OBJECTIVETo study the effects of Jiaotai Pill (JTP) and its single components on ectopic fat accumulation in rats with type 2 diabetes mellitus (T2DM).

METHODSThe T2DM model of rat was established by injection of streptozotocin from tail vein and high fat-caloric diet feeding. Model rats were randomly divided into the model group and four treated groups were treated respectively with JTP and its single components, Rhizoma Coptidis, Cinnamon and metformin, via gastric perfusion. Meanwhile, a normal control group was also set up. Body weight (BW), liver index (LI), levels of fasting plasma glucose (FPG), fasting serum insulin (FINS) and insulin resistance index (HOMA-IR), plasma activities of liver associated enzymes (LAE), triglyceride (TG) contents and pathological changes of liver, heart and muscle were determined before and after a 8-week treatment.

RESULTSAs compared with the normal rats, BW, LI, LAE activities, HOMA-IR, TG contents of the liver, heart and muscle were all increased in the model rats (P<0.05 or P<0.01), with pathologic appearance of fatty degeneration in different degrees. Compared with the model group, LI, LAE, HOMA-IR, and TG contents in the liver, heart and muscle tissues were decreased in different extents in the four treated groups (P<0.05 or P<0.01), and the histology of tissues in them was restored to near normal. Compared with the metformin treated group, the hepatic and muscular TG contents decreased in the JTP treated group (P<0.01), and the muscular TG content in the Rhizoma Coptidis treated group were lower (P<0.05). And the gamma-GT level in the JTP treated group was the lowest in the three Chinese drugs treated groups (P<0.01).

CONCLUSIONSThe disturbances of glucose and lipid metabolism and abnormality of liver function in T2DM rats could be improved by JTP and its single components. The mechanism might be related to their effects in improving insulin resistance and reducing ectopic fat accumulation.

Adiposity ; drug effects ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Insulin Resistance ; Intra-Abdominal Fat ; pathology ; Lipid Metabolism ; drug effects ; Liver ; pathology ; Male ; Muscle, Skeletal ; metabolism ; Phytotherapy ; Rats ; Rats, Wistar

Adiposity ; drug effects ; Animals ; Diethylhexyl Phthalate ; toxicity ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Male ; Maternal Exposure ; Metabolic Diseases ; chemically induced ; PPAR gamma ; genetics ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley

PURPOSE: Although the presence of cannabinoid type 1 (CB1) receptor in islets has been reported, the major contributor to the protective effect of rimonabant on islet morphology is unknown. We determined whether the protective effect of rimonabant on pancreatic islet morphology is valid in established diabetes and also whether any effect was independent of decreased food intake. MATERIALS AND METHODS: After diabetes was confirmed, Otsuka Long-Evans Tokushima Fatty rats, aged 32 weeks, were treated with rimonabant (30 mg/kg/d, rimonabant group) for 6 weeks. Metabolic profiles and islet morphology of rats treated with rimonabant were compared with those of controls without treatment (control group), a pair-fed control group, and rats treated with rosiglitazone (4 mg/kg/d, rosiglitazone group). RESULTS: Compared to the control group, rats treated with rimonabant exhibited reduced glycated albumin levels (p<0.001), islet fibrosis (p<0.01), and improved glucose tolerance (p<0.05), with no differences from the pair-fed control group. The retroperitoneal adipose tissue mass was lower in the rimonabant group than those of the pair-fed control and rosiglitazone groups (p<0.05). Rimonabant, pair-fed control, and rosiglitazone groups showed decreased insulin resistance and increased adiponectin, with no differences between the rimonabant and pair-fed control groups. CONCLUSION: Rimonabant had a protective effect on islet morphology in vivo even in established diabetes. However, the protective effect was also reproduced by pair-feeding. Thus, the results of this study did not support the significance of islet CB1 receptors in islet protection with rimonabant in established obesity-associated type 2 diabetes.
Adiponectin/metabolism ; Adiposity/drug effects ; Animals ; Cell Proliferation/drug effects ; Diabetes Mellitus, Type 2/diet therapy/*drug therapy ; Eating/*drug effects ; Glucose Intolerance/diet therapy/*drug therapy ; Insulin Resistance ; Insulin-Secreting Cells/*drug effects/pathology ; Male ; Piperidines/adverse effects/*therapeutic use ; Pyrazoles/adverse effects/*therapeutic use ; Rats ; Rats, Inbred OLETF ; Receptor, Cannabinoid, CB1/physiology ; Thiazolidinediones/*therapeutic use

OBJECTIVETo investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).

METHODS30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured.

RESULTSSignificant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05).

CONCLUSIONOur results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

Adipose Tissue, Brown ; drug effects ; Adiposity ; drug effects ; Animals ; Dietary Fats ; administration & dosage ; pharmacology ; Ion Channels ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondrial Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Triglycerides ; chemistry ; pharmacology ; Uncoupling Protein 1 ; Weight Loss

OBJECTIVETo investigate the effect of immunization with prokaryotically expressed recombinant fusion protein of extracellular near-transmembrane domain of Tibet minipig leptin receptor (OBR) on fat deposition in SD rats.

METHODSA pair of specific primers containing BamHI and HindIII restriction enzyme sites was designed to amplify the extracellular near-transmembrane domain (1705-2364 bp) of Tibet minipig OBR gene. After digestion, the amplified fragment was inserted into the plasmid pRSETA between BamHI and HindIII sites. The recombinant plasmid was transformed and expressed in E.coli BL21(DE3) and the product was analyzed by SDS-PAGE and Western blotting. SD rats were immunized with the fusion protein, and the changes in body weight, feed intake, body length, Lee's index, percentage of abdominal fat, liver fat deposition and subcutaneous fat deposition were assessed.

RESULTSThe recombinant fusion protein obtained (about 27.6 kD) was expressed in E.coli induced by IPTG and identified by SDS-PAGE and Western blotting. The rats immunized with the fusion protein showed no significant changes in body weight, body length, Lee's index, percentage of abdominal fat or liver fat deposition as compared with the control rats. Nevertheless, the immunization caused significantly increased feed intake and significantly decreased volume of subcutaneous fat cells.

CONCLUSIONImmunization with the fusion protein of extracellular near-transmembrane domain of Tibet minipig OBR can promote feed intake and suppress subcutaneous fat deposition in SD rats.

Adiposity ; drug effects ; Animals ; Base Sequence ; Female ; Gene Expression ; Genetic Vectors ; Obesity ; Plasmids ; Rats ; Rats, Sprague-Dawley ; Receptors, Leptin ; administration & dosage ; genetics ; Recombinant Fusion Proteins ; administration & dosage ; genetics ; Subcutaneous Fat ; physiology ; Swine ; Swine, Miniature

OBJECTIVETo investigate the antiobesity effect of Jueming Prescription (JMP), a Chinese herbal medicine formula, and its influence on mRNA expressions of beta3 adrenergic receptor (beta3-AR) and uncoupling protein-2 (UCP-2) in adipose tissue of diet-induced obese rats.

METHODSFifty male Sprague-Dawley rats were randomly divided into the normal control group (n =8) that was on a standard chow diet, and the obese model group (n =42) that was on a diet of high fat chow. Two weeks after the high fat diet, 29 obese rats in the obese model group were further randomly divided into 3 groups: the untreated obese model group (n =9), the metformin group (n =10, metformin 300 mg kg⁻¹ day)⁻¹, and the JMP group (n =10, JMP 4 g kg⁻¹ day⁻¹). After 8-week treatment, body weight, wet weight of visceral fat, and percentage of body fat (PBF) were measured. The levels of fasting blood glucose, serum lipids, and insulin were assessed, and insulin sensitivity index (ISI) was calculated. The adipose tissue section was stained with hematoxylin-Eosin, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expressions of beta3-AR and UCP-2 from the peri-renal fat tissue were determined by real-time reverse transcription polymerase chain reaction (RT-PCR).

RESULTSCompared with the obese model group, treatment with JMP resulted in significantly lower body weight, wet weight of visceral fat, PBF, and diameter of adipocytes, and significantly higher level of high-density lipoprotein cholesterol, ISI (all P<0.01), JMP increased the mRNA expressions of beta3-AR and UCP-2 from perirenal fat tissue (P <0.05, P<0.01).

CONCLUSIONSJMP could reduce body weight and adipocyte size; and the effect was associated with the up-regulation of beta3-AR and UCP-2 expressions in the adipose tissue and improvement of insulin sensitivity.

Adipocytes ; drug effects ; metabolism ; pathology ; Adiposity ; drug effects ; Animals ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Cell Size ; drug effects ; Diet, High-Fat ; Drugs, Chinese Herbal ; pharmacology ; Epididymis ; drug effects ; pathology ; Fasting ; blood ; Gene Expression Regulation ; drug effects ; Insulin ; blood ; Intra-Abdominal Fat ; drug effects ; metabolism ; pathology ; Ion Channels ; genetics ; metabolism ; Lipids ; blood ; Male ; Mitochondrial Proteins ; genetics ; metabolism ; Obesity ; blood ; genetics ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Adrenergic, beta-3 ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Uncoupling Protein 2 ; Weight Loss ; drug effects

Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF-/- mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF-/- mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF-/- mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF-/- mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF-/- improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases.
3T3-L1 Cells ; Adipocytes/drug effects/metabolism ; Adiposity/*genetics ; Animals ; B-Cell Activating Factor/*genetics ; Cells, Cultured ; Culture Media, Conditioned/pharmacology ; Diet, High-Fat ; Disease Models, Animal ; Gene Knockout Techniques ; Inflammation/*genetics ; Lipogenesis/genetics ; Macrophages/metabolism ; Male ; Mice ; Mice, Knockout ; Obesity/*etiology