BACKGROUNDObstructive sleep apnea hypopnea syndrome, characterized by chronic intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction. CIH has been identified to mediate mitochondrial damage in genioglossus. It has been reported that endoplasmic reticulum stress (ERS) could be induced by mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH-induced genioglossus injury, as well as the possible intervention effect of adiponectin (Ad) supplement in rats.

METHODSForty-five male Wistar rats were randomly divided into three groups and submitted to room air (group A, n=15) as a control or CIH (groups B and C, n=15, respectively). Throughout the exposure period, intravenous Ad was given in group C; while intravenous normal saline was simultaneously given in groups A and B. After 35-day exposure, genioglossus samples were obtained from the pentobarbital-anaesthetized rats via surgical dissection, following blood sampling. Western blotting was applied to detect expressions of ERS signals and associated apoptotic pathways in genioglossus. Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay (ELISA).

RESULTSSignificant hypoadiponectinemia was revealed in group B only (P < 0.05). Compared to those in groups A and C, expressions of markers involved in ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein 1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly enhanced in group B (all P < 0.01); while no significant difference was shown between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were remarkably activated in group B. The involved markers detected as the expression of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly elevated (all P < 0.01). Transvenous adiponectin supplement improved the above CIHinduced pathological changes in group C.

CONCLUSIONBeyond hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS-associated apoptotic pathways in genioglossus, which could be significantly improved by adiponectin supplement.

Adiponectin ; administration & dosage ; therapeutic use ; Animals ; Endoplasmic Reticulum Stress ; drug effects ; Hypoxia ; drug therapy ; physiopathology ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Sleep Apnea, Obstructive ; drug therapy

OBJECTIVETo establish a rabbit model of juvenile nonalcoholic steatohepatitis (NASH) for further study.

METHODSTwenty-eight New Zealand rabbit pups were fed with a high-fat diet (standard diet+10 % lard+2 % cholesterol) for 8 or 12 weeks as the two model groups, and 10 rabbits were fed with standard diet as the controls. Liver tissue samples were collected for Heamatoxylin-Eosin staining and pathological examination.

RESULTTypical histological hepatic lesions of NASH were observed in both model groups. Compared with control group, model groups showed a significant increase in serum ALT, AST, TG, TC levels (P <0.01), and decrease in serum adiponectin, IL-10 levels (P <0.05), meanwhile there was no significant difference between two model groups. TC and the degree of liver fatty infiltration were independent determinants of serum adiponectin level by stepwise multiple regression, beta=-1.33, P=0.006 and beta=-0.97, P=0.038, respectively, R square equal to 0.294.

CONCLUSIONThe juvenile steatohepatitis rabbit model has been established and the level of adiponectin can partly reflect the severity of liver steatosis.

Adiponectin ; blood ; Animals ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Fatty Liver ; blood ; metabolism ; pathology ; Female ; Interleukin-10 ; blood ; Male ; Rabbits ; Random Allocation

OBJECTIVETo investigate the role of adiponectin (ADP) and adiponectin receptor 2 (adipoR2) in pathology of fatty liver, and to investigate the effect of Chinese herbal decoction (Qushi Huayu Decoction, QHD) on fatty liver disease.

METHODSTwo experimental fatty liver models were used. One was induced with high-fat diet for ten weeks, and the rats were divided into normal, model and QHD group, the QHD group was administrated with QHD during the last four weeks. The other experimental fatty liver model was induced by subcutaneous injection of carbon tetrachloride (CCl4) in combination with high-fat and low-protein diet for four weeks, and the rats were also divided into normal, model and QHD group, the QHD group was administrated with QHD during the last two weeks. The observation items include: (1) hepatic steatosis (H.E. staining); (2) serum ADP, hepatic triglyceride (TG), free fatty acid (FFA) and adipoR2; (3) correlation among serum ADP content, hepatic TG, FFA and adipoR2.

RESULTS(1) Serious hepatic steatosis, increased hepatic TG and FFA, decreased serum ADP and hepatic adipoR2 were observed in the two models (P less than 0.01). QHD administration significantly reduced the hepatic TG and FFA, and increased serum ADP and hepatic adipoR2 (P less than 0.01) in these two models. (2) Inverse correlation was observed between hepatic TG, FFA and serum ADP, hepatic adipoR2 in these two models.

CONCLUSION(1) Decreased serum ADP and hepatic adipR2 may play important roles in pathological process of fatty liver. (2) QHD administration increased the serum ADP and hepatic adipoR2.

Adiponectin ; blood ; Animals ; Carbon Tetrachloride ; administration & dosage ; Dietary Fats ; administration & dosage ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fatty Acids, Nonesterified ; metabolism ; Fatty Liver ; drug therapy ; etiology ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Adiponectin ; metabolism ; Triglycerides ; metabolism

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1beta regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1beta, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1beta to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1beta each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1beta did not synergistically support the degradation of IkappaB-alpha or the nuclear translocation of NF-kappaB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-kappaB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1beta may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.
Adiponectin/administration & dosage/*metabolism ; *Arthritis, Rheumatoid/metabolism/pathology ; Cells, Cultured ; Cyclooxygenase 2/metabolism ; Gene Expression Regulation/drug effects ; Humans ; *Inflammation/metabolism/pathology ; Interleukin-1beta/administration & dosage/*metabolism ; Interleukin-6/metabolism ; Interleukin-8/metabolism ; Joints/metabolism/pathology ; Matrix Metalloproteinases ; NF-kappa B/metabolism ; Obesity/metabolism/pathology ; Osteoarthritis ; Receptors, Adiponectin/metabolism ; Receptors, Interleukin-1/metabolism ; *Synovial Fluid/cytology/metabolism

OBJECTIVETo evaluate the role of serum tumor necrosis factor-alpha (TNF-alpha) and adiponectin on insulin resistance in different fat diet rats.

METHODSThirty weanling female rats were randomly divided into 3 group (n = 10): a low-fat soybean oil (LFS; 22% of total energy fed as fat), high-fat soybean oil (HFS; 40% of total energy fed as fat), or high-fat soybean oil and swimming training at the same time (HFS + T). After fed for 10 weeks, the level of TNF-alpha, adiponectin in serum of rats were observed.

RESULTS(1) The body weight, percentage of body fat of HFS group increased compared with that of LFS group (P < 0.05), however those of HFS + T group were decreased (P < 0.05). (2) The level of serum insulin and ISI in HFS group were increased by LFS group (P < 0.05), in HFS+ T group the levels decreased. (3) And the serum level of TNF-alpha and IL-6 in HFS group were higher than those in LFS group (P < 0.05), the serum levels of adiponectin in HFS group were lower than those in LFS rats, and in HFS+ T group the levels of TNF-alpha and IL-6 were lower than those in HFS group (P < 0.05), the adiponectin level was higher than that in HFS group, and there were no significant difference between LFS group and HFS + T group.

CONCLUSIONExercises training could improve sugar and fat metabolism disorders, which also contributes to improving insulin resistance caused by high-fat diet.

Adiponectin ; blood ; Animals ; Diet, High-Fat ; adverse effects ; Dietary Fats ; administration & dosage ; Female ; Insulin ; blood ; Interleukin-6 ; blood ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDThe genioglossus (GG) is involved in the maintenance of an open airway for effective breathing. Although the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) was closely associated with GG dysfunction, its causes and possible treatment have not been elucidated. The aim of the study was to investigate the effects of chronic intermittent hypoxia (CIH) on serum adiponectin levels, electromyograph (EMG) activity and ultrastructure of GG, as well as the effect of an adiponectin supplement in anesthetized rats.

METHODSForty-two healthy male Wistar rats were randomly divided into normal control (A), CIH (B) and adiponectin treatment (C) groups, 14 rats in each group. CIH was performed eight hours per day for five weeks in both groups B and C. Group C received transvenous injection of adiponectin at the dosage of 10 microg per injection, twice a week for five weeks. At the end of the 5th week the GG EMG voltage was measured and compared among the three groups. Transmission electron microscope was used to observe the ultrastructure of the GG.

RESULTSCIH caused significant hypoadiponectinemia, weakened activity of GG EMG at both baseline and hypoxia stimulation, and induced ultrastructural pathological changes, such as, myofibril discontinuities, lysis of myofilament, edema of mitochondria and disruption of cristae, vacuolus and lysis of some mitochondria. Venous supplement of adiponectin improved the above pathological changes resulting from CIH.

CONCLUSIONCIH resulted in pathological changes in GG's EMG and ultrastructure, which could be improved by supplement of adiponectin and be associated with hypoadiponectinemia caused by CIH.

Adiponectin ; administration & dosage ; blood ; Animals ; Electromyography ; Hypoxia ; blood ; physiopathology ; Male ; Microscopy, Electron, Transmission ; Muscle, Skeletal ; physiology ; ultrastructure ; Random Allocation ; Rats ; Rats, Wistar ; Sleep Apnea, Obstructive ; blood ; physiopathology ; Tongue ; physiology ; ultrastructure

BACKGROUND/OBJECTIVES: Corn silk (CS) extract contains large amounts of maysin, which is a major flavonoid in CS. However, studies regarding the effect of CS extract on cholesterol metabolism is limited. Therefore, the purpose of this study was to determine the effect of CS extract on cholesterol metabolism in C57BL/6J mouse fed high-fat diets. MATERIALS/METHODS: Normal-fat group fed 7% fat diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS) group were orally administered CS extract (100 mg/kg body weight) daily. Serum and hepatic levels of total lipids, triglycerides, and total cholesterol as well as serum free fatty acid, glucose, and insulin levels were determined. The mRNA expression levels of acyl-CoA: cholesterol acyltransferase (ACAT), cholesterol 7-alpha hydroxylase (CYP7A1), farnesoid X receptor (FXR), lecithin cholesterol acyltransferase (LCAT), low-density lipoprotein receptor, 3-hyroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), adiponectin, leptin, and tumor necrosis factor α were determined. RESULTS: Oral administration of CS extract with HF improved serum glucose and insulin levels as well as attenuated HF-induced fatty liver. CS extracts significantly elevated mRNA expression levels of adipocytokines and reduced mRNA expression levels of HMG-CoA reductase, ACAT, and FXR. The mRNA expression levels of CYP7A1 and LCAT between the HF group and HFCS group were not statistically different. CONCLUSIONS: CS extract supplementation with a high-fat diet improves levels of adipocytokine secretion and glucose homeostasis. CS extract is also effective in decreasing the regulatory pool of hepatic cholesterol, in line with decreased blood and hepatic levels of cholesterol though modulation of mRNA expression levels of HMG-CoA reductase, ACAT, and FXR.
Adipokines ; Adiponectin ; Administration, Oral ; Animals ; Blood Glucose ; Cholesterol* ; Diet ; Diet, High-Fat* ; Fatty Liver ; Glucose ; Homeostasis ; Insulin ; Leptin ; Metabolism* ; Mice* ; Oxidoreductases ; Phosphatidylcholine-Sterol O-Acyltransferase ; Receptors, Lipoprotein ; RNA, Messenger ; Silk* ; Sterol O-Acyltransferase ; Triglycerides ; Tumor Necrosis Factor-alpha ; Zea mays*

OBJECTIVE: To explore the effect of niacin on the serum adiponectin concentration in hypercholesterolemia rabbit and the adiponectin concentration secreted by adipocytes in normal rabbits. METHODS: Ten male New Zealand white rabbits fed with high cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) The high cholesterol group maintained a high cholesterol diet for 8 weeks. (2) The same cholesterol diet plus niacin (0.4g/kg*d ) were administrated for 6 weeks in the niacin group. A control group was fed with normal diet for 14 weeks. Subcutaneous adipose from the control group was collected for adipocyte culture. Matured adipocytes were incubated with various concentrations of niacin (0, 0.25, 0.5, 1.0, and 2.0micromol/L). Adiponectin concentrations in the serum and adipocyte culture supernatant were measured by enzyme-linked-immunosorbent assay. RESULTS: Compared with the control group, rabbits in the high cholesterol group showed higher serum levels of total cholesterol, and low density lipoprotein cholesterol (LDL-C), all of which were significantly reduced by niacin treatment (P<0.01),and serum high density lipoprotein-cholesterol (HDL-C) significantly increased (P<0.01). At 8th week, the mean adiponectin concentration of rabbits fed with high cholesterol diet was significantly lower than that of the control group[(1.268+/-0.039)mg/L vs.(1.449+/-0.107)mg/L,P<0.01]. Niacin treatment significantly elevated the serum adiponectin level which was positively related to HDL-C,and negatively related to TC and LDL-C. Cell experiment in vitro indicated that niacin could significantly induce the adiponectin secretion of adipocytes in a dose-dependent manner. CONCLUSION Niacin can significantly promote the adiponectin secretion of adipocytes, suggesting that niacin probably has an ability of elevating the serum adiponectin level in addition to lipid-lowering effect.
Adipocytes ; cytology ; drug effects ; metabolism ; Adiponectin ; blood ; metabolism ; Animals ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; toxicity ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dose-Response Relationship, Drug ; Hypercholesterolemia ; blood ; etiology ; prevention & control ; Hypolipidemic Agents ; pharmacology ; Male ; Niacin ; pharmacology ; Rabbits ; Random Allocation

OBJECTIVESMetabolic syndrome (MS) in adolescents was reported to be closely associated with cardiovascular diseases in adulthood. However, no unified treatment measure for MS in adolescents is currently available. The aim of this study was to measure the changes of serum adiponectin levels, insulin sensitivity and other biochemical markers after metformin therapy in adolescents with MS, which might provide some information for set up a unified therapeutic measure for MS in adolescents.

METHODSIn this study, 348 moderately or severely obese adolescents and 24 non-obese healthy adolescents matched in age and sex were enrolled. The obese group included 208 males and 140 females aged from 7 to 16 years (11.5 +/- 2.1 years). Oral glucose tolerance test and biochemical markers measurement were done to all these subjects. Whole body insulin sensitivity index (WBISI), homeostasis model assessment-insulin resistance (HOMA-IR) and fasting serum adiponectin were compared among 36 adolescents with MS (who had two or three abnormalities of hyperglycosemia, hypertension or dyslipidemia), 61 simple obese subjects without abnormality of biochemical markers and 24 healthy controls. Moreover, the changes of WBISI, HOMA-IR and adiponectin levels in 20 cases with MS after metformin therapy for 3 months were measured.

RESULTS(1) HOMA-IR in control group (1.3), simple obese group (2.3) and MS group (4.9) increased by turns (F = 54.08, P < 0.001). WBISI and serum adiponectin in control group, simple obese group and MS group decreased by turns with significant difference [89.6, 22.8 and 10.7, F = 30.06; (7.1 +/- 2.6), (5.9 +/- 1.9), (2.8 +/- 0.9) mg/L, F = 64.93; P < 0.01 for all]. (2) HOMA-IR after metformin therapy decreased [5.7 (1.9-12.4) vs. 2.9 (0.9-7.4), t = 5.05, P < 0.01]; while the serum adiponectin levels increased with significant differences [(3.0 +/- 0.9) mg/L vs. (6.1 +/- 1.9) mg/L, t = 6.19, P < 0.01]. Systolic blood pressure [(132.4 +/- 7.5) mm Hg vs. (116.6 +/- 9.1) mm Hg, t = 8.36, P < 0.01], 2-hour glucose [(8.2 +/- 2.9) mmol/L vs. (5.3 +/- 1.0) mmol/L, t = 3.96, P < 0.01], triglyceride [(2.8 +/- 1.2) mmol/L vs. (1.3 +/- 0.9) mmol/L, t = 4.22, P < 0.01], total cholesterol [(4.9 +/- 0.6) mmol/L vs. (4.0 +/- 0.6) mmol/L, t = 4.72, P < 0.01], alanine aminotransferase [80.5 (29.0-286.0) U/L vs. 56.0 (23.0-163.0) U/L, t = 3.80, P < 0.01].

CONCLUSIONInsulin sensitivity in adolescents with MS was lower than that of simple obese group. Metformin can improve or ameliorate adiponectin levels, insulin sensitivity and some clinical markers.

Adiponectin ; blood ; secretion ; Adolescent ; Alanine Transaminase ; blood ; Blood Glucose ; drug effects ; Blood Pressure ; drug effects ; Case-Control Studies ; Child ; Cholesterol ; blood ; Fasting ; blood ; Female ; Homeostasis ; drug effects ; Humans ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Insulin ; blood ; secretion ; Male ; Metabolic Syndrome ; blood ; drug therapy ; metabolism ; Metformin ; administration & dosage ; pharmacology ; Obesity ; blood ; drug therapy ; metabolism ; Triglycerides ; blood

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 +/- 1.59 vs 5.12 +/- 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 +/- 11.3 vs 14.3 +/- 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).
Adiponectin/blood ; Aged ; Aged, 80 and over ; Atherosclerosis/complications/drug therapy ; Diabetes Mellitus, Type 2/complications/*drug therapy ; Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use ; Drug Administration Schedule ; Endothelium, Vascular/*drug effects/physiopathology ; Female ; Humans ; Male ; Middle Aged ; Nitroglycerin/therapeutic use ; Prospective Studies ; Pyrazines/pharmacology/*therapeutic use ; Regression Analysis ; Triazoles/pharmacology/*therapeutic use ; Vasodilation/drug effects ; Vasodilator Agents/therapeutic use