Relationship between skeletal muscle mass index and metabolic phenotypes of obesity in adolescents / 中国当代儿科杂志

OBJECTIVES@#To study the relationship between skeletal muscle mass index (SMI) and metabolic phenotypes of obesity in adolescents, and to provide a basis for the prevention and control of adolescent obesity and related metabolic diseases.@*METHODS@#A total of 1 352 adolescents aged 12 to 18 years were randomly selected by stratified cluster sampling in Yinchuan City from October 2017 to September 2020, and they were surveyed using questionnaires, physical measurements, body composition measurements, and laboratory tests. According to the diagnostic criteria for metabolic abnormalities and the definition of obesity based on the body mass index, the subjects were divided into four metabolic phenotypes: metabolically healthy normal weight, metabolically healthy obesity, metabolically unhealthy normal weight, and metabolically unhealthy obesity. The association between SMI and the metabolic phenotypes was analyzed using multivariate logistic regression.@*RESULTS@#The SMI level in the metabolically unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity groups was lower than that in the metabolically healthy normal weight group (P<0.001). Multivariate logistic regression analysis showed that after adjusting for gender and age, a higher SMI level was a protective factors for adolescents to develop metabolic unhealthy normal weight, metabolically healthy obesity, and metabolically unhealthy obesity phenotypes (OR=0.74, 0.60, and 0.54, respectively; P<0.001).@*CONCLUSIONS@#Increasing SMI can reduce the risk of the development of metabolic unhealthy/obesity.

Joint Association of Metabolic Health and Obesity with Ten-Year Risk of Cardiovascular Disease among Chinese Adults / 生物医学与环境科学（英文）

OBJECTIVE@#This study aims to investigate the association of metabolic phenotypes that are jointly determined by body mass index (BMI) or fat mass percentage and metabolic health status with the ten-year risk of cardiovascular disease (CVD) among Chinese adults.@*METHODS@#Data were obtained from a cross-sectional study. BMI and body fat mass percentage (FMP) combined with the metabolic status were used to define metabolic phenotypes. Multiple linear regression and logistic regression were used to examine the effects of metabolic phenotypes on CVD risk.@*RESULTS@#A total of 13,239 adults aged 34-75 years were included in this study. Compared with the metabolically healthy non-obese (MHNO) phenotype, the metabolically unhealthy non-obese (MUNO) and metabolically unhealthy obese (MUO) phenotypes defined by BMI showed a higher CVD risk [odds ratio, OR (95% confidence interval, CI): 2.34 (1.89-2.89), 3.45 (2.50-4.75), respectively], after adjusting for the covariates. The MUNO and MUO phenotypes defined by FMP showed a higher CVD risk [ OR (95% CI): 2.31 (1.85-2.88), 2.63 (1.98-3.48), respectively] than the MHNO phenotype. The metabolically healthy obese phenotype, regardless of being defined by BMI or FMP, showed no CVD risk compared with the MHNO phenotype.@*CONCLUSION@#General obesity without central obesity does not increase CVD risk in metabolically healthy individuals. FMP might be a more meaningful factor for the evaluation of the association of obesity with CVD risk. Obesity and metabolic status have a synergistic effect on CVD risk.

Asociación entre variables ecográficas de adiposidad abdominal y variables analíticas y antropométricas aplicando análisis de correlación canónica en gestantes normopeso / Association between echography variables of abdominal adiposity and analytical and anthropometric variables applying canonical correlation analysis in normal-weight pregnant

RESUMEN Fundamento: La obesidad abdominal en gestantes es un marcador de riesgo cardiometabólico independientemente de la adiposidad general, siendo la ultrasonografía de gran utilidad para distinguir los compartimientos adiposos del abdomen y diagnosticar tal peligro al inicio de la gestación. Objetivo: Determinar asociaciones entre variables ecográficas de adiposidad abdominal y variables analíticas y antropométricas en gestantes normopeso al inicio del embarazo según fenotipos metabólicos empleando análisis de correlación canónica. Metodología: Estudio transversal en 526 embarazadas normopeso, entre 12 y 14 semanas de edad gestacional, atendidas en consulta de ultrasonido del Policlínico Docente Chiqui Gómez, municipio Santa Clara. Se midieron las grasas abdominales subcutánea, preperitoneal y visceral, así como variables antropométricas y analíticas. Se conformaron 3 fenotipos metabólicos, y se aplicó la correlación canónica para determinar el nexo entre las mismas y su comportamiento en los diferentes fenotipos. Resultados: Se identificaron 2 conjuntos de variables con correlaciones canónicas que se incrementaron del fenotipo saludable al metabólicamente obeso con valores de 0.6930 a 0.8955 y 0.9298 respectivamente y alta significancia estadística (p=0.000). Conclusiones: Se demuestra el nexo entre las variables ecográficas de adiposidad abdominal grasa subcutánea y grasa visceral y las variables analíticas resistencia a Ia insulina, producto de acumulación lipídico, índice aterogénico y glucemia, evidenciado por los altos valores de correlaciones canónicas obtenidos según cambia el fenotipo de normopeso saludable al metabólicamente obeso; orientando un nuevo enfoque en la determinación de fenotipos de riesgo metabólico en la gestación temprana en mujeres normopeso.

ABSTRACT Background: Abdominal obesity in pregnant women is an indicator of cardiometabolic risk with non-independence of general adiposity, being the ultrasound very useful to distinguish the abdomen adipose compartments also diagnose this risk at the beginning of pregnancy. Objective: To determine possible associations between the ultrasound variables of abdominal adiposity and those analytical and anthropometric in normal-weight pregnant women at the beginning of pregnancy according to metabolic phenotypes using canonical correlation analysis. Methodology: A cross-sectional study in 526 normal-weight pregnant women, between 12 and 14 weeks of gestational age, assisted in the ultrasound office at Chiqui Gómez teaching polyclinic, in Santa Clara city. Subcutaneous, preperitoneal and visceral abdominal fats were measured, as well as anthropometric and analytical variables. Three metabolic phenotypes were formed, and canonical correlation was applied to determine their relation and also behavior among the different phenotypes. Results: 2 sets of variables were identified with canonical correlations that increased from the healthy to the metabolically obese phenotype with values from 0.6930 to 0.8955 and 0.9298 respectively and high statistical significance (p=0.000). Conclusions: The link between the ultrasound variables of abdominal adiposity, subcutaneous and visceral fat and the analytical insulin resistance, lipid accumulation product, atherogenic index and blood glucose is demonstrated, evidenced by the high values of canonical correlations obtained as the phenotype changes from healthy normal-weight to metabolically obese; guiding a new approach in the resolve of the metabolic risk phenotypes in early gestation in normal-weight women.

Study on Gene Polymorphism Distribution of Clopidogrel Absorption and Metabolism Related Gene CYP2C19， ABCB1 and PON1 in Patients with Coronary Heart Disease in Xinjiang Uygur Autonomous Region / 中国药房

OBJECTIVE：To study the relationship of polymorphism of clopidogrel absorption and metabolism related genes CYP2C19（* 2，* 3，* 17），ABCB1 C3435T and PON1 Q192R in patients with coronary heart disease in Xinjiang Uygur Autonomous Region ，and to explore the characteristics of population and combined diseases. METHODS ：A total of 1 126 patients with coronary heart disease who underwent clopidogrel absorption and metabolism related gene testing during hospitalization in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2020 were included as the study subjects. The gender，age，body mass index （BMI），nationality and the proportion of combined with hypertension and diabetes were compared among different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. RESULTS ：Among 1 126 patients，1 126 had CYP2C19 * 2，* 3 and * 17 genotypes，1 109 had ABCB1 C3435T genotype and 1 123 had PON1 Q192R genotype. The distribution of each genotype was in line with Hardy-Weinberg balance （P＞0.05）. There were 66（5.86％）， com 459（40.76％），476（42.27％） and 125（11.10％）patients with CYP2C19 ultra-rapid metabolizer （UM）， extensive metabolizer（EM），intermediate metabolizer （IM）and poor metabolizer（PM），respectively. The proportion of patients with UM metabolism phenotype with BMI ＞24 was significantly higher than those of patients with IM and PM metabolism phenotypes （P＜0.05）. The proportion of Han nationality patients with UM metabolic phenotype was significantly lower than those of patients with EM ，IM and PM metabolic phenotypes （P＜0.05）；the proportion of Uygur nationality was significantly higher than that of patients with EM ，IM and PM metabolic phenotypes （P＜ 0.05）. There were 355，538 and 216 patients with ABCB1 C3435T wild-type（CC），heterozygous（CT）and mutant homozygous （TT）genotypes，respectively；the proportion of Han nationality in TT genotype patients was significantly lower than that in CC and CT genotype patients （P＜0.05），and the proportion of Uygur nationality was significantly higher than that in CC and CT genotype patients （P＜0.05）；the proportion of TT genotype patients with diabetes was significantly higher than that of patients with CT genotype （P＜0.05）. There were 365，519 and 239 patients with PON1 Q192R wild-type（GG），heterozygous（GA）and mutant homozygous （AA），respectively；the proportion of Han nationality in AA genotype patients was significantly lower than that in GG and GA genotype patients （P＜0.05），and the proportion of Uygur nationality was significantly higher than that of GG and GA genotype patients （P＜0.05）；the proportion of Han nationality and BMI ≤24 in patients with AA genotype were significantly lower than those with GA genotype （P＜0.05），and the proportion of Uygur nationality ，BMI＞24 and hypertension were significantly higher than those in GA genotype patients （P＜0.05）. CONCLUSIONS ：There are significant nationality differences among patients with different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. In addition，patients with BMI ＞24 account for high proportion among CYP2C19 UM metabolism genotype ；patients with diabetes account for high proportion among ABCB1 C3435T TT genotype ；patients with BMI ＞24 and hypertension account for high proportion among PON1 Q192R AA genotype.

Preoperative Metabolic Tumor Volume(2.5) Associated with Early Systemic Metastasis in Resected Pancreatic Cancer: A Transcriptome-Wide Analysis

BACKGROUND/AIMS: ¹⁸F-fluorodeoxyglucose-positron emission tomography (¹⁸F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancers. METHODS: From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study. Clinicopathological parameters and PET parameters were evaluated, and transcriptome-wide analysis was performed to identify the oncologic impact and molecular landscape of the metabolic phenotype of resectable pancreatic cancers. RESULTS: Preoperative metabolic tumor volume (MTV)(2.5) was significantly higher in the pN1 group compared to the pN0 group (11.1±11.2 vs 6.5±7.8, p=0.031). Higher MTV(2.5) values (MTV(2.5) ≥4.5) were associated with multiple lymph node metastasis (p=0.003), and the lymph node ratio was also significantly higher in resected pT3 pancreatic cancer with MTV(2.5) ≥4.5 compared to those with MTV(2.5) <4.5 (0.12±0.13 vs 0.05±0.08, p=0.001). Disease-specific survival of patients with MTV(2.5) <4.5 was better than that of patients with MTV(2.5) ≥4.5 (mean, 28.8 months; 95% confidence interval [CI], 40.1 to 57.0 vs mean, 32.6 months; 95% CI, 25.5 to 39.7; p=0.026). Patients with MTV(2.5) ≥4.5 who received postoperative adjuvant chemotherapy showed better survival outcomes than patients with MTV(2.5) ≥4.5 who did not receive adjuvant treatment in resected pT3 pancreatic cancers (p<0.001). Transcriptome-wide analysis revealed that tumors with MTV(2.5) ≥4.5 demonstrated significantly different expression of cancer-related genes reflecting aggressive tumor biology. CONCLUSIONS: Resectable pancreatic cancer with high MTV(2.5) is not only associated with lymph node metastasis but also early systemic metastasis. The molecular background of resectable pancreatic cancer with high MTV(2.5) may be associated with aggressive biologic behavior, which might need to be considered when managing resectable pancreatic cancers. Further study is mandatory.

Comparative analysis of basal locomotor activity-related metabolic phenotypes between C57BL/6 mice and ICR mice substrains derived from three different sources / 한국실험동물학회지

Animal model, as an indispensable tool for scientific purposes of biomedical researches and clinical application, is a commonly used in various researches. Regarding to this, it is necessary to establish the metabolic phenotype of animal model to minimize spurious interpretations and ensure a level of accuracy and reliability adequate for experimental research. However, the metabolic phenotype-related analysis within rodent strains derived from different source is nonexistent, especially in C57BL/6Korl mice and Korl:ICR mice (a domestic mouse strain). To compare the physiological and metabolic phenotypes over a period of time, we utilized the C57BL/6 mice (C57BL/6Korl, A:C57BL/6, and B:C57BL/6) and ICR mice (Korl:ICR, A:ICR, and B:ICR) derived from three different sources. Our data showed that average body weight, body temperature, food intake, and water consumption have a similar tendency among the C57BL/6 and ICR groups, except for the higher body weight of C57BL/6Korl mice over a period of time. Moreover, some significant differences was observed in adipose tissue mass and adipocyte size among the groups, with a higher tendency of C57BL/6Korl mice and Korl:ICR mice. Most importantly, resting metabolic rate (RMR) serves as an approximation of the metabolic phenotype showed no significant difference among the groups of C57BL/6 mice and ICR mice, except for the lower oxygen uptake of C57BL/6Korl mice compare to the A:C57BL/6 mice. Taken together, our data suggest that C57BL/6 mice and ICR mice derived from three different sources have an overall similar feature of physiological and metabolic phenotypes.

In vitro metabolism of anti-tumor compound E7 in different species of liver microsomes / 中国中药杂志

To investigate the metabolic stability of E7 in liver microsomes of human, Beagle dog, Cynomolgus monkey and SD rats, and compare the metabolic differences between different species. Selective chemical inhibitors were used to determine the effects of different inhibitors on E7 metabolic rate, and predict the main enzymes involved in E7 metabolism in rat liver microsomes. The experimental results showed that the in vitro half-lives (T1/2) of E7 in liver microsomes of human, dog, monkey and rats were 57.75, 69.30, 16.90,30.13 min respectively. Their intrinsic clearance rate was 0.004 8, 0.004 0, 0.016 4 and 0.009 2 mL•min⁻¹•mg⁻¹ respectively. Hence, it could be speculated that the metabolic rate of E7 was similarly slow in human and dog liver microsomes; while it was similarly fast in monkey and rat liver microsomes. There was significant difference in metabolic rate of E7 between different species. The results showed that CYP2E1, CYP2A6, CYP1A2 and CYP2D6 might participate in metabolism of E7, while the contribution of polymorphic CYP3A4 was small.

Metabolic stability and metabolic enzyme phaenotypes of lanceolatin B in liver microsomes of different species by UPLC-MS/MS / 中国中药杂志

To investigate the metabolic stability and parameters in vitro of lanceolatin B in liver microsomes of rats, human, Beagle dogs, and monkeys, and to identify the phaenotypes of CYP enzymes of lanceolatin B by using the liver microsome incubation system in vitro. After incubated with different species of liver microsomes, lanceolatin B was quantified by UPLC-MS/MS method to evaluate its metabolic stability and metabolic kinetic parameters in vitro. Lanceolatin B was incubated with specific inhibitors of CYP450 isoforms (CYP2E1, 2C19, 1A2, 2D6, 2C9, 3A4, and 2A1) to determine the phaenotypes of metabolic enzymes. The results showed that lanceolatin B was metabolized in the liver microsomes of rats and monkeys but not in the human and Beagle dogs. Their in vitro half-life T1/2 and intrinsic clearance rate CLint in rat and monkey liver microsomes were 11.57,8.07 min, and 0.12,0.17 mL•min⁻¹•mg⁻¹ without significant difference. The results of metabolic phenotyping indicated that CYP1A2 was mainly involved in the metabolism of lanceolatin B. There existed a difference in the metabolism of lanceolatin B in different types of liver microsomes. Several of CYP450 isoforms metabolized lanceolatin B together in liver microsomes of rats, in which CYP1A2 was the major enzyme mainly responsible for the metabolism of lanceolatin B.

CYP2E1 Genetic Polymorphism relating to Styrene Metabolism of Korean Workers / 대한산업의학회지

The goal of this study is to observe the associations between the metabolic phenotype by personal exposure and urinary metabolites and genetic polymorphism of CYP2E1 which is known to be related with styrene metabolism. To complete this study, the author executed a battery of tests on 46 workers who were working at laminating department of fiberglass- reinforced plastics (FRP) industry located in Pusan and Kyungnam area during April to June 1998. Those were - (1) personal exposure assessment with organic vapour monitor and gas chromatography. (2) measurement of urinary metabolites - mandelic acid (MA) and phenylglyoxylic acid (PGA) - with high performance liquid chromatography (HIPLC), (3) CYP2E1 genotying with PCR and restriction fragment length polymorphism (RFLP) using Dra I and Rsa I, and (4) questionnaire survey for some individual characteristics. Study subjects were composed of 32 men and 14 women, and whose average age was 39.4 years, average tenure was 7.7 years. Each concentration expressed by geometric mean(range) was as follows; air styrene 15.6(3.1-81.0) ppm, urinary MA 187.8(36.8-1007.2) mg/g creatinine, PGA 232.8(46.8-1075.7) mg/g creatinine. Correlation coefficients between air styrene were MA 0.54, PGA 0.37, MA+PGA 0.54 (p or= 0.063 and air styreneTLV-TWA/urinary MA+PGABEI >or= 0.048 was classified as poor metabolizer, and, the value of air styreneTLV-TWA/urinary MABEI~ 0.05), as in case of MA, mutant type 66.7% and wild type 48.0%, and in case of MA+PGA, mutant type 81.0% and wild type 56.0%. These results suggests that CYP2E1 mutant allele has a tendency toward the poor metabolizer. This study has several limitations as small sample size, and no considerations on work intensity, alcohol habit, obesity, etc which can affect styrene metabolism. However, this study is of value because this is first study to propose the fundamental data about associations between exposure level, biological monitoring, and CYP2E1 genetic polymorphism in Korean workers dealing with pure styrene. To improve accuracy of the study, that means, to applicate the result of this study on the personal risk assessment of styrene workers, larger sample size and consideration for confounders are needed.