Physiological and pathological roles of mast cells in adipose tissue

Mast cells are important cells for the innate immunity that reside in tissues including adipose tissue and are involved in various physiological and pathological processes by producing a range of biological mediators. Adipose tissue not only acts as an energy depot and regulator of energy homeostasis that can deposit excess energy and dissipate energy through heat, but also is an active endocrine organ capable of producing hormones and adipokines. The dysfunction of adipose tissue is highly correlated with metabolic disorders, such as obesity, type 2 diabetes mellitus and so on. This review focuses on the physiological and pathological roles of mast cells in adipose tissue.     

Research progress and important scientific issues of organ fibrosis

Organ fibrosis is a common pathogenetic change of parenchymal organs under chronic conditions, characterized by increased fibrous connective tissues and reduced parenchymal cells. The essence of renal fibrosis is the "repair of scars" after renal tissue damage. It involves a loss of renal parenchyma cells, activation of myofibroblasts, deposition of extracellular matrix, imbalance of metabolism and abnormal interactions with organs. Hepatic fibrosis is a kind of repair response induced by various chronic hepatic diseases, including viral hepatitis and metabolic liver disease, and it is the common pathological basis of end-stage hepatic disease. Pulmonary fibrosis is a progressive and fatal inflammatory interstitial lung disease, characterized by inflammatory destruction and extracellular matrix deposition. Myocardial fibrosis is a process of pathological repair after a variety of injuries caused by hypertension, hypertrophic cardiomyopathy, viral cardiomyopathy, valve disorders, myocardial ischemia, diabetes, obesity and other metabolic abnormalities. Organ fibrosis indicates some common pathogenesis, but the exact mechanisms differ from organs and still need further investigation to identify biomarkers for early diagnosis and to devise drugs specifically for fibrosis. This article comprehensively summarizes the recent developments in organ fibrosis over the last 3 years, including underlying mechanisms and urgent scientific issues remained.     

Hemangioblastic characteristics of human adipose tissue-derived adult stem cells in vivo

AIM: To investigate whether Flk1+CD31-CD34- cells isolated from human adult adipose tissue have characteristics of hemangioblasts in vivo. METHODS: After sublethally irradiated (300cGy) with a caesium source, the female non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice were injected with human adipose tissue-derived Flk1+CD31-CD34- cells (105 cells per mouse) via tail vain with 0.4 mL Roswell Park Memorial Institute medium (RPMI-1640). The control mice received the same volume of RPMI-1640 medium. All mice were killed 2 months after transplantation for further study. The differentiation potential of Flk1+CD31-CD34- cells was assessed in bone marrow and gastrointestinal tract by the methods of flow cytometry, RT-PCR, FISH, and triple-color immunofluorescence. RESULTS: Flk1+CD31-CD34- human adipose tissue-derived adult stem cells differentiated into endothelial cells and hematopoietic cells at the single-cell level in vivo. CONCLUSION: Human adult adipose tissue-derived Flk1+CD31-CD34- cells bear characteristics of hemangioblast in vivo and may have potential application for the treatment of hematopoietic and vascular diseases.     

Advance in function of Eph-ephrin bidirectional signaling

Erythropoietin-producing hepatocyte (Eph) receptor, a membrane-bound protein tyrosine kinase receptor, plays the function of bidirectional signal transduction by binding to the membrane-tethered ephrin ligands on the neighboring cells. New findings reveal that Eph-ephrin bidirectional transduction of signals plays roles in embryonic deve-lopment and the physiological metabolism of adult organs, and its dysfunction is involved in a variety of pathological processes, such as cell adhesion and separation, angiogenesis, nerve growth and remodeling, bone remodeling, tumorigenesis and development, immune and metabolic diseases. Therefore, in-depth study of Eph-ephrin is of great significance for understanding the pathophysiological mechanisms and treatment of diseases. This review discusses the progress in Eph-ephrin bidirectional signal transduction system.     

Transplantation of exogenous adipose tissue derived mesenchymal stem cells for treatment of acute myocardial infarction in rat

AIM: To establish a method of isolating,culturing the adipose tissue-derived mesenchymal stem cells in vitro and to investigate the possibility of exogenous transplanting the adipose tissue derived mesenchymal stem cells for treatment of rat acute myocardial infarction.METHODS: 18 male rats were separated randomly into 3 groups: sham surgery group (control,n=6),acute myocardial infarction control group (AMI,n=6) and myocardial infarction plus cell transplantation group (AMI+cell,n=6).The infarcted hearts were made by occlusion of left coronary artery.The mesenchymal stem cells were isolated from the rats’ peritoneum by using digestion methods and reproduced in vitro,then the cells were labeled with BrdU and implanted into the infarcted heart of the rats.Heart functions were measured 4 weeks after implantation.The hearts were also harvested for pathological and histoimmunochemical observations to determine the survival and location of the implanted cells.RESULTS: Plenty of mesenchymal stem cells were obtained from the adipose tissue of rats’ peritoneum.Compared with the AMI group,the left ventricular systolic pressure in the cell therapy group was increased significantly (P<0.01),the left ventricular end-diastolic pressure was decreased (P<0.01),and the ratio of the left ventricular pressure rise and decay (±dp/dt) was decreased (P<0.05).The number of blood vessels was increased at the boundary of infarction site by pathological observation.The labeled cells were founded in the infarcted myocardium and the blood vessel wall.CONCLUSION: The adipose tissue is a new optional stem cell source.The methods of exogenous transplantation of adipose tissue derived mesenchymal stem cells for treatment of AMI is effective and feasible.     

Role of FAT/CD36 in high-fat diet-induced adipose tissue inflammation

AIM: To investigate the role of fatty acid translocase/CD36 (FAT/CD36) in adipose tissue inflammation induced by a high-fat diet. METHODS: C57BL/6J mice were fed with a normal-chow diet (NCD) or a high-fat diet (HFD) for 14 weeks. The content of free fatty acid (FFA) in the serum was measured by ELISA. The expression of CD36, cytokines and chemokines at mRNA and protein levels in the adipose tissues was determined by real-time polymerase chain reaction and Western blotting. Immunohistochemical staining was used to examine the macrophages infiltration in the adipose tissues. The inflammatory responses in CD36 knockout mice and wild type mice with high-fat diet were analyzed. RESULTS: The levels of FAT/CD36 were higher in HFD group than that in NCD group. HFD feeding enhanced the mRNA and protein expression of IL-1β, IL-6, TNF-α, MCP-1 and MIP-1, as well as promoted macrophage infiltration in the adipose tissues. Interestingly, as fed with HFD, the expression of cytokines/chemokines and macrophage infiltration were significantly reduced in adipose tissues of the CD36 knockout mice, compared with the wild type mice. CONCLUSION: High-fat diet promotes adipose tissue inflammation in the mice in a FAT/CD36-dependent manner.     

Role of intestinal microbiota-farnesoid X receptor axis in metabolic diseases

Intestinal microbiota is associated with metabolic diseases such as obesity, nonalcoholic fatty liver disease and insulin resistance. Farnesoid X receptor (FXR), also known as bile acid receptor, is a typical nuclear receptor, which is involved in the regulation of bile acid and glycolipid metabolism. Intestinal microbiota regulates FXR activity by affecting bile acid composition, where bile acid hydrolase plays an important role. Recent studies have found that intestinal microbiota affects the development of metabolic diseases through regulating the FXR, and the intestinal microbiota-FXR axis may be an ideal drug target for metabolic diseases.     

Improvement of insulin sensitivity by osteocalcin inhibits inflammation in the adipose tissue of obese mice

AIM: To explore the improving effect of osteocalcin on obesity-related insulin resistance and inflammation in the adipose tissue of obese mice.METHODS: The C57BL/6 mice were fed with high-fat diet for 12 weeks to obtain obese mice. Osteocalcin (30 ng/kg or 3 ng/kg) and saline solution (control) were intraperitoneally injected for other 4 weeks. The fat mass, body weight, serum triglycerides and serum free fatty acid were analyzed. Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Macrophage infiltration degree in the adipose tissue was observed by immunohistochemical staining. The mRNA expression of monocyte chemotactic protein-1 (MCP-1) and CD68 was detected by real-time fluorescence quantitative PCR.RESULTS: Osteocalcin (30 ng/kg or 3 ng/kg) treatment for 4 weeks significantly reduced the body weight, fat mass and insulin level, and improved abnormal glucose tolerance and insulin resistance in the obese mice. Moreover, the macrophage infiltration decreased, and the mRNA expression of MCP-1 and CD68 was down-regulated in the adipose tissue of obese mice treated with osteocalcin at 30 ng/kg.CONCLUSION: Osteocalcin at 30 ng/kg significantly reduces body weight and fat mass, and attenuates the severity of insulin resistance through down-regulating the mRNA expression of MCP-1 and CD68 and inbihiting macrophage infiltration in the adipose tissue of obese mice induced by high-fat diet.     

Basic research and clinical significance of chromogranin A

Chromogranin A (CGA) has been considered as the most useful indicator of neuroendocrine activity. It is the precursor of many biologically active peptides produced by proteolytic cleavage, which play their roles in a large variety of patterns in different tissue. Clinically, CGA is of diagnostic and evaluation value in several diseases. The protein structure, biological and physiological functions as well as the clinical significance of CGA are reviewed in this article.     

Role of type II innate lymphoid cells in browning of white adipose tissue

Type II innate lymphoid cells (ILC2s) are widely distributed in the blood, intestines, trachea, lung, spleen, liver, animal fat and skin, and involved in the innate immune responses. ILC2s have attracted much attention for its important roles in the conversion of white adipose to beige adipose. Studies have shown that ILC2s are essential for the proliferation and differentiation of adipocyte precursor cells, and they also play a vital role in anti-parasitic infection and allergic inflammation. This review discusses the discovery, differentiation, development, distribution and function of ILC2s, and their relationships with the browning of white adipose tissue for providing valuable references on understanding the pathogenesis, prevention and treatment of obesity and fat metabolism disorders.     

Role of AMP-activated protein kinase in fibrogenesis

Fibrosis is a common clinical disease that occurs in a variety of organs, and mainly manifests increased connective tissue of organ tissue and decreased parenchymal cells. Continuous progression may lead to organ structural damage, dysfunction and even depletion, seriously threatening human health and life safety. Therefore, in-depth study of the pathogenesis of fibrosis and the development of effective therapeutic drugs are of great importance for the prevention and treatment of fibrosis. Recent studies provide evidence that AMP-activated protein kinase (AMPK) plays an important role in the development of fibrosis. In combination with related literatures, this paper reviews the structure and biological function of AMPK, AMPK in inflammatory response associated with fibrosis, epithelial-mesenchymal transition, extracellular matrix and myofibroblasts, and the therapeutic role of AMPK as a new target in treating fibrosis diseases.     

Effect of high fat diet on UCP2 mRNA expression in white adipose tissue of SR-A I/II gene knock-out mice

AIM:To observe the relationship between UCP2 mRNA expression in white adipose tissue and diet-induced obesity in SR-A I/II gene knock-out (SR-AⅠ/Ⅱ-/-) mice. METHODS:Fluorescent quantitative RT-PCR was used to detect UCP2 mRNA expression in mice epididymal white adipose tissue. The cellular morphological changes were analyzed by using image analysis. Serum TG, TC and LDL-C concentrations were measured by enzymatic determination. RESULTS:After fed with high fat diet for 12 weeks, average body weight of SR-A I/II-/- mice was much higher than that of wild type (SR-A I/II+/+) control mice (P<0.01), as well as the serum lipid (TG, TC, LDL-C) levels, epididymal fat pad weight, adipocyte area and diameter. UCP2 mRNA expression in white adipose tissue in SR-A I/II-/- mice was significant lower than that in SR-A I/II+/+ control mice (P<0.01). CONCLUSION:Abnormal UCP2 mRNA expression may be associated with SR-A I/II-/- mice susceptive to diet-induced obesity.     

Advances in research on mechanism of CCN proteins in prevention and treatment of obesity and non-alcoholic fatty liver

CCN protein family plays a role in regulating the formation and remodeling of extracellular matrix, inflammation regulation, injury repair and so on, which is closely related to the occurrence and development of metabolic diseases. This review focuses on the mechanism of CCN proteins in obesity and non-alcoholic fatty liver. The roles of CCN proteins in the adipocyte activation, the fibrosis and inflammatory response in non-alcoholic fatty liver, and the injury repair against non-alcoholic fatty liver and its complications are introduced, providing new ideas for the study of CCN proteins in metabolic diseases such as obesity and non-alcoholic fatty liver.     

Effect of high-fructose diet on adipose tissue renin-angiotensin system in rats

AIM: To observe the effects of high-fructose diet on adipose tissue inflammation and renin-angiotensin system (RAS), and to reveal the role of Toll-like receptor 2 (TLR2) in this process.METHODS: Male SD rats (n=16) were randomly divided into control group, high fructose group, high fructose+siRNA negative control group, and high fructose+TLR2-siRNA group. The rats in control group were fed with a standard chow diet. The rats in high fructose group were fed with a diet with 60% fructose, and the rats in high fructose+TLR2-siRNA group and high fructose+siRNA negative control group were transfected with TLR2 siRNA and scrambled siRNA, respectively. Serum uric acid was measured and visceral adipose tissue was weighed at the 14th week. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), angiotensinogen (AGT), and angiotensin Ⅱ (Ang Ⅱ) were measured by ELISA. Infiltrating macrophages in the adipose tissues were measured with immunohistochemistry. The mRNA expression of IL-6, TNF-α, monocyte chemoattractant protein-1 (MCP-1), AGT, angiotensin-converting enzyme 1 (ACE1), angiotensin Ⅱ type 1 receptor (AT1R), and angiotensin Ⅱ type 2 receptor (AT2R) was detected by RT-qPCR. The protein level of TLR2 was determined by Western blot.RESULTS: High fructose-fed rats showed elevated serum uric acid, raising fat content, higher serum concentrations of IL-6, TNF-α, AGT and AngⅡ, and more infiltrating macrophages in the adipose tissues (P<0.05). Moreover, the mRNA levels of IL-6, TNF-α,MCP-1, AGT, ACE1, AT1R and AT2R in the adipose tissues were increased (P<0.05). When high fructose-fed rats were transfected with TLR2-siRNA, the dramatic decreases in TLR2 protein level and number of infiltrating macrophages in the adipose tissues were found. Both in serum and adipose tissues, the mRNA levels of inflammatory cytokines and RAS components were all significantly decreased (P<0.05).CONCLUSION: High-fructose diet up-regulates RAS in adipose tissues via activation of TLR2 inflammation signaling pathway.     

Protective effect of adiponectin on glucose and lipid metabolism by suppressing MHCⅡ expression

AIM: To investigate whether the protective effect of adiponectin on glucose and lipid metabolism is achieved through down-regulating major histocompatibility complex class Ⅱ (MHCⅡ) in the adipose tissue. METHODS: Adiponectin knockout (KO) mice and C57BL/6(WT) mice were fed with high-fat diet and standard diet for 24 weeks, respectively. The body weight, fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic histology, and class Ⅱ trans-activator (CⅡTA), histocompatibility 2 class Ⅱ antigen E beta (H2-Eb1) and cluster of differentiation 74(CD74) mRNA and MHC Ⅱ protein levels in adipose tissue were measured at sacrifice. siRNA targeting MHC Ⅱ and overexpression vector was used in 3T3-L1 cells to explore the effect of adiponectin on the protein level of MHCⅡ. RESULTS: The levels of body weight, FBG, FINS, HOMA-IR, TC, TG, LDL-C, hepatic steatosis, CⅡTA, H2-Eb1 and CD74 mRNA expression, and MHCⅡ protein expression in the KO mice were higher than those in the WT mice that fed with high-fat diet or standard diet. In 3T3-L1 cells, inhibition of adiponectin reversed MHC Ⅱ protein level induced by specific siRNA. The expression of MHC Ⅱ in adipocytes decreased after adiponectin was overexpressed. CONCLUSION: Adiponectin improves glucose and lipid metabolism through suppressing the expression of MHCⅡ in the adipose tissue.     

Effect of glycine on body weight and lipid metabolism in mice

AIM: To study the effect of glycine on body weight and lipid metabolism in mice. METHODS: Mice were randomly divided into four groups, control, high-fat diet group (HF), glycine group (Gly), and glycine treatment group (Gly+HF). The mice were fed with normal diet and high-fat diet for 12 days, respectively, and then were treated with glycine solution by intraperitoneal injection. Finally, the serum was collected to measure serum lipid, epididymal fat-pads, pararenal fat-pads and abdominal fat-pads were taken out to weight. Moreover, pathologic changes in liver were observed. RESULTS: The body weight of HF group was obviously lower than that in control; the body weight and adipose tissue content of Gly group were obviously lower than those in control; the body weight and adipose tissue content of Gly+HF group were obviously lower than those in HF group; the levels of TC and TG in Gly group were obviously lower than those in control; there was no statistical difference in serum lipid between Gly+HF and HF groups. In addition, marked hepatic steatosis in HF group, and slight hepatic steatosis in Gly+HF group were found. CONCLUSION: Gly can decrease the body weight and adipose tissue content and serum lipid in normal diet and high-fat diet mice, and it also can prevent hepatic steatosis.     

Progress of P-selectin glycoprotein ligand-1 in kidney diseases

P-selectin glycoprotein ligand-1 (PSGL-1) is an adhesion molecule mainly expressed on the surface of leukocytes and platelets, which plays a vital part in immune recognition, inflammatory response and thrombosis. The prevalence of chronic kidney disease (CKD) is increased gradually and it has been one of major diseases that threaten the world's public health. In addition, its etiology is complicated, and most of the pathogenesis is incompletely understood. Researches show that PSGL-1 participates in the development of kidney diseases in a variety of ways, and its mechanism may involve signaling pathways such as TGF-β1/Smad and PI3K/AKT/GSK-3β, as well as key renal regulators such as connective tissue growth factor and chemokine (C-C motif) ligand 2. This review summarizes the research progress of PSGL-1 in renal fibrosis, lupus nephritis, obesity-related kidney disease and acute kidney injury.