ABSTRACT
AIM: ADRB3 DNA hypermethylation was recently associated with dyslipidemia in familial hypercholesterolemia (FH). In this study, we verified whether ADRB3 DNA methylation in blood and visceral adipose tissue (VAT) was associated with obesity and its related complications. METHODS: DNA methylation levels were measured in the blood of 61 FH men, and the blood and VAT of 30 severely obese men. Common ADRB3 polymorphisms were genotyped in all subjects. RESULTS: Higher ADRB3 DNA methylation levels were significantly associated with lower low-density lipoprotein cholesterol levels (r = -0.40; p = 0.01) in FH, and with a lower waist-to-hip ratio (r = -0.55; p = 0.01) and higher blood pressure (r = 0.43; p = 0.05) in severely obese men. ADRB3 g.-843C>T and p.W64R polymorphisms were found to be strongly associated (p < 0.001) with ADRB3 DNA methylation and mRNA levels. CONCLUSION: Although further studies are needed, these results suggest that epigenetic changes at the ADRB3 gene locus might be involved in the development of obesity and its related metabolic complications.
Subject(s)
DNA Methylation , Hyperlipoproteinemia Type II/genetics , Hypertension/genetics , Intra-Abdominal Fat/metabolism , Obesity, Morbid/genetics , Receptors, Adrenergic, beta-3/blood , Receptors, Adrenergic, beta-3/genetics , Cholesterol, LDL/metabolism , Epigenesis, Genetic , Genetic Association Studies , Genome, Human , Humans , Hyperlipoproteinemia Type II/pathology , Male , Obesity, Morbid/complications , Obesity, Morbid/pathology , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Quantitative Trait Loci , RNA, Messenger/genetics , Waist-Hip Ratio , White PeopleABSTRACT
The purpose of this study was to investigate whether the genetic polymorphisms of the uncoupling protein 1 (UCP1) and beta 3 adrenergic receptor (beta3-AR) were associated with differences in weight loss and lipid profiles in obese premenopausal women exposed to low-calorie meal replacements over a period of six weeks. Forty women between the ages of 20 and 35 were randomly divided into two groups, each of which consumed one of two low-calorie meal replacements containing either white rice or mixed rice. Although body weight, body mass index (BMI), blood glucose concentration, triglycerides, total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were not significantly different by the UCP1 genotype in the white rice group, there were significant differences in body weight (p = 0.041), BMI (p = 0.027), and blood glucose concentration (p = 0.047) between carriers and non-carriers of the G allele in the mixed rice group after the six-week meal replacement intervention. The beta3-AR polymorphism showed no apparent affect on these parameters. Dietary fiber affects weight gain since it is closely related with absorption of nutrients. As a result, the AA type UCP1 genotype produced significant weight loss in the mixed rice group, but not in the white rice group.
Subject(s)
Ion Channels/genetics , Lipids/blood , Mitochondrial Proteins/genetics , Obesity/blood , Polymorphism, Genetic/genetics , Receptors, Adrenergic, beta-3/genetics , Weight Loss/genetics , Adult , Blood Glucose , Body Mass Index , Body Weight , Diet, Reducing/methods , Dietary Fiber , Female , Humans , Ion Channels/blood , Lipids/genetics , Mitochondrial Proteins/blood , Obesity/genetics , Oryza , Receptors, Adrenergic, beta-3/blood , Uncoupling Protein 1 , Young AdultABSTRACT
OBJECTIVE: To investigate the effects of short term (15 days) cafeteria diet feeding on the expression of beta3-AR in vivo and its association with lipolytic stimulation induced by beta3-AR agonist CGP12177A in isolated white adipocytes. ANIMALS: Six female and 6 male Wistar rats (at 4 weeks of age) were fed on a cafeteria diet plus standard diet for 15 days. The remaining 12 age- and sex-matched rats always received standard diet only. MEASUREMENTS: White gonadal adipose tissue was isolated and used for the determination of beta3-AR and leptin expression, and for in vitro studies of lipolytic activity. RESULTS: Control male rats had higher levels of both beta3-AR and leptin mRNA in white adipose tissue than their female counterparts. Both male and female rats up-regulated the levels of both beta3-AR and leptin mRNA in response to 15 day cafeteria diet feeding. Noradrenaline- and isoprenaline-induced lipolysis were significantly increased in fat cells from control females compared to their male counterparts. CGP12177A stimulation resulted in significantly higher glycerol release in fat cells from cafeteria diet-fed female rats, whereas there were no differences due to dietary treatment in male rats. The maximal lipolytic response of forskolin (stimulating adenylyl cyclase) and dibutyryl cyclic AMP (cyclic AMP analogous) was not affected by sex or cafeteria diet feeding. CONCLUSION: Cafeteria diet feeding brings about higher excess body weight and impaired adipose tissue lipolytic activity in female rats compared to male rats. Thus, the higher levels of beta3-AR mRNA induced by cafeteria feeding are not indicative per se of an increase of the lipolytic response of the adipocytes. The changes seen in other adrenoceptor subtypes (beta1 and beta2) may be more determinant of the overall lipolytic response of adipocytes.
