Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smith-Magenis syndrome (SMS) is a genetic disorder caused by haploinsufficiency of the retinoic acid induced 1 (RAI1) gene. In addition to intellectual disabilities, behavioral abnormalities and sleep disturbances, a majority of children with SMS also have significant early-onset obesity. To study the role of RAI1 in obesity, we investigated the growth and obesity phenotype in a mouse model haploinsufficient for Rai1. Data show that Rai1(+/-) mice are hyperphagic, have an impaired satiety response and have altered abdominal and subcutaneous fat distribution, with Rai1(+/-) female mice having a higher proportion of abdominal fat when compared with wild-type female mice. Expression analyses revealed that Bdnf (brain-derived neurotrophic factor), a gene previously associated with hyperphagia and obesity, is downregulated in the Rai1(+/-) mouse hypothalamus, and reporter studies show that RAI1 directly regulates the expression of BDNF. Even though the Rai1(+/-) mice are significantly obese, serum analyses do not reveal any evidence of metabolic syndrome. Supporting these findings, a caregiver survey revealed that even though a high incidence of abdominal obesity is observed in females with SMS, they did not exhibit a higher incidence of indicators of metabolic syndrome above the general population. We conclude that Rai1 haploinsufficiency represents a single-gene model of obesity with hyperphagia, abnormal fat distribution and altered hypothalamic gene expression associated with satiety, food intake, behavior and obesity. Linking RAI1 and BDNF provides a more thorough understanding of the role of Rai1 in growth and obesity and insight into the complex pathogenicity of obesity, behavior and sex-specific differences in adiposity.
 ...
PMID:Rai1 haploinsufficiency causes reduced Bdnf expression resulting in hyperphagia, obesity and altered fat distribution in mice and humans with no evidence of metabolic syndrome. 2066 24

Genome-wide association studies have revealed several gene variants associated with obesity; however, only a few studies have further investigated their association with metabolic syndrome. We performed a study of eleven variants in/near genes TMEM18, SH2B1, KCTD15, PCSK1, BDNF, SEC16B, MC4R, and FTO in Czech adolescents and analysed their association with obesity, metabolic syndrome and related traits. Genotyping was performed in 1,443 adolescents aged 13.0-17.9 years. Anthropometric parameters, biochemical parameters and blood pressure were assessed. Metabolic syndrome was defined according to the International Diabetes Federation. The FTO rs9939609 variant was associated with overweight/obesity (OR 1.40, 95% CI 1.21-1.63, P < 0.001). The minor allele of TMEM18 rs7561317 was related to underweight (OR 1.78, 95% CI 1.14-2.79, P = 0.015). BDNF rs925946 and MC4R rs17782313 were associated with metabolic syndrome (OR 1.53, 95% CI 1.14-2.04, P = 0.005; 1.51, 95% CI 1.12-2.04, P = 0.009). The PCSK1 rs6235 variant was negatively related to increased blood glucose (OR 0.69, 95% CI 0.49-0.97, P = 0.040). In conclusion, the FTO variant was associated with overweight/obesity in Czech adolescents. Moreover, MC4R and BDNF variants increased the risk of metabolic syndrome, probably through their effect on abdominal obesity. The PCSK1 variant may have a protective role in the development of type 2 diabetes.
...
PMID:Association of obesity susceptibility gene variants with metabolic syndrome and related traits in 1,443 Czech adolescents. 2389 Apr 80

The current case-control study sought the association of BDNF rs6265 and MC4R rs17782313 with metabolic syndrome (MetS), MetS components and other related metabolic parameters in a sample of Pakistani subjects. Fasting high-density lipoprotein cholesterol (HDL-C) and homeostatic model assessment of insulin sensitivity showed a significantly lower mean whereas body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglycerides (TG), cholesterol to HDL-C ratio, TG to HDL-C ratio, homeostatic model assessment of insulin resistance, visceral adiposity index, lipid accumulation product and the product of TG and glucose showed a significantly higher mean in the presence of MetS. Reduced HDL-C appeared as the most frequent and hypertriglyceridemia as the least frequent component of MetS whereas clustering of reduced HDL-C + abdominal obesity (AO) + hyperglycemia appeared as the most prevalent combination of MetS components. Moreover, BDNF rs6265 showed BMI and gender independent association with increased risk of MetS in Pakistani individuals whereas MC4R rs17782313 showed BMI and gender dependent association with increased risk of MetS in Pakistani females. In addition, BDNF rs6265 and MC4R rs17782313 showed gender-dependent associations with decreased risk of having low HDL-C in males and increased risk of having abdominal obesity in females, respectively. However, no association was observed for metabolic variables other than components of MetS across genotypes of both BDNF rs6265 and MC4R rs17782313.
 ...
PMID:Association of BDNF rs6265 and MC4R rs17782313 with metabolic syndrome in Pakistanis. 3150 73