Screening for Melanocortin 4 Receptor Mutations in Chinese Extremely Obese Individuals

Accumulating evidence indicates that overweight and obesity are the major international public health concern. Obesity is a major independent risk factor for chronic diseases, such as hypertension, type 2 diabetes, cardiovascular disease, stroke, and certain cancer. Disease burden due to obesity has been dramatically increasing in many countries including China in the past years. According to the Nationwide Health and Nutrition Survey （CHNS）, the prevalence of overweight and obesity among men and women in China increased by 27.6% and 8.8%, respectively, from 1993 to 2009.

Obesity is associated with the Arg389Gly ADRB1 but not with the Trp64Arg ADRB3 polymorphism in children from San Luis Potosí and León,México

This research was designed to analyze the possible associations of Arg389 Gly ADRB1 and Trp64 Arg ADRB3polymorphisms in children with obesity.A cross-sectional study included 1,046 school-age Mexican participants（6-12 years old） from the cities of San Luis Potosi and Leon.Children were classified as non-obese or obese according to their body mass index（BMI） percentile;obese children had a BMI≥95th percentile for sex and age.Biochemical data were collected.Polymorphisms were detected using TaqMan qPCR assay.A logistic regression analysis was used to calculate the risk of obesity based on genotypes.Differences were found between groups where obese children had a significant increase in systolic and diastolic blood pressure,fasting plasma glucose,insulin,HOMAIR,LDL-cholesterol,triglycerides,and lower HDL-cholesterol compared with the normal weight group（P 〈 0.05）.The distribution of allele frequency in the population was Arg = 87.4 and Gly = 12.6（Hardy Weinberg equilibrium x^2= 3.16,P = 0.07）;Trp = 81.5 and Arg= 18.5（Hardy Weinberg equilibrium x^2 = 2.2,P = 0.14） for ADRB1 and ADRB3,respectively.Even though no different frequencies of Arg389 Gly polymoiphism between groups were found（P = 0.08）,children carriers of one Gly389,ADRB1 allele had a risk for obesity of OR = 1.40（95%CI,1.03-1.90,P =0.03） after adjustment for age and gender.No other association was found for Trp64 Arg ADRB3 polymorphism.Only the Arg389 Gly ADRB1 polymorphism was associated with risk for obesity in Mexican children.

IFN-γ Secretion in Gut of Ob/Ob Mice after Vertical Sleeve Gastrectomy and Its Function in Weight Loss Mechanism

Vertical sleeve gastrectomy（VSG） is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon（IFN）-γ secretion n of mesenteric lymph nodes in obese mice（ob/ob mice）, a model of VSG, and its relationship with farnesoid X receptor（FXR） expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type（WT） mice and ob/ob mice were divided into four groups： A（WT＋Sham）, B（WT＋VSG）, C（ob/ob＋Sham）, and D（ob/ob＋VSG）. Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry（FCM）. The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from（40.6±2.7） g to（27.5±3.8） g on the 30 th day after VSG（P〈0.05）. At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation（P〈0.05）. The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively（P〈0.05）. After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ（0, 10, 25, 50, 100, and 200 ng/m L）, the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation（P〈0.05）. It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.