sharma AX;Quittner-Strom E;Tippetts TS;Gordillo R;Scherer PE
通讯作者：
Scherer PE
影响因子：
16.6
作者：
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通讯作者：
Bhatnagar, Seema
影响因子：
3.6
作者：
Imeri, Faik;Blanchard, Olivier;Huwiler, Andrea
通讯作者：
Huwiler, Andrea
DOI：
10.1073/pnas.1221309110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Awojoodu, Anthony O.;Ogle, Molly E.;Botchwey, Edward
通讯作者：
Botchwey, Edward
DOI：
10.1073/pnas.1802611115
发表时间：
2018-05-29
影响因子：
11.1
作者：
Hill, David A.;Lim, Hee-Woong;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.