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OBJECTIVES@#To explore the mechanism of Chinese medicine Jiangzhuo mixture regulating glucose and lipid metabolism in obese rats.@*METHODS@#Thirty healthy male SD rats were randomly divided into normal control group, model control group, and Jiangzhuo mixture treatment group, with 10 rats in each group. The rats in the normal control group were fed with normal diet, the obesity model was induced by feeding high-fat diet in the model control group and the Jiangzhuo mixture treatment group, the rats in the treatment group were given with Jiangzhuo mixture 50 g/kg by gavage. After 8 weeks of intervention, the blood glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured in the three groups. Quantitative reverse transcription PCR were used to detect the expression levels of PR domain containing 16 (PRDM16) and uncoupling protein 1 (UCP1) in white and brown adipose tissues of the rats in each group; Western blotting was used to detect the expression of PRDM16 in the white and brown adipose tissue of rats, and Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) and inhibitor of NF-κB alpha (IκBα) in the white adipose tissue; immunohistochemistry was used to detect the expression of UCP1 protein in white and brown adipose tissues.@*RESULTS@#Compared with the normal control group, the white fat weight (P<0.01), white fat coefficient (P<0.05) and Lee's coefficient (P<0.01) were significantly increased in the model control group; the contents of GLU, TC, TG and LDL-C were all increased, and the content of TG was significantly increased (P<0.05) in the model control group. The mRNA and protein expression levels of PRDM16 and UCP1 in white fat and brown fat were significantly decreased (P<0.05) in the model control group. Compared with the model control group, the white fat weight and white fat coefficient and Lee's coefficient were significantly reduced in the Jiangzhuo mixture treatment group (all P<0.01), the levels of GLU, TC, TG, and LDL-C in the the treatment group were all reduced, and the content of TG was reduced more obviously (P<0.01); expression levels of PRDM16 and UCP1 mRNA and protein were increased in brown and white adipose tissue. Compared with the normal control group, the expression levels of TLR4, phospho-IκBα and NF-κB-p65 proteins in white adipose tissue of the model control group were significantly increased (all P<0.01), while the expression levels of these proteins in the treatment group were significantly lower than those in the model control group (all P<0.05).@*CONCLUSIONS@#Jiangzhuo mixture can alleviate high-fat diet-induced increase in body fat, abnormal expression of biochemical indexes and promote the expression of key proteins including UCP1 and PRDM16 in white and brown adipose tissues by regulating TLR4/IκBα/NF-κB signaling pathway.
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Rats , Male , Animals , NF-kappa B/metabolism , Rats, Sprague-Dawley , Glucose , Lipid Metabolism , Toll-Like Receptor 4 , Cholesterol, LDL/metabolism , NF-KappaB Inhibitor alpha/metabolism , Medicine, Chinese Traditional , Signal Transduction , Triglycerides , Transcription Factors/metabolism , Obesity , RNA, MessengerABSTRACT
Besides UCP1-dependent thermogenesis pathways, UCP1-independent thermogenesis pathways also could increase heat production in adipose tissue to combat obesity. N-Acyl amino acids (NAAs) have been suggested as novel endogenous uncouplers to induce mitochondria UCP1-independent thermogenesis in adipose tissue. Here, we use mouse skeletal muscle C2C12 cells which lack of UCP1 as UCP1 negative cell models. Comparing with its corresponding common fatty acid—oleate, one of the NAAs—N-Oleoylglycine (NOGly), which is highly expressed in the plasma of HFD mice, is selected to study their effects and mechanisms on mitochondrial thermogenesis. We found that 60 μmol / L oleate could induce mitochondrial oxidative phosphorylation protein levels, as well as increase mitochondria thermogenesis-related genes (COX8b, DIO2, UCP3) expression (P < 0. 05) . However, 60 μmol / L NOGly damaged the production and oxidative phosphorylation of mitochondria, significantly down-regulated expression of thermogenic genes (PGC1a, COX8b, COX2, DIO2, UQCRFS1and UCP3) (P< 0. 01), induced the production of reactive oxygen species (ROS) in the mitochondria, and enhanced the oxidative stress in cells. Our study found that oleate can induce UCP1-independent thermogenesis under 60 μmol / L addition dose, whereas NOGly does not due to the induction of oxidative stress in cells.
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Objective:To observe the expression of brown adipose tissue (BAT), cells, proteins and corresponding genes in Yang deficiency model mice induced by Rhei Radix et Rhizoma suspension, and to explore the thermogenesis of processed products of Aconiti Lateralis Radix Praeparata with Jianchang faction characteristics. Method:Twenty mice, half male and half female, were randomly selected as the normal female and male groups. And the other 80 mice were administrated with Rhei Radix et Rhizoma suspension (the content of 0.25 g·mL-1) to establish Yang deficiency model, after the model was established, they were randomly divided into the model female and male groups, female and male groups of Shengfupian, female and male groups of Yinfupian, female and male groups of Yangfupian, 10 mice in each group. Mice were intragastric administrated with corresponding medical solution for two weeks (1.54 g·kg-1·d-1) according to groups. Normal group and model group were given equal volume distilled water. After administration, BAT of scapular region of mice was collected and the changes of BAT cells were observed by hematoxylin-eosin (HE) staining. The expression of uncoupling protein 1 (UCP1) and its mRNA were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:Compared with the normal group of the same sex, the proportion of BAT in the model group decreased significantly (P<0.01). Compared with the model group of the same sex, the proportion of BAT in female mice from Shengfupian and Yinfupian groups increased significantly (P<0.01), while there was no significant difference between each administration group and model group in the male mice. Compared with normal mice of the same sex, there were many scattered vacuoles in BAT cells of the model group, and fewer cells could be observed due to larger vacuoles. Compared with the model group of the same sex, BAT cells in mice from the Shengfupian group showed fewer vacuoles, smaller cells and tight arrangement, the density of BAT cells in mice from the Yangfupian group also increased significantly, while the vacuoles in BAT cells of mice from the Yinfupian group decreased relatively and the cells did not increase significantly. Compared with the same sex mice, the expression level of UCP1 in the model group and the normal group was statistically significant (P<0.05, P<0.01). In the female mice, the expression level of UCP1 in Yangfupian group was significantly higher than that in the model group (P<0.05), each administration group of male mice was significantly different from that of the model group of the same sex (P<0.05), of which Yangfupian was the most significant. The relative expression of UCP1 mRNA in the model group was significantly lower than that in the normal group of the same sex (P<0.05, P<0.01). In the female mice, compared with the model group, the relative expression levels of UCP1 mRNA in Yangfupian group, Shengfupian group and Yinfupian group increased significantly (P<0.05, P<0.01), compared with Yangfupian group, the relative expression levels of UCP1 mRNA in Shengfupian and Yinfupian were also significantly different (P<0.05). In the male mice, compared with the model group, the relative expression of UCP1 mRNA in Yangfupian group was significantly increased (P<0.01), but there was no significant difference in Shengfupian group and Yinfupian group, in addition, compared with Yangfupian group, the relative expression of UCP1 mRNA in Shengfupian group and Yinfupian group had significant difference (P<0.05). Conclusion:Shengfupian, Yinfupian and Yangfupian all have obvious improvement on Yang deficiency syndrome induced by Rhei Radix et Rhizoma suspension. The mechanism may be to promote the expression of UCP1 protein and its mRNA and enhance the activity of BAT. And the effect of Yangfupian is the best.
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Objective To investigate the expression of peroxisome proliferator-activated receptor γ (PPARγ) and uncoupling protein-1 (UCP-1) after sleeve gastrectomy in Zucker rats and to discuss the weight loss mechanisms.Metbods 30 male Zucker rats aged 10 weeks were randomly divided into 3 groups:the operation group (10 rats),the sham operation group(10 rats) and the diet-pairing group (10 rats).The rats were decapitated to retrieve the retroperitoneal adipose.mRNA and protein expressions of PPARγ and UCP-1 were detected by RT-PCR and Western blot.Results As for the operation group,the weight decreased significantly after the operation compared to the other two groups((250±5.8) g,(370±10.0) g,(310±9.6) g,respectively,P＜0.05).The expressions of PPARγ and UCP-1 gene of mRNA and protein were all significantly higher in the operation group (P＜0.05).Conclusions SG can up-regulate the expressions of thermogenic gene PPARγand UCP-1 in adipose in Zucker rats,browning the white adipose tissue,which was one of the important mechanisms of weight loss.
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Objective@#To determine the change of gene expressions in human perirenal adipose tissue (PAT) and oblique abdomen subcutaneous adipose tissue (SAT) of overweight and obese subjects.@*Methods@#Ninety-seven patients, including 35 overweight/obese patients and 62 non-obese patients, who underwent renal surgery were included. The clinical data and various gene expressions in PAT and SAT of two groups were analyzed.@*Results@#Body mass index, waist circumference, systolic blood pressure, resting heart rate, fasting blood glucose, and serum creatinine were significantly higher in overweight/obese patients than those in non-obese patients(P<0.05 or P<0.01). Compared with non-obese patients, PAT adipocytes showed bigger, and the expressions of uncoupling protein-1 (UCP1) mRNA and protein were markedly lower in overweight/obese patients. The mRNA expressions of CIDEA and adiponectin in PAT of overweight/obese patients were significantly lower, while leptin, monocyte chemotactic protein 1, interleukin (IL)-6, and IL-10 mRNA expressions were significantly higher. There were no significant differences in the related gene expressions of SAT between the two groups.@*Conclusions@#Different parts of adipose tissue reveal various characteristics, and play different roles in the occurrence and development of obesity. UCP1 expression is decreased in PAT of overweight/obese patients, with the changes of adipocytokine expressions. (Chin J Endocrinol Metab, 2018, 34: 567-572)
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This article is the translation of Mast Cells Promote Seasonal White Adipose Beiging in Humans, published in the Diabetes in May, 2017(Diabetes 2017,66:1237-1246), with the consent of Diabetes.This study mainly investigated the mechanism of the beiging of white adipose tissue(WAT).Studies in rodents suggested that cold shock and a number of immune mediators were important for the beiging of subcutaneous white adipose tissue (SC-WAT).This study observed the seasonal beiging of SC-WAT from lean humans, measured the gene expression of various immune cell markers, and performed multivariate analysis of the gene expression data to identify genes that could predict uncoupling protein-1(UCP-1) expression.The mechanism of the induction of UCP-1 from adipocytes by mast cells was also explored by in vitro experiment.The results showed that TIB64 mast cells responded to cold shock by releasing histamine and interleukin 4 (IL-4) which promoted the expression of UCP-1 and the lipolysis of 3T3-L1 adipocytes.Pharmacological block of the degranulation of mast cells potently inhibited the release of histamine and adipocyte UCP-1 mRNA induction by conditioned medium.In summary, mast cells are an important immune cell type in the beiging of WAT which sense colder temperatures, and release factors that promote UCP-1 expression.
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Objective To investigate the effect of ambient temperature on body mass, thermogenic activity and un-coupling protein-1 ( UCP1) content of brown adipose tissue ( BAT) in tree shrews ( Tupaia belangeri) , and to provide the-oretical basis for establishing tree shrews model of obesity.Methods Forty healthy adult tree shrews with similar body mass were uesd in our experiment.The tree shrews were divided into five groups (n=8):control group (0 d), the ani-mals were maintained under 25 ±1℃ and 12L:12D ( light : dark, lights on 08:00) photoperiod; and the animals were maintained under 5 ±1℃and 12L:12D photoperiod for 7 d, 14 d, 21 d and 28 d groups, respectively.At the end of ex-periment, the changes of body mass, nonshivering thermogenesis (NST), BAT mass and uncoupling protein 1 (UCP1) con-tent were determined.Results Compared with the control group (0 d), the body mass, NST, BAT mass and UCP1 con-tent of the cold acclimation groups were improved significantly, the BAT color also obviously deepened, and after cold accli-mation for 28 d, the body mass, NST, BAT mass and UCP1 content were increased by 26.32%, 20.65, 53.85%and 43%, respectively.Apparently, the UCP1 content was significantly positively correlated with BAT mass and NST.Conclusions BAT proliferation may be induced and UCP1 expression upregulated by cold acclimation in Tupaia belangeri, therefore, en-hancing the thermogenic activity of brown adipose tissue to increase energy expenditure.We would speculate that BAT might be used as a target organ for treatment of obesity by energetic approach in the future.
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<p><b>OBJECTIVE</b>To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).</p><p><b>METHODS</b>30 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.</p><p><b>RESULTS</b>Significant 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).</p><p><b>CONCLUSION</b>Our 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.</p>
Subject(s)
Animals , Male , Mice , Adipose Tissue, Brown , Adiposity , Dietary Fats , Pharmacology , Ion Channels , Genetics , Metabolism , Mice, Inbred C57BL , Mitochondrial Proteins , Genetics , Metabolism , RNA, Messenger , Genetics , Metabolism , Triglycerides , Chemistry , Pharmacology , Uncoupling Protein 1 , Weight LossABSTRACT
The effect of pioglitazone on the expression of genes relative to differentiation and function of primary brown adipose tissue cells was detected for the new treatment of obesity and type 2 diabetes.The results showed that pioglitazone promoted the differentiation and function of brown adipocytes( P＜0.05 ).
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Objectives : A diverse range of adverse effects has been linked to the application of antidepressants for the treatment of depressive disorder. Recently, evidence has been emerging of the adverse metabolic effects of antidepressants. This study investigated the effects of antidepressants on plasma glucose and other factors in the fat and muscle tissue relating to metabolism. METHODS : Long-Evans-Tokushima-Ostuka (LETO) rats were used to evaluate the effects of different antidepressants. Amitriptyline, fluoxetine, and mirtazapine were administered to each of three subgroups for 4 weeks, between 11 and 15 weeks old, while a fourth subgroup was administered no antidepressant during the same period. Changes of weight and daily intake were monitored. Tissues and blood were collected at 15 weeks. RESULTS : The fluoxetine subgroup showed lower weight gain and lower food efficacy ratio than did the other subgroups. Blood glucose and other circulating factors showed no significant differences among groups, except for the leptin levels of the fluoxetine subgroup. However, the amitriptyline and mirtazapine subgroups showed similar patterns in the response of mRNA expression of peroxisome proliferator-activated receptors gamma cofactor-1 and uncoupling protein-1, 2, 3. CONCLUSION : These results could indicate possible differences in metabolic response based on the kind of antidepressant used.
Subject(s)
Animals , Rats , Amitriptyline , Antidepressive Agents , Blood Glucose , Depressive Disorder , Energy Metabolism , Fluoxetine , Glucose , Leptin , Mianserin , Muscles , Peroxisome Proliferator-Activated Receptors , Plasma , RNA, Messenger , Weight GainABSTRACT
p38 mitogen-activated protein kinase (p38) is a member of MAP kinase family. Its widespectrum roles in the control of energy metabolism have been indicated in numerous studies. P3 8 participates in the energy metabolism in all major tissues/organs involved in the control of energy metabolism, including adipose tissue, skeletal muscles, islet cells, and liver. In white adipose tissue, p38 plays an important role in adipose differentiation and glucose uptake although it is still inconclusive whether this role of p38 is stimulatory or inhibitory. The stimulatory role of p38 in transcription of the uncoupling protein 1 ( UCP1 ) gene in brown adipose tissue is relatively clear. A fundamental role for p38 in the differentiation of skeletal muscles and mitochondrial biogenesis in skeletal muscles is rather definitive although the role of p3 8 in glucose uptake of skeletal muscles remains controversial. In islet cells, p38 appears to be involved in β-cell apoptosis. P38 has been indicated in the control of preproinsulin gene transcription, but remains controversial. However, it seems clear that p38 does not play a significant role in insulin secretion. In the liver, p38 plays a central role in hepatic glucose and lipid metabolism. Activation of p38 participates in the processes to increase blood glucose levels through reducing glycogen synthesis and increasing hepatic gluconeogenesis. P38 appears to prevent fat storage by inhibiting hepatic lipogenesis and promoting fatty acid oxidation in the liver. Additionally, p38 may play a critical role in cholesterol metabolism by regulating expression of the LDLR gene and bile metabolism. P38 does not only participate in various physiological and pathophysiological processes in cardiomyocytes, but also is heavily involved in the development of atherosclerotic lessions through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells.