Effect of obesity, lipids and adipokines on allergic rhinitis risk: a Mendelian randomization study

Abstract Objectives: Observational studies suggested that obesity may promote the development of allergic rhinitis. The aim of this study was to explore the association of obesity, lipids and adipokines with this allergic disease at the genetic level using Mendelian randomization strategies. Methods: Summary data for three obesity indicators (such as body mass index), eight lipid indicators (such as triglycerides) and six adipokines (such as interleukin-6 and adipocyte fatty acid-binding protein) were collected, and suitable instrumental variables were extracted from these summary data according to the three main assumptions of Mendelian randomization. Three Mendelian randomization methods (such as inverse variance weighted) were used to detect the casual effect of the above indicators on allergic rhinitis risk. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Results: After Bonferroni correction, the inverse variance weighted reported that elevated levels of interleukin-6 and adipocyte fatty acid-binding protein were nominally associated with the decreased risk of allergic rhinitis (OR = 0.870, 95% CI 0.765-0.990, p = 0.035; OR = 0.732, 95% CI 0.551-0.973, p = 0.032). The other Mendelian randomization methods supported these results. Obesity, lipids and other adipokines were not related to this allergic disease. Sensitivity analyses found no heterogeneity and horizontal pleiotropy in the study. Conclusion: The study provided some interesting, but not sufficient, evidence to suggest that interleukin-6 and adipocyte fatty acid-binding protein might play a protective role in the development of allergic rhinitis at the genetic level. These findings should be validated by more research. Level of evidence: This was a Mendelian randomized study with a level of evidence second only to clinical randomized trials, and higher than cohort and case-control studies.

Rutin Promotes Browning of 3T3-L1 Preadipocytes and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo investigate the effect of rutin on the browning of 3T3-L1 preadipocytes and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the effect of different concentration of rutin （3.125， 6.25， 12.5， 25， 50， 100， 200 μmol·L-1） on 3T3-L1 cell activity， and Western blot to examine the effect of rutin （12.5， 25， 50 μmol·L-1） on the expression of thermogenesis-associated proteins uncoupling protein 1 （UCP1）， PR domain containing 16 （PRDM16） and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in adipocytes. After the optimal concentration of rutin was determined， the effect of rutin on lipid droplet formation in adipocytes was observed based on oil red O staining， and the expression of nuclear respiratory factor 1 （NRF1）， nuclear respiratory factor 2 （NRF2） and mitochondrial transcription factor A （TFAM）， which were the landmark proteins of mitochondrial biosynthesis， was detected by Western blot. ResultCompared with the blank group， 200 μmol·L-1 rutin inhibited 3T3-L1 cell activity （P<0.01）. Compared with the blank group， at the concentration of 12.5， 25， 50 μmol·L-1 rutin significantly promoted the expression of thermogenesis-associated proteins （UCP1， PRDM16， and PGC-1α） （P<0.01）， which was determined as the optimal concentration. Compared with the blank group， 50 μmol·L-1 rutin significantly increased the immunofluorescence intensity of mitochondrial UCP1 protein in 3T3-L1 cells （P<0.01） and the expression of the markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM） （P<0.01）. In addition， 50 μmol·L-1 rutin significantly inhibited lipid droplet formation of 3T3-L1 adipocytes （P<0.01）. ConclusionRutin inhibited lipid droplet deposition in 3T3-L1 adipocytes and increased the expression of thermogenesis-related proteins （UCP1， PRDM16， and PGC-1α） and markers of mitochondrial biosynthesis （NRF1， NRF2， and TFAM）， thereby inducing the browning of 3T3-L1 adipocytes. This lays a basis for the development of drugs that safely regulate the browning of white cells.

Overexpression of chicken Klf2 promotes klf7 transcription and inhibits adipocyte differentiation / 生物工程学报

Overexpression of Krüppel like factor 2 (Klf2) or Klf7 inhibits adipocyte formation. However, it remains unclear whether Klf2 regulates klf7 expression in adipose tissue. In this study, oil red O staining and Western blotting were employed to study the effect of Klf2 overexpression on the differentiation of chicken preadipocytes. The results showed that Klf2 overexpression inhibited the differentiation of chicken preadipocytes induced by oleate and the expression of pparγ, while promoted klf7 expression in chicken preadipocytes. Spearman correlation analysis was used to study the correlation between the expression data of klf2 and klf7 in the adipose tissue of both human and chicken. The results showed that there was a significantly positive correlation between the expression of klf2 and klf7 in adipose tissues (r > 0.1). Luciferase reporter assay showed that overexpression of Klf2 significantly promoted the activity of chicken klf7 promoter (-241/-91, -521/-91, -1 845/-91, -2 286/-91, -1 215/-91; P < 0.05). In addition, the activity of klf7 promoter (-241/-91) reporter in chicken preadipocytes was significantly positively correlated with the amount of klf2 overexpression plasmid transfected (Tau=0.917 66, P=1.074×10-7). Moreover, Klf2 overexpression significantly promoted the mRNA expression of klf7 in chicken preadipocytes (P < 0.05). In conclusion, upregulation of klf7 expression might be one of the pathways that Klf2 inhibits chicken adipocyte differentiation, and the sequence from -241 bp to -91 bp upstream chicken klf7 translation start site might mediate the regulation of Klf2 on klf7 transcription.

Cellular senescence and type 2 diabetes / 中华内分泌代谢杂志

Cellular senescence is a state in which cells enter permanent cell cycle arrest, which is characterized by senescence-associated secretory phenotype secretion, macromolecular damage, metabolic dysregulation and so on. Recent studies have shown a close relationship between cellular senescence and type 2 diabetes. On the one hand, the glycolipotoxic microenvironment of type 2 diabetes can accelerate cell senescence and accumulation. On the other hand, cellular senescence can promote the development of type 2 diabetes. For example, senescence of pancreatic β-cells leads to β-cell dysfunction and adipocytes senescence results in the secretion of pro-inflammatory cytokines, causing disturbances in lipid metabolism and exacerbating insulin resistance. Moreover, senescence of endothelial cells, retinal endothelial cells, and other cell types contributes to the occurrence of chronic complications in diabetes. Cellular senescence is not only an important factor in the onset of type 2 diabetes but also a consequence of its progression. Targeting cellular senescence holds promise as a new strategy for the treatment of type 2 diabetes.

El tejido adiposo, ¿solo un almacén de energía? / Adipose Tissue, Just an Energy Storage?

Resumen Cuando los alimentos cubren los requerimientos energéticos, el organismo almacena el exceso de calorías como glucógeno en el hígado y el músculo, y los triacilgliceroles en el tejido adiposo. Morfológica y funcionalmente se clasifica en blanco y pardo. El pardo tiene gran cantidad de mitocondrias, almacena los triacilgliceroles en vacuolas y disipa la energía en forma de calor; el blanco almacena energía en gotas lipídicas que ocupan la mayor parte de su volumen. Después de la ingesta de alimentos se libera insulina, lo que hace que externen GLUT4 para absorber glucosa. Los quilomicrones o las lipoproteínas de muy baja densidad (VLDL) transportan los triacilgliceroles a los depósitos de tejido adiposo. Durante el ayuno, por acción del glucagón, se liberan enzimas que degradarán a los tri, di y monogliceroles para liberar a los ácidos grasos. El tejido adiposo libera citocinas pro y antiinflamatorias, así como leptina, adiponectina que regulan el apetito y la saciedad. La proteína cinasa activada por AMP se activa como respuesta a una baja en la cantidad de energía de la célula y le ayuda a mantener un balance energético. En el adipocito promueve la degradación de los triacilgliceroles para liberar a los ácidos grasos que se emplearán como fuente energética. Se requiere de mayor cantidad de estudios para conocer más sobre la función del tejido adiposo como regulador del metabolismo y no solo como almacén de energía.

Abstract When food meets energy requirements, the body stores in the liver and in the muscle the excess of calories as glycogen and triacylglycerols in the adipose tissue. Morphologically and functionally, it is classified into white and brown tissues. Brown tissue has many large mitochondria and stores triacylglycerols in vacuoles and dissipates energy as heat; white tissue stores energy as lipid droplets that occupy most of the adipocyte's volume. After food intake insulin is released, which causes GLUT4 externalization into the cellular membrane to absorb glucose. Chylomicrons or VLDL transport triacylglycerols to adipose tissue depots. During fasting, by the action of glucagon, enzymes are released that will degrade tri-, di- and mono-glycerols to release fatty acids. Adipose tissue releases pro and anti-inflammatory cytokines, as well as leptin and adiponectin that regulate appetite and satiety. AMPK is activated in response to a decrease in the cell's energy and helps it to maintain its energetic balance. In the adipocyte, it promotes the degradation of triacylglycerols releasing fatty acids to be used as an energy source. More studies are needed to learn more about the function of adipose tissue as a regulator of the metabolism and not only as an energy storage.

Correlation of serum FABP4 and PPAR γ levels with nonalcoholic fatty liver disease and type 2 diabetes mellitus / 中华内分泌外科杂志

Objective:To explore the correlation between serum adipocyte fatty acid binding protein 4 (FABP4) and peroxisome proliferator activated receptor gamma (PPAR gamma) levels and metabolism related fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) .Methods:230 patients with T2DM and MAFLD in Zhangjiakou First Hospital from Feb. 2019 to Feb. 2021 were selected. According to their disease conditions, 80 patients with T2DM and without MAFLD were set as simple T2DM group, 78 patients with MAFLD and normal glucose tolerance were set as simple MAFLD group, 72 patients with T2DM and MAFLD were set as T2DM and MAFLD group, and 100 healthy volunteers in the same period were selected as the control group.Results:The levels of HOMA-IR and FABP4 in T2DM patients were significantly higher than those in the control group ( P<0.05) , while the levels of HDL-C, crea and PPAR γ in T2DM grou were significantly lower than those in the control group ( P<0.05) . The levels of BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 in MAFLD group were significantly higher than those in control group ( P<0.05) , while the level of PPAR γ in MAFLD group was significantly lower than that in control group ( P<0.05) . BMI, AST, alt, GGT, TG, HOMA-IR and FABP4 of T2DM patients with MAFLD were significantly higher than those of T2DM patients without MAFLD and control group ( P<0.05) , while HDL-C and PPAR γ were significantly lower than those of T2DM patients without MAFLD and control group ( P<0.05) . HOMA-IR and FABP4 in T2DM patients with MAFLD were significantly higher than those in MAFLD group ( P<0.05) , while HDL-C, crea and PPAR γ were significantly lower than those in MAFLD group ( P<0.05) . FABP4 was positively correlated with HOMA-IR and CREA (all P<0.05) , and negatively correlated with HDL-Cand PPAR γ (all P<0.05) . PPAR γ was positively correlated with TG and ALT (all P<0.05) , and negatively correlated with HOMA-IR ( P<0.05) . Alt, TG, HOMA-IR, FABP4 and PPAR γ were independent risk factors for MAFLD in T2DM patients ( P<0.05) . Conclusion:FABP4 is positively correlated with the occurrence of T2DM and MAFLD, PPAR γ is negatively correlated with the occurrence of T2DM and MAFLD, the negative feedback loop regulation of FABP4 and PPAR γ can cause the occurrence of insulin resistance, so as to improve the risk of T2DM combined with MAFLD, and provide clinical basis for clinical disease prevention and treatment.

Simple obesity of stomach heat and damp obstruction treated with acupoint thread embedding therapy: a randomized controlled trial / 中国针灸

OBJECTIVE@#To explore the therapeutic effect and safety of acupoint thread embedding therapy in treatment of simple obesity of stomach heat and damp obstruction.@*METHODS@#A total of 144 patients with simple obesity of stomach heat and damp obstruction were randomized into an acupoint thread embedding group (72 cases, 3 cases dropped off and 1 case removed) and a sham-embedding group (72 cases, 6 cases dropped off and 3 cases removed). On the base of the lifestyle adjustment, the acupoint thread embedding therapy with PGLA thread was applied to Tianshu (ST 25), Zhongwan (CV 12), Ganshu (BL 18), Shuidao (ST 28), etc. in the acupoint thread embedding group, while in the sham-embedding group, the acupoint selection and operation were all same as the acupoint thread embedding group, but without PGLA thread embedded. In either group, the treatment was given once every 2 weeks, consecutively for 12 weeks and the follow-up was conducted for 3 months after treatment. Separately, before and after treatment as well as in follow-up, the obesity indices (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR] and fat percentage [F%]) were observed in the two groups. Before and after treatment, the indices of blood glucose and insulin (fasting blood glucose [FBG], fasting insulin [FINS] and insulin resistance index [HOMA-IR]), adipocyte factor indices (adiponectin, leptin [LP] and serine protease inhibitor [Vaspin]) and inflammatory factor indices (tumor nercosis factor [TNF-α], interleukin-1β [IL-1β] and interleukin-6 [IL-6]) were observed separately in the two groups. The therapeutic effect and safety were compared between the two groups.@*RESULTS@#After treatment and in follow-up, except WC and WHR in the sham-embedding group, BMI, WC, WHR and F% were all reduced as compared with those before treatment in the two groups (P<0.01, P<0.05), and the values in the acupoint thread embedding group were lower than the sham-embedding group (P<0.01). After treatment, except FBG, LP and Vaspin in the sham-embedding group, FBG, FINS, HOMA-IR, LP and Vaspin were all reduced as compared with those before treatment in the two groups (P<0.01, P<0.05), and adiponectin was increased as compared with that before treatment (P<0.01, P<0.05); the improvements in the acupoint thread embedding group were more significant than the sham-embedding group (P<0.01). After treatment, the levels of serum TNF-α, IL-1β and IL-6 in the acupoint thread embedding group were reduced as compared with the values before treatment and those in the sham-embedding group separately (P<0.01). The total effective rate was 89.7% (61/68) in the acupoint thread embedding group, higher than 19.0% (12/63) in the sham-embedding group (P<0.01). There was no severe adverse reaction reported in the two groups.@*CONCLUSION@#Acupoint thread embedding therapy with PGLA thread can alleviate obesity, regulate glucose metabolism and adipocyte factors activity, improve insulin resistance and inhibit the expression of pro-inflammatory factors in the patients with simple obesity with stomach heat and damp obstruction, and this therapy presents a satisfactory safety in treatment.

Processing and identification of delicate fat particles for clinical application / 中华医学美学美容杂志

Objective:In the process of fat grafting, there is no good solution to achieve delicate filling while retaining the viability of fat particle. There was still no research on the composition and activity of delicate fat particle. In this study, two different methods for delicate fat process were established to explore the feasibility and clinical efficacy.Methods:From December 2015 to June 2016, 5 patients (22-31 years old, with average 26.2 years) with abdominal liposuction in Shanghai Ninth People's Hospital were inclueded. The fat particles were obtained by floating method and filtration method respectively, and compared with emulsified fat/nanofat and traditional fat grafts. The cell viability and composition of adipose tissue were compared in each group through cell viability test, flow analysis and tissue staining.Results:The fat particles obtained by floating and filtration methods, emulsified fat could pass through OT needle. Cell viability test revealed the presence of living cells in the fat obtained by both methods, but not in the emulsified fat. Flow analysis showed that the expression of CD90 in floating group was higher than that in control group ( P=0.048). Conclusions:The delicate fat particle can be obtained by floating or filtration method, which can preserves the tissue integrity and cell viability; meanwhile it can achieve fine needle injection and clinical application.

Equisetin is an anti-obesity candidate through targeting 11β-HSD1

Obesity is increasingly prevalent globally, searching for therapeutic agents acting on adipose tissue is of great importance. Equisetin (EQST), a meroterpenoid isolated from a marine sponge-derived fungus, has been reported to display antibacterial and antiviral activities. Here, we revealed that EQST displayed anti-obesity effects acting on adipose tissue through inhibiting adipogenesis in vitro and attenuating HFD-induced obesity in mice, doing so without affecting food intake, blood pressure or heart rate. We demonstrated that EQST inhibited the enzyme activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a therapeutic target of obesity in adipose tissue. Anti-obesity properties of EQST were all offset by applying excessive 11β-HSD1's substrates and 11β-HSD1 inhibition through knockdown in vitro or 11β-HSD1 knockout in vivo. In the 11β-HSD1 bypass model constructed by adding excess 11β-HSD1 products, EQST's anti-obesity effects disappeared. Furthermore, EQST directly bond to 11β-HSD1 protein and presented remarkable better intensity on 11β-HSD1 inhibition and better efficacy on anti-obesity than known 11β-HSD1 inhibitor. Therefore, EQST can be developed into anti-obesity candidate compound, and this study may provide more clues for developing higher effective 11β-HSD1 inhibitors.

NF-κB regulates brown adipocyte function through suppression of ANT2

The transcription factor nuclear factor of kappa-light-chain-enhancer of activated B cells (NF-κB) is expressed in brown adipocytes, but its role remains largely unknown in the cells. This issue was addressed in current study by examining NF-κB in brown adipocytes in vitro and in vivo. NF-κB activity was increased by differentiation of brown adipocytes through elevation of p65 (RelA) expression. The transcriptional activity of NF-κB was induced by the cold stimulation with an elevation in S276 phosphorylation of p65 protein. Inactivation of NF-κB in brown adipocytes made the knockout mice [uncoupling protein 1 (Ucp1)-CreER-p65f/f, U-p65-KO] intolerant to the cold environment. The brown adipocytes exhibited an increase in apoptosis, a decrease in cristae density and uncoupling activity in the interscapular brown adipose tissue (iBAT) of p65-KO mice. The alterations became severer after cold exposure of the KO mice. The brown adipocytes of mice with NF-κB activation (p65 overexpression, p65-OE) exhibited a set of opposite alterations with a reduction in apoptosis, an increase in cristae density and uncoupling activity. In mechanism, NF-κB inhibited expression of the adenine nucleotide translocase 2 (ANT2) in the control of apoptosis. Data suggest that NF-κB activity is increased in brown adipocytes by differentiation and cold stimulation to protect the cells from apoptosis through down-regulation of ANT2 expression.

Effects of oleic (18: 1n-9) and palmitic (16: 0) fatty acids on the metabolic state of adipocytes / Efectos de los ácidos grasos oleico (18: 1n-9) y palmítico (16: 0) en el estado metabólico del adipocito

Abstract Background: Elevated serum-free fatty acid (FFA) levels induce insulin resistance (IR) or a protective mechanism to IR development in humans; it depends on FFA type. Objetive: This study explores the effects of oleic (OLA - unsatured) and palmitic (PAM - saturated) fatty acids on insulin action in mature adipocytes effect. Methods: Cells were incubated 18 h with or without OLA and PAM at 250 μM, and 500 μM. After the culture period, were measured: adipocyte viability, size, fatty acids mobilisation, insulin signalling proteins, and glucose uptake. Results: Adipocytes exhibited optimal viability tolerances regardless of the kinds of fatty acids used for treatment. However, adipocytes were hypertrophic after OLA and PAM stimuli. Additionally, lipogenesis (lipid synthesis), and lipolysis (lipid breakdown) were significantly increased by treatment with OLA, or PAM (500 μM) compared to control. Moreover, OLA results showed that there was no significant reduction in signalling cascades, except for a downstream proinflammatory response. Instead, PAM hypertrophic adipocytes were insulin resistant with alteration of proinflammatory and stress markers. Conclusions: Current findings suggest that PAM induces insulin resistance, mitochondrial and reticulum stress on fat cells compared to those treated with OLA that, protects adipocytes to all those alterations.

Resumen Introducción: Los niveles elevados de ácidos grasos libres (AGL) en suero inducen resistencia a insulina (RI) o un mecanismo de protección del desarrollo de RI en humanos, esto depende del tipo de AGL. Objetivo: Este estudio explora los efectos de los ácidos grasos oleico (insaturados - OLA) y palmítico (saturados - PAM) sobre la insulina en adipocitos maduros. Métodos: Las células se incubaron 18 h con o sin OLA y PAM a 250 μM y 500 μM. Después del período de cultivo, se evaluó en adipocitos: viabilidad, tamaño, movilización de ácidos grasos, proteínas de señalización de insulina y absorción de glucosa. Resultados: Los adipocitos mostraron viabilidad óptima independientemente de los tipos de ácidos grasos utilizados en el tratamiento. Los adipocitos eran hipertróficos tras estimulo con OLA y PAM. La lipogénesis (síntesis de lípidos) y la lipólisis (degradación de lípidos) aumentaron significativamente con el tratamiento con OLA o PAM (500 μM) en comparación con el control. En los resultados de OLA no se evidenció una reducción significativa en las cascadas de señalización de insulina, a excepción de una respuesta proinflamatoria posterior. En cambio, los adipocitos hipertróficos tratados con PAM presentaron resistencia a la insulina y alteración de los marcadores proinflamatorios y de estrés. Conclusiones: Nuestros hallazgos sugieren que PAM induce resistencia a la insulina, estrés mitocondrial y del retículo en las células grasas en comparación con aquellos tratados con OLA, AGL que, en cambio, protegen a los adipocitos de todas esas alteraciones.

Effects of 2,2',4,4' -tetrabromodiphenyl ether on differentiation of mouse 3T3-L1 cells / 预防医学

Objective@#To investigate the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether ( BDE-47 ) on the differentiation of mouse embryonic fibroblasts-3T3-L1, so as to provide the basis for revealing the mechanism of environmental obesity factors. @*Methods@#The 3T3-L1 cells were divided into five BDE-47 intervention groups ( 25, 18.75, 12.5, 7.5 and 2.5 µmol/L ), a positive control group (1 µmol/L 2, 4-thiazolidinedione) and a negative control group ( 0.1% dimethyl sulfoxide ) for the induction of differentiation. The lipid droplet accumulation in adipocytes was observed by oil red O staining treatment and detection of optical desity ( OD ) on the eighth day of differentiation. Triglyceride ( TG ) content was measured using the histiocyte TG enzymatic assay kit. The mRNA expression of adiponectin and peroxisome proliferator activated receptor-γ ( PPARγ ) was measured by RT-PCR.@*Results@#The positive areas of oil red O staining, OD values, TG content and mRNA expression of adiponectin and PPARγ in 3T3-L1 cells were significantly different among seven groups ( P<0.05 ). The positive areas of oil red O staining and OD values in the BDE-47 groups with different concentrations were higher than those in the negative control group ( P<0.05 ). The 18.75 µmol/L BDE-47 group had higher TG levels than the negative control group ( P<0.05 ). The mRNA expression of PPARγ in the 25, 18.75, 12.5, and 7.5 µmol/L BDE-47 groups and the positive control group was higher than that in the negative control group ( P<0.05 ). The mRNA expression of PPARγ in the 12.5 µmol/L BDE-47 group was higher than that in the 25, 18.75, 7.5, 2.5 µmol/L BDE-47 group and the positive control group ( P<0.05 ). The mRNA expression of adiponectin in the 12.5, 7.5 µmol/L BDE-47 group and the positive control group was higher than that in the negative control group ( P<0.05 ). The mRNA expression of adiponectin in the 12.5 µmol/L BDE-47 group was higher than that in the 25, 18.75, 2.5 µmol/L BDE-47 group ( P<0.05 ). The mRNA expression of PPARγ and adiponectin in the different concentration groups of BDE-47 distributed like inverted "U" shape.@*Conclusion@#BDE-47 can promote the differentiation of 3T3-L1 preadipocytes. Low concentration of BDE-47 may induce adipocyte differentiation by activating PPARγ.

Clinical Efficacy of Modified Xiaoji Baozhong Granules Combined with Scraping in Treatment of Abdominal Obesity with Gastric Heat and Dampnes / 中国实验方剂学杂志

Objective:To evaluate the efficacy of modified Xiaoji Baozhong granules combined with scraping in the treatment of abdominal obesity with gastric heat and dampness syndrome and its effect on adipocytokines. Method:One hundred and forty-four patients were randomly divided into the control group and the observation group， 72 cases in each group. The lifestyle adjustments were conducted in both groups. The observation group was given a comprehensive traditional Chinese medicine regimen of modified Xiaoji Baozhong granules combined with scraping. The control group was given modified Xiaoji Baozhong granules combined with scraping. The course of treatment was three months. The body mass index （BMI）， body fat percentage （FP）， waist circumference （WC）， waist to hip ratio （WHR）， obesity and abdominal fat thickness of the two groups were compared before and after treatment. The levels of fasting blood glucose （FBG）， insulin resistance index （HOMA-IR）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， triglyceride （TG）， total cholesterol （TC）， adiponectin， leptin， resistin， endolipid and tumor necrosis factor-α （TNF-α） were compared between the two groups before and after treatment. The clinical efficacy and safety were evaluated. Result:After treatment， the BMI， FP， obesity， WC and WHR of the observation group were lower than those of the control group （<italic>P</italic><0.01）. After treatment， the abdominal wall fat thickness and intra-abdominal fat thickness of patients in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The FBG， HOMA-IR， TG， TC and LDL of the observation group were lower than those of the control group （<italic>P</italic><0.01）， while the HDL level was higher than the control group （<italic>P</italic><0.01）. Adiponectin in the observation group was higher than the control group after treatment （<italic>P</italic><0.01）. The leptin， resistin， visfatin and TNF-α were lower than those in the control group （<italic>P</italic><0.01）. The total clinical efficacy rate of patients in the observation group was 88.24% （60/68）， which was better than 73.53% （50/68） in the control group （<italic>χ</italic>²=4.755， <italic>P</italic><0.05）. Conclusion:In addition to lifestyle adjustments， modified Xiaoji Baozhong granules combined with scraping treatment can reduce the degree of obesity and fat thickness in patients with abdominal obesity， and regulate lipid， carbohydrate metabolism and adipocytokines， with a better clinical efficacy than simple scraping therapy and the safety in practice.

Regulatory Effect of Modified Banxia Xiexintang on Insulin Resistance of Patients with Nonalcoholic Fatty Liver / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of modified Banxia Xiexintang on nonalcoholic fatty liver （NAFLD） and the regulatory effect on insulin resistance （IR）. Method:One hundred and forty patients were randomly divided into control group and observation group. A total of 63 patients in control group completed the therapy （4 patients fell off or were lost to follow-up， 3 were eliminated）， while 65 patients in observation group completed the therapy （5 patients fell off or were lost to follow-up， none was eliminated）. Both groups' patients got lifestyle intervention， liver protection and lipid regulation. Patients in control group got Huazhi Rougan granule， 1 pack/time， 3 times/day. Patients in observation group got modified Banxia Xiexintang， 1 dose/day. And the course of treatment for the two groups was 12 weeks， and a 12 week follow-up was recorded. Before and after treatment and during the follow-up， fat content of liver was recorded by instantaneous elastic recorder， fasting blood glucose （FBG） and fasting insulin （FINS） were detected， and insulin sensitivity index （ISI）， insulin resistance index （HOMA-IR） and islet <italic>β</italic> cell function index （HOMA-<italic>β</italic>） were detected. After treatment， B-mode ultrasonography and ratio of liver/spleen CT were detected. And levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， adiponectin， leptin， serine protease inhibitor （Vaspin）， tumor necrosis factor （TNF）-<italic>α</italic> and interleukin-6 （IL-6） were detected. And the safety was evaluated. Result:CAP and HOMA-IR in observation group were lower than those in control group after treatment and during the follow-up （<italic>P</italic><0.01）， and ISI and HOMA-<italic>β</italic> were higher than those in control group （<italic>P</italic><0.01）. Amelioration of indexes of blood lipid was better than those in control group （<italic>P</italic><0.01）. Levels of ALT， AST， FBG and FINS were lower than those in control group （<italic>P</italic><0.01）. Scores of traditional Chinese medicine （TCM） syndromes were lower than those in control group （<italic>P</italic><0.01）， ratio of liver/spleen CT and adiponectin was higher than that in control group （<italic>P</italic><0.01）. Levels of TNF-<italic>α</italic>， IL-6， vaspin and leptin were lower than those in control group （<italic>P</italic><0.01）. B-ultrasound efficacy and fat content of liver were superior to those of control group （<italic>P</italic><0.05）. There were no serious adverse events and drug-related adverse reactions. Conclusion:Modified Banxia Xiexintang can regulate glucose and lipid metabolism， improve insulin sensitivity and HOMA-<italic>β</italic> cell function， improve IR， regulate adipocytokines and inflammatory factors， relieve clinical symptoms and liver fat content， and improve CT ratio of liver/spleen， with a better clinical efficacy and safety.

Regulatory Effect of Modified Erzhu Erchentang on Patients with Polycystic Ovary Syndrome and Spleen Deficiency and Phlegm Dampness / 中国实验方剂学杂志

Objective:To observe the regulatory effect of modified Erzhu Erchentang on metabolization of polycystic ovary syndrome （PCOS） with spleen deficiency and phlegm dampness syndrome. Method:Patients 140 cases were divided into control group and observation group. Both groups were given metformin hydrochloride tablets， 500 mg/time， 3 times/day. Control group was given Yuejun Erchen pills， 0.5 g/time， 3 times/day， while observation group was given modified Erzhu Erchentang， 1 dose/day. The course of treatment lasted for 24 weeks. Before and after treatment， levels of fasting blood glucose （FBG）， fasting insulin （FINS）， glycosylated hemoglobin Alc （HbA1c）， 2-hour postprandial blood glucose （2 h PG）， blood lipid， waist circumference （WC）， body mass index （BMI）， waist hip ratio （WHR）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E₂）， dehydroepiandrosterone sulfate （DHEAS）， sex hormone binding globulin （SHBG）， leptin （LP）， adiponectin （APN）， resistin， visfatin and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） were detected. Homeostasis model assessment insulin resistance （HOMA-IR） was calculated， modified Erzhu Erchentang was scored， and recovery of menstruation and ovulation and ovarian volume were recorded. Result:Levels of FBG， 2 h PG， HbA1c， FINS， HOMA-IR， triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， LH， FSH， T， E₂， DHEAS， LP， resistin， visfatin and TNF-<italic>α</italic> in observation group were lower than those in control group （<italic>P</italic><0.01）， and levels of BMI， WC and WHR were lower than those of control group （<italic>P</italic><0.05）. And levels of high-density lipoprotein cholesterol （HDL-C）， SHBG and APN were higher than those in control group （<italic>P</italic><0.01）. Score of modified Erzhu Erchentang was lower than that in control group （<italic>P</italic><0.01）， and ovarian volume was smaller than that in control group （<italic>P</italic><0.01）. The normal rate of BMI was 49.23% （32/65）， which was higher than 30.30% （20/66） in control group （<italic>χ</italic>²=5.151， <italic>P</italic><0.05）. The normal rate of blood lipid was 93.85% （61/65）， which was higher than 81.82 % （54/66） in control group （<italic>χ</italic>²=4.418， <italic>P</italic><0.05）. The normal rate of blood glucose was 96.92% （63/65）， which was higher than 86.36% （57/66） in control group （<italic>χ</italic>²=4.474， <italic>P</italic><0.05）. Conclusion:In addition to adipocytokines， modified Erzhu Erchentang could regulate adipokines of patients of PCOS with spleen deficiency and phlegm dampness， improve glucose， lipid metabolism and overweight， adjust endocrine hormone， reduce clinical symptoms and improve ovarian structure， so as to create conditions for conception.

Clinical Efficacy of Modified Xiao Chengqitang Combined with Acupoint Catgut Implantation in Treating Diet-induced Obesity Syndrome of Stomach Heat Dampness Obstruction / 中国实验方剂学杂志

Objective:To observe the clinical efficacy and safety of modified Xiao Chengqitang combined with acupoint catgut implantation in treating diet-induced obesity （DIO） syndrome of stomach heat dampness obstruction. Method:One hundred and seventy-two patients were randomly divided into control group（84 cases） and observation group（88 cases）. Both groups of patients received diet and exercise lifestyle adjustments， and acupoint catgut implantation was performed， 10 days for 1 time， 5 days intervals and then catgut implantation again， for a total of 6 times. Patients in observation group took modified Xiao Chengqitang granular powder， 10 g/time， with lukewarm boiled water in morning and evening. Patients in control group took modified Xiao Chengqitang granular powder simulant， 10 g/time， with lukewarm boiled water， 2 times/day. The treatment courses continued 4 months in two groups. Then the body mass index （BMI）， fat percentage （F%）， obesity， waist to hip ratio （WHR） were measured before and after treatment. Color Doppler ultrasonography was used to measure abdominal fat thickness， prehepatic fat thickness （AHF）， perirenal fat thickness （PRF）， and visceral fat index （UVI）. Fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein-cholesterol （HDL-C）， low-density lipoprotein-cholesterol （LDL-C）， fasting insulin （FINS）， leptin （LP）， and adiponectin （APN） were detected before and after treatment， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. In addition， safety evaluation was also conducted. Result:The BMI， F%， obesity degree and WHR in observation group were all lower than those in control group （<italic>P</italic><0.05 or <italic>P</italic><0.01）. Subcutaneous fat thickness， AHF， PRF and UVI in observation group were lower than those in control group （<italic>P</italic><0.01）. The TG， TC， LDL-C and FINS levels in observation group were lower than those in control group （<italic>P</italic><0.01）. The LP and HOMA-IR were also lower than those in control group （<italic>P</italic><0.01）， while the APN was higher than that in control group （<italic>P</italic><0.01）. The total effective rate in clinical application was （71/80） 88.75% in the observation group， higher than （57/75） 76.00% in the control group （<italic>χ</italic>²=4.374，<italic> P</italic><0.05）. Conclusion:Modified Xiao Chengqitang combined with acupoint catgut implantation in treating DIO syndrome of stomach heat dampness obstruction can adjust LP， APN and other factors， improve energy metabolism such as sugar and fat， and effectively control obesity with high safety， so it is worthy of clinical use.

VEGF-B antibody and interleukin-22 fusion protein ameliorates diabetic nephropathy through inhibiting lipid accumulation and inflammatory responses

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

Papel de la célula grasa en el riesgo cardiovascular / Role of the fat cell in cardiovascular risk

Resumen La obesidad es una enfermedad crónica, no transmisible, que recientemente ha tenido una connotación especial debido al aumento de su prevalencia en países en vía de desarrollo. Este incremento está relacionado con un aumento en la aparición de enfermedades metabólicas y el riesgo cardiovascular. Si bien la prevalencia de obesidad está aumentando en todos los países del mundo, existen diferencias regionales tanto en la prevalencia como en las tendencias de la obesidad. Por consiguiente, comprender los impulsores de estas diferencias regionales podría ayudar a proporcionar orientación para las estrategias de intervención más prometedoras. A pesar de considerarse una eventualidad simple en una proporción de lo que se ingiere y lo que se gasta, existen muchos factores que regulan esta enfermedad. No es sencillo encontrar medidas terapéuticas para la obesidad, pues sus causas son múltiples. En forma reciente, ha despertado un especial interés la caracterización funcional de los adipocitos, específicamente de los adipocitos beige, dado que su función está íntimamente relacionada con las circunstancias externas del ambiente y tienen una flexibilidad que les permite producir energía y mejorar muchos de los parámetros metabólicos en los individuos. En este manuscrito se hará énfasis en las características de las células adiposas y su influencia en el riesgo cardiovascular.

Abstract Obesity is a chronic non-transmissible disease that has recently had a special connotation due to the increase of its prevalence in developing countries. The increase in obesity is related to an expansion in the appearance of metabolic diseases and cardiovascular risk. Although the prevalence of obesity is increasing in all countries of the world, there are regional differences in both the prevalence and trends of obesity. Therefore, understanding the circumstances of these regional differences could help provide guidance for the most promising intervention strategies. Despite being considered a simple outcome in a proportion of what is ingested and what is spent, there are many factors that regulate this disease. It is not easy to find therapeutic measures for obesity, because their causes are multiple. Recently, the functional characterization of adipocytes, especially Beige adipocytes, has been of particular interest since their function is intimately related to the external circumstances of the environment and they have a flexibility that allows them to produce energy and improve many of the metabolic parameters in individuals. In the present manuscript we will focus on the characteristics of fat cells and their influence on cardiovascular risk.

Los colores del tejido adiposo / The colors of adipose tissue

Resumen El tejido adiposo es un órgano endocrino con gran actividad metabólica. A la fecha se han descubierto innumerables adipocinas y lipocinas, péptidos y lípidos con actividad biológica, secretadas por el tejido adiposo. Se sabe que tanto el tejido adiposo blanco como el pardo y el beige contribuyen a la homeostasis energética y a la regulación metabólica. Esta revisión tiene como finalidad comunicar los hallazgos más recientes relativos al tejido adiposo según su color y la relación de este con las alteraciones metabólicas asociadas a la obesidad. Después de la revisión de la literatura especializada, se identificó que en una misma estructura pueden coexistir poblaciones blancas, pardas y beige, que modifican el estado metabólico global en situaciones fisiológicas o patológicas.

Abstract Adipose tissue is an endocrine organ with high metabolic activity. Countless adipose tissue-secreted adipokines and lipokines, as well as peptides and lipids with biological activity have thus far been discovered. Both white and brown and beige adipose tissue are known to contribute to energy homeostasis and metabolic regulation. The purpose of this review is to report on the most recent findings related to adipose tissue according to its color and its relationship with metabolic alterations associated with obesity. After a review of the specialized literature, white, brown and beige adipocyte populations were identified to be able to coexist within the same structure, and to modify global metabolic state in physiological or pathological situations.

Research Progress of Celastrol in Obesity / 中国药学杂志

Obesity is a kind of metabolic disease, which is a major risk factor of heart disease, diabetes mellitus and cancer. In recent years, the US Food and Drug Administration (FDA) has approved a stand of drugs treatment for obesity, including sibutramine, orlistat, belviq and so on,however, side effects may occur after long-term using. Celastrol is a class of pentacyclic triterpenoids extracted from the roots of Tripterygium wilfordii Hook F. It has been found that celastrol has the pharmacological activities of increasing leptin sensitivity, increasing fat metabolism, inhibiting the formation of lipocyte and inhibiting chronic inflammation in obesity animals. This overview summarizes the related mechanisms of celastrol on treatment of obesity to provide enlightenments for its further study.