Effect of Yinfupian and Yangfupian on Brown Adipose Tissue of Yang Deficiency Mice / 中国实验方剂学杂志

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.

Supplementation of Fermented Barley Extracts with Lactobacillus Plantarum dy-1 Inhibits Obesity via a UCP1-dependent Mechanism / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats.@*METHODS@#In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw).@*RESULTS@#In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity.@*CONCLUSION@#These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.

Expression of peroxisome proliferator-activated receptor γ and uncoupling protein-1 after sleeve gastrectomy in obese diabetic rat / 中华内分泌外科杂志

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.

Electroacupuncture Relieves Obesity by Up-regulating PGC-1 α/UCP-1 Signaling in White Adipose Tissue in Diet-induced Obesity Rats / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the activities of peroxisome proliferator-activated receptor gamma coactivator-1 alpha/uncoupling protein-1 (PGC-1 α/UCP-1) signaling pathway in white adipose tissue(WAT)of diet-induced obesity (DIO) rats, so as to reveal its underlying mechanism in body weight loss. METHODS: Thirty-four male Wistar rats were randomly divided into normal diet (control, n＝10), high fat diet (model), sham EA-acupoint and EA groups (n＝8 in each of the latter 3 groups). The obesity model was established by feeding the rats with high fat diet containing lard oil, sugar, albumen powder, cholesterol, salt and sodium cholate for 12 weeks. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST 36) and "Tianshu" (ST 25) or sham acupoints (about 5 mm beside ST 36 and ST 25) for 30 min, once daily, 5 times per week for a total of 8 weeks. During the treatment, all rats were fed with normal diet, and their body weight and length were measured once a week for calculating the Lee's index. The contents of serum total cholesterol (TC) and triglyceride (TG) were measured by using biochemical methods. The immunoactivity of PGC-1 α and UCP-1 in the abdominal WAT was detected by immunohistochemistry. RESULTS: After modeling, the Lee's index, serum TC and TG contents were significantly increased, and the levels of serum HDL-C, and PGC-1 α and UCP-1 immunoactivity in WAT considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the Lee's index, TC and TG contents were significantly down-regulated while HDL-C and PGC-1 α and UCP-1 immunoactivity were obviously up-regulated in the EA-acupoint group relevant to the model group (P<0.05). CONCLUSION: EA can effectively reduce the body weight and adipose content in obesity rats, which may be closely related to its effect in up-regulating PGC-1 α/UCP-1 signaling in WAT, suggesting an efficacy of EA in promoting the browning of WAT.

Effects of Aerobic and Resistance Exercises on Morphology and Activity of Brown Adipose Tissues in Rats / 中国运动医学杂志

Objective To compare the effect of aerobic and resistance exercise on brown adipose tissues in rats.Methods Sprague-Dawley rats were randomly assigned to a control(C)group,an aerobic exercise (T) group and a resistance exercise(L)group.The rats of group T performed treadmill exercise 5 days per week for 8 weeks,while those of group L climbed vertical ladders with progressively increased weights once in 3 days for 8 weeks.All rats were weighed before and after the intervention.Then the bilateral interscapular brown adipose tissue was isolated and weighed at 48h after the last exercise.The hematoxylin-eosin staining was used to observe the morphology of adipocytes,and the quantitative real-time PCR and Western blotting were employed to detect the mRNA and protein expression of browning genes [PR-domain-containing 16 (PRDM 16),PPAR gamma coactivator-1α (PGC-1 α) and uncoupling protein 1(UCP1)] respectively.Results After the intervention,the increment of weight of group T and group L were only 52％ and 70％ of group C(P＜0.01 and P＜0.05).The weight of BAT in both group T and L was lower than group C,but without significance(P＞0.05).The average size of lipid droplets in group T decreased significantly(P＜0.01) and slightly in group L(P＞0.05) compared with group C.The PRDM16,PGC-1α and UCP1 mRNA expression of group T was 1.78(P＜0.01),2.2(P＜ 0.01) and 1.3(P＞0.05) times of group C,while that of group L was 1.30(P＞0.05),1.25(P＞0.05) and 1.21(P＞0.05) times of group C.The PRDM16,PGC-1α and UCP1 protein level in group T was 1.46-fold(P＜0.05),1.56-fold(P＞0.05)and 1.20-fold(P＞0.05),while that of group L was 1.08-fold(P＞0.05),0.94-fold(P＞0.05) and 1.20-fold(P＞0.05) of group C.Conclusion Eight weeks of aerobic exercise can significantly make the lipid droplets of adipocyte smaller,increase the differentiation and metabolic activity of BAT,and weakly stimulate BAT thermogenesis.However,8 weeks of resistance exercise has no significant effect on BAT.

Effects of Humulus lupulus extract on function of primary brown adipose tissue cells and its mechanisms / 中草药

Objective: To investigate the effects of Humulus lupulus extract on the function of primary brown preadipocyte and its mechanisms, and try to provide new treatment for obesity and type 2 diabetes. Methods: Primary brown adipocytes in newborn rats were cultivated in vitro. After adding different doses of H. lupulus extract, MTT method was used to detect the cell proliferation, and oil red O staining method was used to analyze the lipid droplets consumption rate of H. lupulus extract on the brown adipocyte. The proteins expression of brown adipocytes (such as UCP1, p38αMAPK, and PGC1α) in different groups was detected by Western blotting. Results: The cell proliferation of primary brown preadipocytes was not effected by H. lupulus extract. Compared with control group, with the increasing dose, the lipid droplets consumption rate of H. lupulus extract on the brown adipocyte was increased. The expression of UCP1, p38αMAPK, and PGC1α was upregulated compared with the control group. Conclusion: H. lupulus extract may improve the heat production of brown adipocytes, and strengthen the energy metabolism. The possible mechanism may via enhancing p38MAPK-PGC1α-UCP1 cascade reaction, sequentially increasing the expression of brown fat specificity protein UCP1.

Effects of Acute Exercises of Different Intensities on the FNDC5 and UCP-1 Expression in Epididymal WAT of Rats / 中国运动医学杂志

Objective To investigate the effect of acute exercises of different intensities on the "browning" of epididymal white adipose tissue(WAT) in rats.Methods Thirty Sprague-Dawley male rats were randomly divided into a control group(C,n=6) and an exercises group(E,n=24).Rats in group E were further randomly divided into a moderate intensity exercise (EM,n=12,V=15 m/min) group and a high intensity intermittent exercise(EH,n=12,V=35 m/min,6min's exercises followed by 5 min's rest,repeating 3 times) group.Right after and 6 hours after the acute exercises,the epididymal WAT was taken,and the fibronectin type Ⅲ domain-containing 5 protein(FNDC5) and the uncoupling protein 1(UCP-1) mRNA were detected using RT-qPCR,while the level of FNDC5 and UCP-1 protein was evaluated using Western Blotting.Results Right after the acute exercises,compared with group C,the level of FNDC5 mRNA in group EH increased significantly (P＜0.01),while that of UCP-1 mRNA in group E decreased immediately(P＜0.05) but increased significantly six hours later(P＜0.05).Compared with group C,the level of FNDC5 in groups EM and EH tended to rise,and that of group EM increased significantly(P＜0.05).Compared with group C,the level of UCP-1 in group EM and EH had the tendency to rise,and it increased significantly immediately after exercises in group EH (P＜0.05).Conclusion The acute exercise at different intensities can promote the level of FNDC5 and UCP-1 in epididymal white adipose tissue,"browning" and heat production from fat issues.The level of UCP-1 mRNA increased significantly at 6 hours after exercises,while that of FNDC5 mRNA increased most immediately after the high-intensity intermittent exercises.

Effect of hypobaric hypoxia and cold exposure on formation of brown adipose tissue in mice / 中国比较医学杂志

Objective To investigate the effect of hypobaric hypoxia and cold exposure on brown adipose tissue in mice. Methods Twenty-four 6-week old SPF C57BL/6 male mice were randomly divided into 4 groups with 6 mice in each group: normal atmospheric pressure and temperature group ( 18~22℃, 20~60 m ) ( NTNP ) , low atmospheric pressure and normal temperature group ( 18~22℃, altitude of 5000 m ) ( NTLP ) , normal atmospheric pressure and cold exposure group(0~6℃, altitude of 20 ~60 m)(LTNP), low atmospheric pressure and cold exposure group(0 ~6℃, altitude of 5,000 m)(LTLP). The experimental period was 4 weeks. The body weight was measured at the beginning and end of the experiment. By the end of the four-week trial, the back and inguinal fat were dissected and observed by histology using HE staining. The expression of UCP-1 as the marker of brown adipose tissue in the back fat was detected by qPCR and western blot. Results The body weight gain of NTNP group was higher ( P< 0. 05 ) than the other three groups. Meanwhile, the color of the back and groin fat tissue of mice of LTNP and LTLP groups were darker, the blood supply in mice of these two groups was richer than the NTLP group. The volume of adipose tissue of NTNP group was higher than others. The histology showed that the back adipose cells of the mice were smaller and darker and full of multilocular lipid droplets, exhibiting a typical morphology of brown fat cells. Compared with the NTNP and NTLP groups, the mRNA and protein levels of UCP-1 were higher under cold exposure, while low atmospheric pressure had a tendency to reduce the mRNA expression of UCP-1. Conclusions The formation of brown fat is affected by the imitated conditions of low atmospheric pressure and cold exposure, and is more closely related to the decresed temperature.

Bofutsushosan ameliorates obesity in mice through modulating PGC-1α expression in brown adipose tissues and inhibiting inflammation in white adipose tissues / 中国天然药物

The inducible co-activator PGC-1α plays a crucial role in adaptive thermogenesis and increases energy expenditure in brown adipose tissue (BAT). Meanwhile, chronic inflammation caused by infiltrated-macrophage in the white adipose tissue (WAT) is a target for the treatment of obesity. Bofutsushosan (BF), a traditional Chinese medicine composed of 17 crude drugs, has been widely used to treat obesity in China, Japan, and other Asia countries. However, the mechanism underlying anti-obesity remains to be elucidated. In the present study, we demonstrated that BF oral administration reduced the body weight of obese mice induced by high-fat diet (HFD) and alleviated the level of biochemical markers (P < 0.05), including blood glucose (Glu), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C) and insulin. Our further results also indicated that oral BF administration increased the expression of PGC-1α and UCP1 in BAT. Moreover, BF also reduced the expression of inflammatory cytokines in WAT, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These findings suggested that the mechanism of BF against obesity was at least partially through increasing gene expression of PGC-1α and UCP1 for energy consumption in BAT and inhibiting inflammation in WAT.

Influence of protein phosphatase 5 on the lipid metabolism in mice / 中国比较医学杂志

Objective To investigate the effect of protein phosphatase 5 (PP5) on lipid metabolism in the PP5 knockout (KO) mice.Methods Male PP5 KO and wild type (WT) mice at the age of 6 weeks were used in this study. In order to study the effect of high fat diet ( HFD) feeding, the body weight was measured.The liver histology was examined by HE and oil red O staining.To further verify PP5 functions in the adipogenesis, in vitro experiment was carried out using mouse embryonic fibroblasts (MEF).Western blotting and real-time PCR were performed to quantified the expression of lipid metabolism-related genes in the liver tissues.Results Compared with the WT mice, the body weight gain was slower in the KO mice.The size of the lipid droplets was smaller and the quantity was less in the KO mouse liver tissue.In vitro study revealed that the KO mouse MEF cells showed less differentiated adipocytes with smaller lipid droplets than the WT MEF cells.This observation was further confirmed by detecting the expression of adipogenesis-related genes in the HFD liver.The markers of adipocyte differentiation, such as CD36, AP2, PPARγ2, and Glut4, were significantly decreased, while energy expenditure-related markers, such as phosphorylation of GR and expression of UCP1, were significantly increased.Conclusions Protein phosphatase 5 may play a regulatory role in the mouse lipid metabolism through regulating the de-phosphorylation of p-GR and enhancing the expression of UCP1.

Adaptive thermogenesis of the brown adipose tissue in tree shrews (Tupaia belangeri) during cold acclimation / 中国实验动物学报

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.

Brown adipose tissue: what have we learned since its recent identification in human adults / Tecido adiposo marrom: o que aprendemos desde sua recente identificação em humanos adultos

Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis. Arq Bras Endocrinol Metab. 2014;58(9):889-99.

O tecido adiposo marrom, órgão essencial para a termorregulação de animais hibernantes e pequenos devido à sua capacidade desacopladora, era até poucos anos considerado presente apenas em recém-nascidos na espécie humana. A identificação do tecido adiposo marrom em adultos com o desenvolvimento e uso da tomografia de emissão de pósitron marcado com 18-fluorodesoxiglicose (PET-FDG) gerou questões sobre sua real importância para nosso metabolismo. Nesta revisão, discutiremos o que aprendemos nesse tempo, assim como conceitos antigos e novos, alguns marginalizados por décadas, como a termogênese induzida por dieta. Arq Bras Endocrinol Metab. 2014;58(9):889-99.

Diferentes vías de lipólisis como posibles opciones terapéuticas de la obesidad / Different routes of lipolysis as possible new therapeutic approaches of obesity

Objetivo: la obesidad ha aumentado en todo el mundo, no obstante existen pocas opciones terapéuticas novedosas y la inclinación a actividades cruentas para la terapia de obesidad y diabetes mellitus 2 no dejan de ser un riesgo. Con el fin de valorar el efecto de compuestos sobre la actividad de la célula grasa, estudiamos en forma preclínica la actividad de ácido valproico, tricostatin a (inhibidor de histonas deacetilasas) y EID1 (inhibidor de EP300), el cual reduce la actividad de PPARg en un modelo de células preadipocíticas 3T3-l1. Métodos: se realizó transfecciones transitorias con lipofectamina a las células 3T3-l1 y 293. las células unipotentes 3T3-L1 fueron sometidas a diferenciación con el coctel específico para diferenciación y se les adicionaron los compuestos a concentraciones fisiológicas para las células. Se valoró la expresión de UCP1 mediante Western blot y los experimentos se realizaron por triplicado. Resultados: se observó que el efecto de tricostatin a fue mayor que el del ácido valproico en actividad lipolítica, no obstante ambos compuestos ejercen una efecto aditivo sobre la actividad de EID1 en la diferenciación de la célula adiposa. EID1 es capaz de estimular la actividad de proteína UCP1, cuya expresión es propia del adipocito marrón. Conclusiones: EID1 es una proteína que puede ser referente para inducir una célula adiposa calorigénica más activa, reduciendo la acumulación de lípidos en célula grasa. el efecto de ácido valproico y tricostatin a pueden servir de parámetro para la búsqueda de nuevos planes terapéuticos dirigidos a la obesidad. (Acta Med Colomb 2012; 37: 125-130).

Objective: obesity has increased worldwide, but there are currently few novel therapeutic options and the tendency to invasive procedures for the therapy of obesity and diabetes mellitus 2 are still an important risk. in order to assess the effect of compounds on the fat cell activity, we studied preclinically the activity of valproic acid, tricostatin a (histone deacetylase inhibitor) and EID1 (EP300 inhibitor) which reduces the activity of PPARg, in a model of preadipocyte 3T3-l1 cells. Methods: transient transfections were performed with lipofectamine in 3T3-l1 and 293 cells. Unipotent 3T3-L1 cells underwent differentiation with the specific cocktail and the compounds were added to cells in physiological concentrations. We assessed the UCP1 expression through western blot, and the experiments were performed in triplicate. Results: we observed that the effect of tricostatin a was higher than that of the valproic acid in regard to lipolytic activity; however, both compounds exert an additive effect on EID1 activity in adipose cell differentiation. EID1 is able to stimulate the activity of protein UCP1, whose expression is characteristic of brown adipocyte. Conclusions: EID1 is a reference protein to induce in the adipose cell higher caloric activity, reducing the accumulation of lipids in the adipocyte. The effect of valproic acid and tricostatin a can serve as a parameter for the search of new targeted therapeutic plans for obesity. (Acta Med Colomb2012; 37: 125-130).

The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus / Papel da proteína desacopladora 1 (UCP1) no desenvolvimento da obesidade e do diabetes melito tipo 2

It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

Está bem estabelecido que fatores genéticos têm papel importante no desenvolvimento do diabetes melito tipo 2 (DM2) e obesidade e que indivíduos suscetíveis geneticamente podem desenvolver essas doenças metabólicas após exposição a fatores de risco ambientais. Assim, grandes esforços têm sido feitos para a identificação de genes associados ao DM2 e/ou à obesidade. A proteína desacopladora 1 (UCP1) é principalmente expressa no tecido adiposo marrom e atua na termogênese, regulação do gasto energético e proteção contra o estresse oxidativo, mecanismos associados tanto à patogênese do DM2 como à obesidade. Portanto, UCP1 é um gene candidato para o desenvolvimento dessas doenças. De fato, diversos estudos relataram que os polimorfismos -3826A/G, -1766A/G e -112A/C na região promotora, Ala64Thr no éxon 2 e Met299Leu no éxon 5 do gene UCP1 estão possivelmente associados à obesidade e/ou ao DM2. Entretanto, os resultados são ainda controversos em diferentes populações. Então, o objetivo deste estudo foi revisar o papel da UCP1 no desenvolvimento dessas doenças metabólicas.

The Relationships between UCP-1 Polymorphism and the Degree of Obesity or Plasma Lipid Profile in Prepubertal Children

Uncoupling protein-1 (UCP-1) plays a major role in thermogenesis at brown adipose tissues and has been implicated in the pathogenesis of obesity and metabolic disorders. The purpose of this study was to estimate the effects of A-3826G polymorphism in 117 Korean prepubertal children aged 8-11 years olds. Anthropometry by bioelectrical impedance analysis method, plasma lipid profiles by auto-biochemical analyzer and UCP-1 genotyping by PCR-RFLP were done. The frequencies of UCP-1 genotypes were AA; 17.7%, AG; 57.8%, GG; 26.6%. The frequencies of each G allele (55.5%) was similar to Japanese's (49%) and higher than Caucacian's (25%). No correlation UCP-1 polymorphism and BMI (kg/m2) or the degree of obesity described by the relative percentiles of the standard weight according to height in prepubertal children. However, plasma total- and LDL-cholesterol were significantly increased in G allele when sex, age and weight were adjusted. Our results suggested that G allele of UCP-1 gene was stronger risk factors in hyperLDLcholesterolemia than A allele. This impact might be progressed as the precaution against the revalence of obesity based-metabolic disease.

p38 mitogen-activated protein kinase plays a critical role in the control of energy metabolism and development of cardiovascular diseases / 中南大学学报(医学版)

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.