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Gpr97 is dispensable for metabolic syndrome but is involved in macrophage inflammation in high-fat diet-induced obesity in mice.

Shi J, Zhang X, Wang S, Wang J, Du B, Wang Z, Liu M, Jiang W, Qian M, Ren H - Sci Rep (2016)

Bottom Line: Gpr97 is highly expressed in some immunocytes, but its potential role in inflammatory regulation has not been revealed clearly.Furthermore, the levels of TNF-α were higher in the liver and kidney of Gpr97(-/-) HFD mice compared to those in wild-type HFD mice.The data indicate that Gpr97 might be required for local inflammation development in obesity-relative tissues, but does not play a role in metabolic disorder in HFD-induced obesity.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

ABSTRACT
Local inflammation in tissues is one of primary causes in development of metabolic disorder in obesity. The accumulation of macrophages in some tissues can induce inflammatory reactions in obesity. Gpr97 is highly expressed in some immunocytes, but its potential role in inflammatory regulation has not been revealed clearly. In our research, we investigated Gpr97 in regulating macrophage inflammation and metabolic dysfunction in the high-fat diet (HFD)-induced obese mice. The major metabolic phenotyping were not different after Gpr97 knockout in HFD-fed mice. Similar pathological alterations in adipose tissue, liver, and kidney were observed in Gpr97(-/-) HFD mice compared with WT-HFD mice. In white adipose tissue, loss of Gpr97 reduced the ratio of M1-macrophages and increased the M2-macrophage ratio, which was opposite to that seen in the wild-type HFD mice. More macrophages invaded in the liver and kidney after Gpr97 knockout in HFD mice. Furthermore, the levels of TNF-α were higher in the liver and kidney of Gpr97(-/-) HFD mice compared to those in wild-type HFD mice. The data indicate that Gpr97 might be required for local inflammation development in obesity-relative tissues, but does not play a role in metabolic disorder in HFD-induced obesity.

No MeSH data available.


Related in: MedlinePlus

The HFD-induced inflammation analysis in kidney in the WT and Gpr97−/− mice.(a) The morphological evaluation of kidney by PAS staining after HFD fed in mice. (b) Detecting of macrophage makers F4/80 in mRNA level to determine invasion of macrophage into kidney in HFD mice. (c–e) The expression of relative markers in mRNA levels associated with M1-polarized macrophages in kidney of HFD-fed mice. (f–j) The analysis of markers of M2-polarized macrophages in mRNA level in kidney of HFD-fed mice. Data are shown as means ± s.e.m. (n = 8). *P < 0.05.
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f6: The HFD-induced inflammation analysis in kidney in the WT and Gpr97−/− mice.(a) The morphological evaluation of kidney by PAS staining after HFD fed in mice. (b) Detecting of macrophage makers F4/80 in mRNA level to determine invasion of macrophage into kidney in HFD mice. (c–e) The expression of relative markers in mRNA levels associated with M1-polarized macrophages in kidney of HFD-fed mice. (f–j) The analysis of markers of M2-polarized macrophages in mRNA level in kidney of HFD-fed mice. Data are shown as means ± s.e.m. (n = 8). *P < 0.05.

Mentions: HFD can also cause renal inflammation and hypofunction26. Renal structural changes were evaluated by histochemistry with the PAS stain after HFD. Clear and unbroken structures of renal sections were shown in both WT and Gpr97−/− chow-fed mice. There was also no interstitial fibrosis in the renal tubules or glomeruli. Mice fed the HFD exhibited renal injury, such as renal tubular epithelial cell cytoplasm vacuole degeneration, mesangial matrix expansion, and increased renal interstitial cells (Fig. 6a). However, the absence of Gpr97 did not impact upon the HFD-induced renal injury. In HFD-fed mice, a high inflammation status would increase renal injury and lipid metabolic disorder, and some inflammatory markers, such as TNF-α, IL-6, and MCP-1, were induced by the HFD2728. Next, we measured the alterations in renal inflammatory cytokines in HFD mice after Gpr97 knockout. In Gpr97-deficient HFD mice, there were more macrophages invading the kidney according to the increase in F4/80 mRNA levels (Fig. 6b). Meanwhile, the inflammatory factor TNF-α was increased in Gpr97−/− HFD mice compared with that in WT HFD mice (Fig. 6c), but there was no significant change in IL-1β and CD86 after Gpr97 knockout in HFD mice (Fig. 6d,e). So Gpr97 did not affect ratio of M1-polarized macrophages in kidney of HFD-fed mice. Further, we detected markers of M2- polarized macrophages including CD68, CD163, CD206, Arg1 and IL-10 in kidney and found increasing of those in kidney after Gpr97 deficiency in HFD-mice (Fig. 6f–j). According to our results, Gpr97 might be involved in the renal macrophage-inflammatory reaction and macrophage invasion in HFD mice, but not in the imbalance in the ratio of M1/M2 macrophages.


Gpr97 is dispensable for metabolic syndrome but is involved in macrophage inflammation in high-fat diet-induced obesity in mice.

Shi J, Zhang X, Wang S, Wang J, Du B, Wang Z, Liu M, Jiang W, Qian M, Ren H - Sci Rep (2016)

The HFD-induced inflammation analysis in kidney in the WT and Gpr97−/− mice.(a) The morphological evaluation of kidney by PAS staining after HFD fed in mice. (b) Detecting of macrophage makers F4/80 in mRNA level to determine invasion of macrophage into kidney in HFD mice. (c–e) The expression of relative markers in mRNA levels associated with M1-polarized macrophages in kidney of HFD-fed mice. (f–j) The analysis of markers of M2-polarized macrophages in mRNA level in kidney of HFD-fed mice. Data are shown as means ± s.e.m. (n = 8). *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835759&req=5

f6: The HFD-induced inflammation analysis in kidney in the WT and Gpr97−/− mice.(a) The morphological evaluation of kidney by PAS staining after HFD fed in mice. (b) Detecting of macrophage makers F4/80 in mRNA level to determine invasion of macrophage into kidney in HFD mice. (c–e) The expression of relative markers in mRNA levels associated with M1-polarized macrophages in kidney of HFD-fed mice. (f–j) The analysis of markers of M2-polarized macrophages in mRNA level in kidney of HFD-fed mice. Data are shown as means ± s.e.m. (n = 8). *P < 0.05.
Mentions: HFD can also cause renal inflammation and hypofunction26. Renal structural changes were evaluated by histochemistry with the PAS stain after HFD. Clear and unbroken structures of renal sections were shown in both WT and Gpr97−/− chow-fed mice. There was also no interstitial fibrosis in the renal tubules or glomeruli. Mice fed the HFD exhibited renal injury, such as renal tubular epithelial cell cytoplasm vacuole degeneration, mesangial matrix expansion, and increased renal interstitial cells (Fig. 6a). However, the absence of Gpr97 did not impact upon the HFD-induced renal injury. In HFD-fed mice, a high inflammation status would increase renal injury and lipid metabolic disorder, and some inflammatory markers, such as TNF-α, IL-6, and MCP-1, were induced by the HFD2728. Next, we measured the alterations in renal inflammatory cytokines in HFD mice after Gpr97 knockout. In Gpr97-deficient HFD mice, there were more macrophages invading the kidney according to the increase in F4/80 mRNA levels (Fig. 6b). Meanwhile, the inflammatory factor TNF-α was increased in Gpr97−/− HFD mice compared with that in WT HFD mice (Fig. 6c), but there was no significant change in IL-1β and CD86 after Gpr97 knockout in HFD mice (Fig. 6d,e). So Gpr97 did not affect ratio of M1-polarized macrophages in kidney of HFD-fed mice. Further, we detected markers of M2- polarized macrophages including CD68, CD163, CD206, Arg1 and IL-10 in kidney and found increasing of those in kidney after Gpr97 deficiency in HFD-mice (Fig. 6f–j). According to our results, Gpr97 might be involved in the renal macrophage-inflammatory reaction and macrophage invasion in HFD mice, but not in the imbalance in the ratio of M1/M2 macrophages.

Bottom Line: Gpr97 is highly expressed in some immunocytes, but its potential role in inflammatory regulation has not been revealed clearly.Furthermore, the levels of TNF-α were higher in the liver and kidney of Gpr97(-/-) HFD mice compared to those in wild-type HFD mice.The data indicate that Gpr97 might be required for local inflammation development in obesity-relative tissues, but does not play a role in metabolic disorder in HFD-induced obesity.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

ABSTRACT
Local inflammation in tissues is one of primary causes in development of metabolic disorder in obesity. The accumulation of macrophages in some tissues can induce inflammatory reactions in obesity. Gpr97 is highly expressed in some immunocytes, but its potential role in inflammatory regulation has not been revealed clearly. In our research, we investigated Gpr97 in regulating macrophage inflammation and metabolic dysfunction in the high-fat diet (HFD)-induced obese mice. The major metabolic phenotyping were not different after Gpr97 knockout in HFD-fed mice. Similar pathological alterations in adipose tissue, liver, and kidney were observed in Gpr97(-/-) HFD mice compared with WT-HFD mice. In white adipose tissue, loss of Gpr97 reduced the ratio of M1-macrophages and increased the M2-macrophage ratio, which was opposite to that seen in the wild-type HFD mice. More macrophages invaded in the liver and kidney after Gpr97 knockout in HFD mice. Furthermore, the levels of TNF-α were higher in the liver and kidney of Gpr97(-/-) HFD mice compared to those in wild-type HFD mice. The data indicate that Gpr97 might be required for local inflammation development in obesity-relative tissues, but does not play a role in metabolic disorder in HFD-induced obesity.

No MeSH data available.


Related in: MedlinePlus