TREM-1 Associated Macrophage Polarization Plays a Significant Role in Inducing Insulin Resistance in the Obese Population

Subramanian, Saravanan; Agrawal, Swati; Pallati, Pradeep K.; Sharma, Poonam; Agrawal, Devendra K.; Nandipati, Kalyana C.

doi:10.21203/rs.3.rs-44070/v1

Cited by 3 publications

(6 citation statements)

References 39 publications

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“…The elevation of TREM‐1 in liver with steatosis or steatohepatitis could at least partly due to the excessive liver influx of FAs. Previous studies reported that TREM‐1 could be a common stress response of hepatocytes to various insults, such as inflammation and lipid accumulation . Therefore, we speculated that TREM‐1 may attribute to inflammation and lipid accumulation during NAFLD development.…”

Section: Discussionmentioning

confidence: 91%

“…Phosphorylation of Jak2 activated downstream of the signal transducer and activator of transcription 3/5 phosphorylation, which enhanced NF‐κB activity and an increase of NF‐κB subunits P50/P65, finally augmented expression of inflammatory factors . Subramanian et al indicated that abnormal TREM‐1 expression was found in liver tissues of obese diabetic and nondiabetic patients. Zhou et al found that inhibition of TREM‐1 can inhibit inflammation and the occurrence of colon tumors.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of TREM‐1 attenuates inflammation and lipid accumulation in diet‐induced nonalcoholic fatty liver disease

Huang

Shen

et al. 2019

J of Cellular Biochemistry

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In the liver tissues of obese diabetic or nondiabetic patients, triggering receptor expressed on myeloid cells-1 (TREM-1) is usually found to be upregulated, thus leading to upregulation of various inflammatory cytokines and lipid accumulation. On the other hand, nonalcoholic fatty liver disease (NAFLD), characterized by excess lipid accumulation, and inflammatory injury in liver, is becoming an epidemic disease, globally. In the present study, we aimed to investigate the biological role and the underlying mechanisms of TREM-1 in NAFLD. upregulation of TREM-1 occurred in high-fat diet (HFD)-induced mice NAFLD model and oleic acid-treated HepG2 and primary mouse hepatocytes cell model at messenger RNA and protein levels. Functional studies established that overexpression of TREM-1 displayed hyperlipidemia, and increased in inflammatory indicators and lipid accumulationrelated genes, which was ameliorated by knockdown of TREM-1. Our results also showed that obvious lipid accumulation and inflammatory injury occurred in the liver tissue of HFD-fed mice, while treatment with lentiviral vector short hairpin TREM showed marked improvement in tissue morphology and architecture and less lipid accumulation, thus deciphering the mechanism through which knockdown of TREM-1 ameliorated the inflammatory response and lipid accumulation of NAFLD mice through inactivation of the nuclear factor-κB (NF-κB) and PI3K/AKT signal pathways, respectively. In conclusion, TREM-1/NF-κB and TREM-1/PI3K/AKT axis could be an important mechanism in ameliorating the inflammatory response and lipid accumulation, respectively, thus shedding light on the development of novel therapeutics to the treatment of NAFLD.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Inhibition of TREM‐1 attenuates inflammation and lipid accumulation in diet‐induced nonalcoholic fatty liver disease

Huang

Shen

et al. 2019

J of Cellular Biochemistry

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“…Therefore, we used CD45 low CD11b + CD86 + as a marker of M1 microglia and CD45 low CD11b + CD206 + as a marker of M2 microglia. CD11b + and CD45 high are general markers of macrophages, and CD86 and CD206 are markers of M1‐ and M2‐like macrophages, respectively . Therefore, CD45 high CD11b + CD86 + was used as a marker of M1 macrophages and CD45 high CD11b + CD206 + as a marker of M2 macrophages (Supplementary Table 1).…”

Section: Methodsmentioning

confidence: 99%

Immune changes in peripheral blood and hematoma of patients with intracerebral hemorrhage

Jiang

Wang

et al. 2020

FASEB j.

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Immunologic changes in the hematoma of patients with intracerebral hemorrhage (ICH) and the contribution of these changes to prognosis are unknown. We collected the blood samples and hematoma fluid from 35 patients with acute ICH (<30 hours from symptom onset) and 55 age-matched healthy controls. Using flow cytometry and ELISA, we found that the percentages of granulocytes, regulatory T cells, helper T (Th) 17 cells, and dendritic cells were higher in the peripheral blood of patients with ICH than in healthy controls, whereas the percentages of lymphocytes, M1-like macrophages, and M2-like macrophages were lower. Levels of IL-6, IL-17, IL-23, TNF-α, IL-4, IL-10, and TGF-β were higher in the peripheral blood of patients with ICH. The absolute counts of white blood cells, lymphocytes, monocytes, and granulocytes in the hematoma tended to be greater at 12-30 hours than they were within 12 hours after ICH, but the percentage of Th cells decreased in peripheral blood.Increased levels of IL-10 in the serum and hematoma, and a reduction in M1-like macrophages in hematoma were independently associated with favorable outcome on day 90. These results indicate that immunocytes present in the hematoma may participate in the acute-phase inflammatory response after ICH. K E Y W O R D Shematoma, immune changes, intracerebral hemorrhage, outcome, patients | 2775 JIANG et Al.

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“…Recent data show that TREM2 plays a protective role in the pathogenesis and etiology of obesity-induced insulin resistance. [40][41][42] The expression of M2 macrophage markers and TREM2 was downregulated in omentum, subcutaneous, and liver biopsy samples of the obese subjects. [40][41][42] Liu et al found that TREM2−/− mice underwent HFD displayed elevated fat accumulation, less macrophage infiltration, and enhanced inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

“…[40][41][42] The expression of M2 macrophage markers and TREM2 was downregulated in omentum, subcutaneous, and liver biopsy samples of the obese subjects. [40][41][42] Liu et al found that TREM2−/− mice underwent HFD displayed elevated fat accumulation, less macrophage infiltration, and enhanced inflammatory response. 43 Interestingly, TREM2expressing macrophages in metabolic diseases had recently been reported.…”

Section: Discussionmentioning

confidence: 99%

Emodin inhibits lipid accumulation and inflammation in adipose tissue of high‐fat diet‐fed mice by inducing M2 polarization of adipose tissue macrophages

Peng

et al. 2021

The FASEB Journal

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Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti‐inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high‐fat diet (HFD)‐induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD‐fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin‐treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin‐induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.

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TREM-1 Associated Macrophage Polarization Plays a Significant Role in Inducing Insulin Resistance in the Obese Population

Cited by 3 publications

References 39 publications

Inhibition of TREM‐1 attenuates inflammation and lipid accumulation in diet‐induced nonalcoholic fatty liver disease

Inhibition of TREM‐1 attenuates inflammation and lipid accumulation in diet‐induced nonalcoholic fatty liver disease

Immune changes in peripheral blood and hematoma of patients with intracerebral hemorrhage

Emodin inhibits lipid accumulation and inflammation in adipose tissue of high‐fat diet‐fed mice by inducing M2 polarization of adipose tissue macrophages

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