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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

Detection of macrophages polarization in white adipose tissue (WAT) in HFD mice.(a) Hematoxylin and eosin staining of WAT sections of WT and Gpr97−/− mice. Pictures were captured at 40× under optical microscope. (b) The expression of the relative factor associated with total macrophages F4/80 in mRNA levels in WAT. (c–f) The expression of relative factors in mRNA levels associated with M1-polarized macrophages in WAT. (g–k) The expression of relative factors associated with M2-polarized macrophages in WAT. Data are shown as means ± s.e.m. (n = 8). 0.01 < P < 0.05, ***P < 0.01.
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f3: Detection of macrophages polarization in white adipose tissue (WAT) in HFD mice.(a) Hematoxylin and eosin staining of WAT sections of WT and Gpr97−/− mice. Pictures were captured at 40× under optical microscope. (b) The expression of the relative factor associated with total macrophages F4/80 in mRNA levels in WAT. (c–f) The expression of relative factors in mRNA levels associated with M1-polarized macrophages in WAT. (g–k) The expression of relative factors associated with M2-polarized macrophages in WAT. Data are shown as means ± s.e.m. (n = 8). 0.01 < P < 0.05, ***P < 0.01.

Mentions: White adipose tissue (WAT), which is a critical regulator of adiposity and energy metabolism, has been found to undergo metabolic changes during a high-fat diet22. Adipocyte hypertrophy and hyperplasia occurs in HFD-induced obesity, including overgrowth of WAT23. In our results, hypertrophy of WAT was a typical change in HFD mice, but the morphology of WAT did not significantly alter between WT and Gpr97−/− HFD mice (Fig. 3a). It has been reported that the HFD will result in the accumulation of macrophage in WAT, which can lead to inflammation24. According to the alteration in the mRNA level of the macrophage marker F4/80, we found that Gpr97 deficiency can cause a reduction in macrophage invasion of WAT in HFD-fed mice (Fig. 3b). The general view of the inflammatory reactions in WAT is an imbalance in the ratio of M1/M2 macrophages24. We analyzed the relative mRNA expression of cytokines associated with M1- and M2-polarized macrophages to confirm the function of Gpr97 in M1/M2 polarization of WAT macrophages. The M1-polarized-related parameters TNF-α, IL-6, IL-1β and CD86 displayed a decrease in Gpr97−/− HFD mice compared to WT HFD mice (Fig. 3c–f). Meanwhile, the M2-polarized-related parameters, including CD68, CD163, CD206, Arg1 and IL-10 were increased in Gpr97−/− HFD mice (Fig. 3g–k). The accumulation of M1 “pro-inflammatory” macrophages and the reduction of M2 “anti-inflammatory” macrophages in white adipose tissue can lead to adipose tissue dysfunction24. We found that Gpr97 deficiency can reverse this imbalance of M1/M2 macrophages in WAT. In Gpr97−/− HFD mice, M2 macrophages were increased and M1 macrophages were decreased obviously, which indicate that Gpr97 might contribute to the local inflammatory reactions charged of M1-macrophages. In the obesity induced by HFD, loss of Gpr97 will cause opposite imbalance of M1/M2 and reduce levels of inflammatory cytokines in WAT of mice.


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)

Detection of macrophages polarization in white adipose tissue (WAT) in HFD mice.(a) Hematoxylin and eosin staining of WAT sections of WT and Gpr97−/− mice. Pictures were captured at 40× under optical microscope. (b) The expression of the relative factor associated with total macrophages F4/80 in mRNA levels in WAT. (c–f) The expression of relative factors in mRNA levels associated with M1-polarized macrophages in WAT. (g–k) The expression of relative factors associated with M2-polarized macrophages in WAT. Data are shown as means ± s.e.m. (n = 8). 0.01 < P < 0.05, ***P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Detection of macrophages polarization in white adipose tissue (WAT) in HFD mice.(a) Hematoxylin and eosin staining of WAT sections of WT and Gpr97−/− mice. Pictures were captured at 40× under optical microscope. (b) The expression of the relative factor associated with total macrophages F4/80 in mRNA levels in WAT. (c–f) The expression of relative factors in mRNA levels associated with M1-polarized macrophages in WAT. (g–k) The expression of relative factors associated with M2-polarized macrophages in WAT. Data are shown as means ± s.e.m. (n = 8). 0.01 < P < 0.05, ***P < 0.01.
Mentions: White adipose tissue (WAT), which is a critical regulator of adiposity and energy metabolism, has been found to undergo metabolic changes during a high-fat diet22. Adipocyte hypertrophy and hyperplasia occurs in HFD-induced obesity, including overgrowth of WAT23. In our results, hypertrophy of WAT was a typical change in HFD mice, but the morphology of WAT did not significantly alter between WT and Gpr97−/− HFD mice (Fig. 3a). It has been reported that the HFD will result in the accumulation of macrophage in WAT, which can lead to inflammation24. According to the alteration in the mRNA level of the macrophage marker F4/80, we found that Gpr97 deficiency can cause a reduction in macrophage invasion of WAT in HFD-fed mice (Fig. 3b). The general view of the inflammatory reactions in WAT is an imbalance in the ratio of M1/M2 macrophages24. We analyzed the relative mRNA expression of cytokines associated with M1- and M2-polarized macrophages to confirm the function of Gpr97 in M1/M2 polarization of WAT macrophages. The M1-polarized-related parameters TNF-α, IL-6, IL-1β and CD86 displayed a decrease in Gpr97−/− HFD mice compared to WT HFD mice (Fig. 3c–f). Meanwhile, the M2-polarized-related parameters, including CD68, CD163, CD206, Arg1 and IL-10 were increased in Gpr97−/− HFD mice (Fig. 3g–k). The accumulation of M1 “pro-inflammatory” macrophages and the reduction of M2 “anti-inflammatory” macrophages in white adipose tissue can lead to adipose tissue dysfunction24. We found that Gpr97 deficiency can reverse this imbalance of M1/M2 macrophages in WAT. In Gpr97−/− HFD mice, M2 macrophages were increased and M1 macrophages were decreased obviously, which indicate that Gpr97 might contribute to the local inflammatory reactions charged of M1-macrophages. In the obesity induced by HFD, loss of Gpr97 will cause opposite imbalance of M1/M2 and reduce levels of inflammatory cytokines in WAT of mice.

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