scholarly journals Adipose Tissue SIRT1 Regulates Insulin Sensitizing and Anti-Inflammatory Effects of Berberine

2020 ◽  
Vol 11 ◽  
Author(s):  
Yun Shan ◽  
Shuchen Zhang ◽  
Bin Gao ◽  
Shu Liang ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Glucose Consumption ◽  
Adenosine Monophosphate ◽  
Serum Concentrations ◽  
Coptis Chinensis ◽  
Akt Phosphorylation ◽  
Ampk Pathway ◽  
Metabolic Dysregulation ◽  
Anti Inflammatory

Berberine (BBR), which is an active component of Coptis chinensis Franch, has been reported to improve glucose metabolism and insulin resistance in animal and human studies, predominantly via activation of the 5′-adenosine monophosphate kinase (AMPK) pathway and suppression of the inflammation response. However, the mechanisms underlying the effects of BBR on AMPK and inflammation remain unclear. In this present study, we found that BBR upregulated SIRT1 expression in 3T3L-1 adipocytes and adipose tissue. Inhibition of SIRT1 blunted the BBR-induced increase in glucose consumption and uptake in adipocytes. The BBR-induced activation of the AMPK pathway and AKT phosphorylation in adipocytes and adipose tissue were also attenuated by inhibition or knockout of Sirt1. The BBR-induced improvement of systemic insulin sensitivity was impaired by Sirt1 knockout in HFD-induced obese mice. The suppressing effects of BBR on systemic and local inflammatory responses, such as serum concentrations and expression of inflammatory cytokines, phosphorylation of c-Jun N-terminal kinase (JNK) and IKKβ, and the accumulation of F4/80-positive macrophages in adipose tissue were also attenuated in Sirt1 knockout mice. The BBR-induced decrease in PGC-1α acetylation was reversed by inhibition or knockout of Sirt1 in adipocytes and adipose tissue. Together, these results indicate that adipose tissue SIRT1 is a key regulator of the insulin sensitizing and anti-inflammatory effects of BBR, which contributes to the improvement of metabolic dysregulation.

scholarly journals Biological and pathophysiological role of adiponectin

2019 ◽  
Vol 10 (2) ◽  
pp. 83-87
Author(s):  
Yury V. Petrenko ◽  
Ksenia S. Gerasimova ◽  
Valeria P. Novikova
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Biological Activities ◽  
Normal Weight ◽  
Blood Levels ◽  
High Concentration ◽  
Obese People ◽  
Adipoq Gene ◽  
Wide Range ◽  
Anti Inflammatory

Adipose tissue is now recognized as an important endocrine organ that secretes numerous protein hormones, including leptin, adiponectin, and resistin. Adiponectin is a hormone that is produced by white adipose tissue. Adiponectin has been isolated independently by several groups of scientists. In humans, this protein is encoded by the ADIPOQ gene. Adiponectin receptors are widely distributed in many organs and tissues including liver, heart, pancreas, kidneys, muscles and many other cell types. A serum concentration of adipocin correlates with body mass index (BMI). Decreased level of adiponectin leads to obesity, the development of gestational complications in pregnant women, as well as a high risk of diabetes mellitus development and atherosclerosis. A high concentration of this hormone has anti-inflammatory, antiatherogenic, antiproliferative and cancer-defense mechanisms. Adiponectin strongly suppresses hepatic gluconeogenesis by inhibiting genes involved in glucose production. Obese people have lower blood levels of adiponectin than normal weight individuals. Adiponectin’s anti-inflammatory and anti-apoptotic properties result in protection of the blood vessels, heart, lungs, and colon. Adiponectin, an abundant adipocyte-secreted factor with a wide-range of biological activities, improves insulin sensitivity in insulin target tissues, modulates inflammatory responses, and plays a crucial role in the regulation of energy metabolism.

scholarly journals Cell-extrinsic autophagy in mature adipocytes regulates anti-inflammatory response to intestinal tissue injury through lipid mobilization

2021 ◽  
Author(s):  
Felix Clemens Richter ◽  
Matthias Friedrich ◽  
Mathilde Pohin ◽  
Ghada Alsaleh ◽  
Irina Guschina ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Protective Effects ◽  
Adipose Tissue Macrophages ◽  
Anti Inflammatory ◽  
Major Nutrients

Autophagy is a critical cellular recycling pathway which is genetically linked to the development of intestinal inflammation in humans. Inflammation drives adipose tissue breakdown and provision of major nutrients such as free fatty acids (FFA). However, the effect of autophagy-mediated FFA release by adipocytes in immune-mediated inflammatory diseases remains unexplored. In a mouse model of intestinal inflammation, we found that visceral adipocytes upregulate autophagy at peak inflammation. Adipocyte-specific loss of the key autophagy gene Atg7 (Atg7Ad) resulted in the exacerbation of intestinal inflammation. TNFα-induced lipolysis was impaired in Atg7-deficient adipocytes leading to the reduced availability of several FFA species, and decreased expression of the FFA transporter CD36 on adipose tissue macrophages (ATMs). Visceral adipose tissues from Atg7Ad mice released less IL-10 resulting in lower levels of circulating IL-10 in colitis. ATMs present the main source of adipose tissue-derived IL-10 during colitis. In vitro assays confirmed that FFA restriction from macrophages reduced CD36 expression and diminished IL-10 production. Taken together, our study demonstrates that autophagy-mediated FFA release from adipocytes directs anti-inflammatory responses in ATMs, which in turn conveys protective effects for distant intestinal inflammation.

scholarly journals Functional Food Targeting the Regulation of Obesity-Induced Inflammatory Responses and Pathologies

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Shizuka Hirai ◽  
Nobuyuki Takahashi ◽  
Tsuyoshi Goto ◽  
Shan Lin ◽  
Taku Uemura ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Amino Terminal ◽  
Inflammatory State ◽  
Anti Inflammatory

Obesity is associated with a low-grade systemic chronic inflammatory state, characterized by the abnormal production of pro- and anti-inflammatory adipocytokines. It has been found that immune cells such as macrophages can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. Obesity-induced inflammation is considered a potential mechanism linking obesity to its related pathologies, such as insulin resistance, cardiovascular diseases, type-2 diabetes, and some immune disorders. Therefore, targeting obesity-related inflammatory components may be a useful strategy to prevent or ameliorate the development of such obesity-related diseases. It has been shown that several food components can modulate inflammatory responses in adipose tissue via various mechanisms, some of which are dependent on peroxisome proliferator-activated receptorγ(PPARγ), whereas others are independent on PPARγ, by attenuating signals of nuclear factor-κB (NF-κB) and/or c-Jun amino-terminal kinase (JNK). In this review, we introduce the beneficial effects of anti-inflammatory phytochemicals that can help prevent obesity-induced inflammatory responses and pathologies.

scholarly journals The Anti-Inflammatory Effect ofPrunus yedoensisBark Extract on Adipose Tissue in Diet-Induced Obese Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Hee Kang ◽  
Tae-Kyung Kwak ◽  
Bo-Geun Kim ◽  
Kyung-Jin Lee
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Receptor Gene ◽  
Fasting Blood Glucose ◽  
Scavenger Receptor ◽  
Receptor Expression ◽  
Bark Extract ◽  
Epididymal Adipose Tissue ◽  
Low Grade ◽  
Anti Inflammatory

Chronic, low-grade inflammatory responses occur in obese adipose tissue and play a crucial role in the development of insulin resistance. Macrophages exposed to high glucose upregulate the expression of SRA, a macrophage-specific scavenger receptor. The present study investigated whetherPrunus yedoensis(PY) bark extract affects the inflammatory response and scavenger receptor gene expression observed in a diet-induced obesity modelin vivo. Oral administration of PY extract significantly reduced fasting blood glucose levels without a change in body weight in mice fed a high fat diet for 17 weeks. PY extract significantly suppressed expression of inflammatory and macrophage genes such as tumor necrosis factor-α, interleukin-6, and F4/80 in epididymal adipose tissue. Among scavenger receptor genes, SRA expression was significantly reduced. The inhibitory responses of PY extract and its fractions were determined through evaluation of scavenger receptor expression in THP-1 cells. PY extract and its ethyl acetate fraction decreased the levels of SRA mRNA and phospho-ERK1/2 during monocyte differentiation. Our data indicate that the anti-inflammatory effects of PY extract and its downregulation of SRA seem to account for its hypoglycemic effects.

scholarly journals Flavonoids: Nutraceuticals for Rheumatic Diseases via Targeting of Inflammasome Activation

2021 ◽  
Vol 22 (2) ◽  
pp. 488
Author(s):  
Young-Su Yi
Keyword(s):  
Rheumatic Diseases ◽  
Fruits And Vegetables ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cellular Damage ◽  
Inflammatory Rheumatic Diseases ◽  
Inflammasome Activation ◽  
Central Feature ◽  
Inflammatory Protein ◽  
Anti Inflammatory

Inflammation, an innate immune response that prevents cellular damage caused by pathogens, consists of two successive mechanisms, namely priming and triggering. While priming is an inflammation-preparation step, triggering is an inflammation-activation step, and the central feature of triggering is the activation of inflammasomes and intracellular inflammatory protein complexes. Flavonoids are natural phenolic compounds predominantly present in plants, fruits, and vegetables and are known to possess strong anti-inflammatory activities. The anti-inflammatory activity of flavonoids has long been demonstrated, with the main focus on the priming mechanisms, while increasing numbers of recent studies have redirected the research focus on the triggering step, and studies have reported that flavonoids inhibit inflammatory responses and diseases by targeting inflammasome activation. Rheumatic diseases are systemic inflammatory and autoimmune diseases that primarily affect joints and connective tissues, and they are associated with numerous deleterious effects. Here, we discuss the emerging literature on the ameliorative role of flavonoids targeting inflammasome activation in inflammatory rheumatic diseases.

scholarly journals Extracellular Vesicles Do Not Mediate the Anti-Inflammatory Actions of Mouse-Derived Adipose Tissue Mesenchymal Stem Cells Secretome

2021 ◽  
Vol 22 (3) ◽  
pp. 1375
Author(s):  
María Carmen Carceller ◽  
María Isabel Guillén ◽  
María Luisa Gil ◽  
María José Alcaraz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Toll Like Receptor 4 ◽  
Anti Inflammatory ◽  
Phagocytic Response

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.

scholarly journals Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lu Wang ◽  
Yafei Rao ◽  
Xiali Liu ◽  
Liya Sun ◽  
Jiameng Gong ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Lung Inflammation ◽  
Respiratory Diseases ◽  
Inflammatory Responses ◽  
The Other ◽  
Target Cells ◽  
Administration Route ◽  
Toll Like Receptor ◽  
Administration Routes ◽  
Anti Inflammatory

Abstract Background Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined. Results In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not. Conclusion The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

scholarly journals Luteolin transforms the polarity of bone marrow-derived macrophages to regulate the cytokine storm

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shuxia Wang ◽  
Shuhang Xu ◽  
Jing Zhou ◽  
Li Zhang ◽  
Xiaodong Mao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Responses ◽  
Bone Marrow Cells ◽  
Membrane Surface ◽  
Inflammatory Factors ◽  
Mouse Bone Marrow ◽  
Macrophage Polarisation ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
M1 Type

Abstract Background Macrophages are indispensable regulators of inflammatory responses. Macrophage polarisation and their secreted inflammatory factors have an association with the outcome of inflammation. Luteolin, a flavonoid abundant in plants, has anti-inflammatory activity, but whether luteolin can manipulate M1/M2 polarisation of bone marrow-derived macrophages (BMDMs) to suppress inflammation is still unclear. This study aimed to observe the effects of luteolin on the polarity of BMDMs derived from C57BL/6 mice and the expression of inflammatory factors, to explore the mechanism by which luteolin regulates the BMDM polarity. Methods M1-polarised BMDMs were induced by lipopolysaccharide (LPS) + interferon (IFN)-γ and M2-polarisation were stimulated with interleukin (IL)-4. BMDM morphology and phagocytosis were observed by laser confocal microscopy; levels of BMDM differentiation and cluster of differentiation (CD)11c or CD206 on the membrane surface were assessed by flow cytometry (FCM); mRNA and protein levels of M1/M2-type inflammatory factors were performed by qPCR and ELISA, respectively; and the expression of p-STAT1 and p-STAT6 protein pathways was detected by Western-blotting. Results The isolated mouse bone marrow cells were successfully differentiated into BMDMs, LPS + IFN-γ induced BMDM M1-phenotype polarisation, and IL-4 induced M2-phenotype polarisation. After M1-polarised BMDMs were treated with luteolin, the phagocytosis of M1-polarized BMDMs was reduced, and the M1-type pro-inflammatory factors including IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and CD86 were downregulated while the M2-type anti-inflammatory factors including IL-10, IL-13, found in inflammatory zone (FIZZ)1, Arginase (Arg)1 and CD206 were upregulated. Additionally, the expression of M1-type surface marker CD11c decreased. Nevertheless, the M2-type marker CD206 increased; and the levels of inflammatory signalling proteins phosphorylated signal transducer and activator of transcription (p-STAT)1 and p-STAT6 were attenuated and enhanced, respectively. Conclusions Our study suggests that luteolin may transform BMDM polarity through p-STAT1/6 to regulate the expression of inflammatory mediators, thereby inhibiting inflammation. Naturally occurring luteolin holds promise as an anti-inflammatory and immunomodulatory agent.

scholarly journals IL4-10 Fusion Protein Shows DMOAD Activity in a Rat Osteoarthritis Model

Cartilage ◽  
2021 ◽  
pp. 194760352110267
Author(s):  
E.M. van Helvoort ◽  
H.M. de Visser ◽  
F.P.J.G. Lafeber ◽  
K. Coeleveld ◽  
S. Versteeg ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Single Molecule ◽  
Mechanical Allodynia ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Synovial Inflammation ◽  
Interleukin 4 ◽  
Analgesic Effects ◽  
Metabolic Dysregulation ◽  
Anti Inflammatory

Objective Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation. Design rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats ( n = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP ( n = 10) or phosphate buffered saline (PBS; n = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test. Results Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration ( P = 0.042) and decreased mechanical allodynia ( P < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP. Conclusion rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.

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