Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and a significant global health problem with substantial rise in prevalence over the last decades. It is becoming increasingly clear that NALFD is not only predominantly a hepatic manifestation of metabolic syndrome, but also involves extra-hepatic organs and regulatory pathways. Therapeutic options are limited for the treatment of NAFLD. Accordingly, a better understanding of the pathogenesis of NAFLD is critical for gaining new insight into the regulatory network of NAFLD and for identifying new targets for the prevention and treatment of NAFLD. In this review, we emphasize on the current understanding of the inter-organ crosstalk between the liver and peripheral organs that contributing to the pathogenesis of NAFLD.
Adipose Tissue ; pathology ; Animals ; Extracellular Vesicles ; metabolism ; Humans ; Hypothalamus ; metabolism ; Intestines ; microbiology ; pathology ; Non-alcoholic Fatty Liver Disease ; etiology ; metabolism ; microbiology ; pathology

Brown adipose tissue (BAT) plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue (WAT), have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BATactivation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.
Adipose Tissue, Brown ; metabolism ; Aging ; metabolism ; Animals ; Cachexia ; metabolism ; pathology ; Disease Models, Animal ; Energy Metabolism ; Humans ; Metabolic Syndrome ; metabolism ; Neoplasms ; metabolism ; pathology ; Obesity ; metabolism ; Thermogenesis

Obesity is characterized by abnormal and excessive adipose tissue accumulated in the body. Compared with peripheral obesity (the accumulation of subcutaneous adipose tissue), abdominal obesity (the accumulation of visceral adipose tissue) is associated with increased risk of the metabolic syndrome, such as diabetes, hypertension, atherosclerosis, and dyslipidemia. Adipose tissue is a highly heterogeneous endocrine organ. Adipose tissue depots differ significantly in anatomy, cell biology, glucose and lipid metabolism as well as in endocrine regulation. Visceral adipose tissue has a stronger metabolic activity and secrets a larger amount of free fat acids, adipocytokines, hormones and inflammatory factors, which flux into the liver directly via the hepatic portal vein. These characteristics indicate that visceral adiposity may lead to the metabolic syndrome and thus visceral adipose tissue might be the clinical target for the prevention and treatment of obesity.
Adipose Tissue ; pathology ; Humans ; Intra-Abdominal Fat ; pathology ; Lipid Metabolism ; Metabolic Syndrome ; physiopathology ; Obesity ; physiopathology ; Obesity, Abdominal ; physiopathology ; Subcutaneous Fat ; pathology

Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.
Adipose Tissue, Beige ; metabolism ; pathology ; Adipose Tissue, Brown ; metabolism ; pathology ; Animals ; Cell Line ; Energy Metabolism ; Humans ; Mice ; Obesity ; metabolism ; pathology ; therapy

OBJECTIVETo observe the effects of adipose-derived mesenchymal stem cells (ADSCs) with continous over-expression of glial cell line-derived neurotrophic factor (GDNF) on the motor function recovery and nerve regeneration of sciatic nerve of rats after electrical injury.

METHODSFive SD rats were collected to prepare ADSCs with over-expression of GDNF. One hundred and fifty SD rats were divided into normal control group (N), GDNF-ADSCs group (GA), ADSCs group (A), GDNF group (G), and physiological saline group (P) according to the random number table, with 30 rats in each group. Rats in group N were routinely fed without treatment, and rats in the other 4 groups were inflicted with electrical injury on sciatic nerve of thigh of the right hind leg. Rats in groups GA, A, G, and P were respectively injected with 100 µL suspension of ADSCs with over-expression of GDNF (1 x 10(7) cells per mL), 100 [µL ADSCs suspension (1 x 10(7) cells per mL), 100 µL GDNF solution (100 mg/L) , and 100 µL physiological saline to the surface of the injured nerves immediately after injury. Six rats of each group were collected for measuring hind limb stride from post injury week (PIW) 1 to 8, and morphology of the sciatic nerves was observed in PIW 8. In PIW 4, the protein expression of GDNF of sciatic nerves of the rest rats in each group was determined with Western blotting. Data were processed with one-way analysis of variance, analysis of variance of repeated measurement, and SNK test.

RESULTSCompared with that of group N, the hind limb stride values in groups GA, A, G, and P were significantly lower at each time point (with P values below 0.05). Compared with those of group P, the hind limb stride values in group GA from PIW 3 to 8, in group A in PIW 3, 5, and 7, and in group G in PIW 3, 5, 7, and 8 were significantly longer (with P values below 0.05). The hind limb stride values in group GA from PIW 4 to 8 were respectively (10.83 ± 0.97), (13.25 ± 1.40), (12.86 ± 1.42), (14.06 ± 1.50), and (15.09 ± 1.17) cm, which were significantly longer than those in group A [(8.90 ± 0.82), (9.03 ± 0.57), (9.27 ± 0.36), (9.86 ± 0.36), and (9.52 ± 0.58) cm] and group G [(8.87 ± 0.69), (8.51 ± 1.18), (9.34 ± 0.87), (9.76 ± 0.67), and (9.50 ± 1.22) cm], with P values below 0.05. Compared with that of group N, the number of myelinated nerve fibers of sciatic nerves was obviously decreased in group P but obviously increased in groups GA, A, and G; the diameter of axons was obviously shorter, and the myelin thickness was obviously increased in groups GA, A, G, and P in PIW 8 (with P values below 0.05). The number of myelinated nerve fibers in group GA was 31.2 ± 0.8, which was significantly higher than that in group A (23.7 ± 2.7), group G (22.3 ± 2.7), or group P (9.3 ± 2.8), with P values below 0.05. The diameter values of axons among groups P, A, G, and GA were similar (with P values above 0.05). The myelin thickness of rats in group GA was (3.41 ± 0.34) µm, which was significantly thicker than that in group A [(2.64 ± 0.37) µm] or group G [(2.41 ± 0.34) µm], with P values below 0.05. In PIW 4, the protein expression of GDNF of sciatic nerves was significantly higher in groups P, A, G, and GA than in group N (with P values below 0.05), and the protein expression of GDNF in group GA was significantly higher than that in group P, A, or G (with P values below 0.05).

CONCLUSIONSADSCs over-expressing GDNF protein can obviously promote the motor function recovery and nerve regeneration of sciatic nerve of rats after electrical injury.

Adipose Tissue ; Animals ; Electrophysiology ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; metabolism ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; metabolism ; Nerve Crush ; Nerve Regeneration ; physiology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; pathology ; physiology

INTRODUCTIONThe present study aimed to investigate the possible associations between serum levels of visfatin, an adipokine, and atherosclerosis in patients with ischaemic cerebrovascular disease.

METHODSA total of 95 participants were recruited for this study. Group A comprised 35 individuals with no history of cerebrovascular disease (control group) and Group B comprised 60 patients with ischaemic cerebrovascular disease. Group B was further categorised into two subgroups based on the ultrasonographic findings of the common carotid artery intima‑media thickness (CCA‑IMT) - Group B1 consisted of 21 patients with no atherosclerosis (i.e. CCA‑IMT ≤ 0.9 mm) and Group B2 consisted of 39 patients with atherosclerosis (i.e. CCA‑IMT > 0.9 mm). The body mass index, fasting blood total cholesterol, triglycerides, high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol and glucose levels of each patient were measured. Serum visfatin levels were determined using enzyme‑linked immunosorbent assays. Visfatin levels were compared between groups, and stepwise logistic regression analysis was used to identify risk factors for atherosclerosis, including visfatin levels.

RESULTSThe mean serum visfatin level of the patients in Group B was higher than that in Group A (75.5 ± 77.80 ng/mL vs. 8.6 ± 4.69 ng/mL; p < 0.05) and the level was higher in patients from Group B2 than those from Group B1 (89.0 ± 80.68 ng/mL vs. 50.4 ± 72.44 ng/mL; p < 0.05). Multivariate regression analysis showed that CCA‑IMT values were not significantly associated with visfatin levels. However, logistic regression analysis showed that serum visfatin was an independent risk factor for atherosclerosis (odds ratio 37.80; p = 0.004).

CONCLUSIONSerum visfatin may be an independent risk factor for cerebral infarction, as high serum visfatin levels are positively associated with the underlying pathogenic mechanisms of ischaemic cerebrovascular disease.

Adipokines ; metabolism ; Adipose Tissue ; pathology ; Adult ; Aged ; Atherosclerosis ; blood ; complications ; Body Mass Index ; Brain Ischemia ; blood ; complications ; Carotid Intima-Media Thickness ; Case-Control Studies ; Cerebrovascular Disorders ; blood ; complications ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Inflammation ; Logistic Models ; Male ; Middle Aged ; Nicotinamide Phosphoribosyltransferase ; blood ; Risk Factors

OBJECTIVETo investigate the effects of allogeneic adipose-derived stem cells (ADSCs) of rat on the early neovascularization of autologous fat transplantation.

METHODS(1) Experiment 1. Adipose tissue was collected from both inguinal regions of two SD rats to isolate, culture, and purify ADSCs through collagen enzyme digestion, density gradient centrifugation, and adherence method. The fourth passage of cells were collected for morphologic observation, detection of expressions of surface markers CD34, CD49d, CD106, and CD45 of ADSCs with flow cytometer, identification of adipogenic and osteogenic differentiation, and determination of the cell proliferation ability with thiazolyl blue method. (2) Experiment 2. Another 30 SD rats were divided into allogeneic adipose granule (AG) group (A, n = 6), autologous AG group (B, n = 8), autologous ADSCs+autologous AG group (C, n = 8), and allogeneic ADSCs+autologous AG group (D, n = 8) according to the random number table. The fourth passage of ADSCs were obtained from adipose tissue from one side of inguinal region of SD rats in group C. Adipose tissue obtained from one side of inguinal region of SD rats of the other 3 groups was abandoned. The AG was prepared from another side of inguinal region of SD rats in the 4 groups. The mixture of 0.6 g AG from one rat and 1 mL DMEM/F12 nutrient solution was injected subcutaneously into the back of another rat in group A, and so on. Autologous AG was injected into its own body of the rats in group B. The mixture of 1 mL autologous ADSCs mixture which contains 3.0 × 10⁶ cells per mililitre autologous ADSCs combined with autologous AG was injected into the rats in group C. The mixture of 1 mL allogeneic ADSCs mixture which contains 3.0 × 10⁶ cells per mililitre ADSCs extractived from the former 2 rats in experiment 1 combined with autologous AG was injected into the rats in group D. At 7 days post transplantation, fat transplants were harvested for gross observation, measurement of wet weight, pathological observation, and assessment of cells with positive expression of CD31 with immunohistochemical method. Data were processed with one-way analysis of variance and SNK test.

RESULTS(1) The fourth passage of cells proliferated well showing fusiform shape similar to fibroblasts. These cells showed positive expression of CD34 and CD49d and weak positive expression of CD106 and CD45. They were able to differentiate into adipocytes and osteoblasts. These cells were identified as ADSCs. The fourth passage of cells grew faster than that of the tenth passage. (2) At 7 days post transplantation, no liquifying necrosis or infection was observed in the fat transplants of the rats in the 4 groups. Wet weight of the fat transplants in groups A and B was respectively (0.25 ± 0.04) and (0.26 ± 0.03) g, which were less than those of groups C and D [(0.36 ± 0.03) and (0.35 ± 0.04) g, with P values below 0.05]. HE staining showed that there were less fat cells and more fibroblasts in the transplants of group A, visible fibrous tissue around uneven shape of fat cells in the transplants of group B, and almost identical size and shape of fat cells and unobvious fibrous tissues were found in the transplants of groups C and D. The cells with positive expression of CD31 were distributed in fibrous tissues in larger number but less around fat cells in the transplants of group A, while more of these cells were observed surrounding fat cells in the transplants of group B. There were more cells with positive expression of CD31 distributed surrounding fat cells in the transplants of groups C and D than that in group B. The cells with positive expression of CD31 observed under 400 times field were more in number in groups C (20.5 ± 1.1) and D (22.1 ± 1.0) than in groups A (8.0 ± 3.6) and B (10.9 ± 1.7), with P values below 0.05.

CONCLUSIONSAllogeneic ADSCs combined with autologous AG can significantly improve the early vascularization of fat transplantation as well as autologous ADSCs combined with autologous AG.

Adipocytes ; cytology ; transplantation ; Adipose Tissue ; blood supply ; cytology ; Animals ; Burns ; complications ; metabolism ; pathology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Neovascularization, Physiologic ; physiology ; Osteogenesis ; Rats ; Stem Cell Transplantation ; Stem Cells ; cytology ; physiology ; Transplantation, Autologous ; Wound Healing ; physiology

Ginsenoside Rb1 is an active component in ginseng. Previous in vitro experiments showed that ginsenoside Rb1, could inhibit lipolysis and promote glucose transporter in adipocytes. This study focused on the effect of ginsenoside Rb1 in insulin resistance and ectopic fat deposit in obese mice induced by high fat diet and its molecular mechanism. Obese male C57/L mice induced by high fat diet were randomly divided into the diet-induced obesity group (DIO group), the ginsenoside Rb1 group (Rb1 group) and the rosiglitazone group (Rog group), and continuously fed with high fat diet. In addition, male C57/L mice fed with normal diet were selected as the normal group (NC group). Mice in Rb1 group and Rog groups were intraperitoneally injected with ginsenoside Rb1 and rosiglitazone with the dosage of 20 mg x kg(-1) and 10 mg x kg(-1), respectively. NC and DIO groups were intraperitoneally injected with the same amount of saline. Two weeks later, the intraperitoneal glucose tolerance test (IPGTT) was performed. Three days later, the mice were killed, and their serum samples were collected to detect insulin and free fatty acid (FFA). Their livers were weighed to examine the triglyceride content, and a pathological detection was performed. Epididymal adipose tissues were weighed, and PDE3B, HSL and perilipin were detected by Western blotting. The results showed that the treatment with ginsenoside Rb1 for two weeks could improve the glucose tolerance of obese mice. Except for 0-120 min, the areas under the glucose tolerance curve (0-30 min, 0-60 min and 0-90 min) in the Rb1 group were less than that in the DIO group (P < 0.05, n = 5), with a much lower HOMA-IR (P < 0.05, n = 5). The fat level of obese mice was significantly reduced by Rbl (P < 0.05, n = 5), and so were liver weight/weight (P < 0.05, n = 8). The increased serum FFA of obese mice declined after the treatment of Rb1 (P < 0.05, n = 8). Rb1 could partially recover the expression of perilipin in adipose tissues, but without obvious change in the expressions of PDE3B and HSL and the phosphorylated activation. The above findings indicated that ginsenoside Rb1 could reduce the release of FFA and alleviate the ectopic deposit of triglyceride by up-regulating the expression of perilipin in adipose tissue, which may be one of its mechanisms for improving the insulin resistance and abnormal glucose metabolism of organisms.
Adipose Tissue ; drug effects ; pathology ; Animals ; Body Weight ; drug effects ; Diet, High-Fat ; adverse effects ; Dose-Response Relationship, Drug ; Fatty Acids, Nonesterified ; blood ; Gene Expression Regulation ; drug effects ; Ginsenosides ; pharmacology ; Glucose Tolerance Test ; Insulin ; blood ; Insulin Resistance ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity ; blood ; etiology ; metabolism ; pathology ; Organ Size ; drug effects ; Triglycerides ; metabolism

OBJECTIVETo investigate the effect of adipose-derived stem cells (ADSC) on renal injury in mice with burn injury and sepsis and its underlying mechanism.

METHODS(1) Adipose tissue was collected from both inguinal regions of 5 C57BL/6J mice to isolate, culture and purify ADSC through enzyme digestion, density gradient centrifugation, and adherence method. Cells of the third passage were used in the experiment. The morphologic change in cells was observed and the growth curve of cells was determined. The expression of cell surface antigen phenotype was analyzed by flow cytometry, and the cells were identified by adipogenic and osteogenic differentiation. (2) Another 37 C57BL/6J mice were divided into normal control group (n = 5), saline group (n = 16), and group ADSC (n = 16) according to the random number table. The mice in saline group and group ADSC were injected with Pseudomonas aeruginosa after being subjected to 15% TBSA full-thickness burn on the back to reproduce septic burn model. Then the mice were injected with saline and ADSC through tail vein respectively. At post burn hour (PBH) 12, 24, 48, and 72, the pathological change in kidney tissue was observed, the levels of blood urea nitrogen and serum creatinine were determined, and the levels of TNF-α, IL-12, IL-10, and cyclooxygenase-2 (COX2) mRNA were determined with real-time fluorescence quantitative PCR in both groups. Above-mentioned indexes were also examined in the normal control group (without burn). Data were processed with multifactor analysis of variance and LSD- t test.

RESULTS(1) Cells in the third passage were orderly arranged with the shape similar to fibroblasts. The percentages of CD90(+), CD105(+), CD34(-), and CD45(-) cells were all above 90%. The cells could differentiate into osteoblasts and adipocytes. The cells were identified to be ADSC. (2) From PBH 12 to PBH 72, the neutrophil infiltration gradually increased, and the structure of kidney tubules and glomeruli were deranged in saline group. The pathological change in kidney tissue in group ADSC was less serious than that of normal control group at each time point. From PBH 12 to PBH 72, the levels of blood urea nitrogen and serum creatinine in saline group were significantly higher than those of normal control group and group ADSC (P values all below 0.01). Compared with those of the normal control group, the levels of TNF-α and IL-12 mRNA were higher in group ADSC and saline group at PBH 24 (P values all below 0.05). At PBH 24, the level of TNF-α mRNA in group ADSC (1.58 ± 0.19) was lower than that of saline group (3.36 ± 0.30, P < 0.05). At PBH 24, the levels of IL-10 and COX2 mRNA in group ADSC (2.89 ± 0.47, 4.90 ± 0.59) were higher than those in normal control group (1.00 ± 0.15, 1.00 ± 0.27) and saline group (1.32 ± 0.38, 1.57 ± 0.38, P values all below 0.05).

CONCLUSIONSADSC can decrease the levels of blood urea nitrogen and serum creatinine, promote the production of anti-inflammatory cytokines IL-10 and COX2, and reduce the release of the pro-inflammatory cytokines TNF-α and IL-12 to offer protective effects against renal injury in burn mice with sepsis.

Adipose Tissue ; cytology ; Animals ; Burns ; complications ; metabolism ; pathology ; Creatine ; blood ; Cyclooxygenase 2 ; metabolism ; Disease Models, Animal ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Kidney ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Nitrogen ; blood ; Sepsis ; etiology ; metabolism ; pathology ; Stem Cells ; cytology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the role of the expression of PPAR-gamma gene in the adipogenesis in hemangioma evolution.

METHODSRoutine immunohistochemistry staining of Perilipin A, the marker antigen of adipocytes, was performed to observe the adipogenesis in hemangioma. Immunofluorescence staining of PPAR-gamma, the important transcription factor in promoting adipogenesis, was carried out to observe its location in hemangioma tissue, with the co-staining of alpha-SMA and CD31. And RT-PCR was used to examine the expression of PPAR-gamma gene in hemangioma in different stages.

RESULTSIn the evolution of hemangioma, the number of adipocytes increased continuously. And the tumor was replaced by fibrofatty tissue finally. PPAR-gamma was located in the nuclei of perivascular cell in hemangioma tissue. The expression of PPAR-gamma gene in hemangioma increased in the evolution of hemangioma, but still was lower than that in normal fat tissue from children.

CONCLUSIONThe expression of PPAR-gamma in the perivascular cells suggests that they may contribute to the adipogenesis in hemangioma involution.

Adipogenesis ; Adipose Tissue ; metabolism ; pathology ; Hemangioma ; metabolism ; pathology ; Humans ; PPAR gamma ; metabolism