BioProject

The prevalence of obesity has been increasing rapidly worldwide during the past two decades. More...

The prevalence of obesity has been increasing rapidly worldwide during the past two decades. This is alarming, since obesity has considerable effects on morbidity and mortality. The majority of gene expression studies about the effect of obesity and weight loss have been performed using the adipose tissue for mRNA extraction. However, also the liver plays a central role in maintaining energy balance. To our knowledge, no overall analysis of hepatic gene expression in response to changes in nutritional status has been made in humans Therefore, it is important to investigate how a short-time hypocaloric diet affects overall hepatic gene expression and the metabolic profile in a group of overweight and obese women. The subjects (n=31) were middle-aged, overweight (BMI>25 kg/m2) women with gallstone disease scheduled for an elective gallbladder operation. The intervention subjects were placed on a hypocaloric AHA step I diet with a recommended daily energy intake of 5.0 MJ. The objective was to reduce 0.5 kg of body weight per week. The control subjects were instructed to continue their habitual diet and not to lose weight. Basic clinical measurements and laboratory analyses were performed twice at baseline and at two week intervals during the weight reduction period. Surgical liver biopsies were obtained at the end of the weight reduction period. RNA samples of 4 individuals from the intervention group and 4 individuals from the control group were selected for the microarray analysis. The results from the microarray analysis were fairly surprising. Only one gene was up-regulated and the rest 142 down-regulated in the diet intervention group compared to the control group when a minimum of 2-fold change was set as the limit. The global decrease in hepatic gene expression was unexpected but the results are interesting, with several genes not previously linked to weight reduction. The decrease in triglyceride and fasting plasma insulin concentrations observed in our study is in accordance with results from many previous weight-loss trials. Keywords: Overall hepatic gene expression associated with obesity and moderate weight loss in a group of overweight and obese middle-aged women. Overall design: The subjects (n=31) were middle-aged, overweight (BMI>25 kg/m2) women with gallstone disease scheduled for an elective gallbladder operation in 4-8 weeks. Before the weight reduction period all the study subjects visited the laboratory twice. They consumed their habitual diets and seven-day food consumption records were collected and checked by an experienced dietitian. The weight reduction program was based on dietary counseling. The intervention subjects (n=12) were placed on a hypocaloric AHA step I diet with a recommended daily energy intake of 5.0 MJ. The objective was to reduce 0.5 kg of body weight per week. The control subjects (n=19) were instructed to continue their habitual diet and not to lose weight. During the study period, the subjects visited the laboratory at two week intervals for a clinical follow-up, fasting blood sample collection and body weight recording on all occasions. At the end of the study, surgical liver biopsies were obtained during gallstone operation, flash-frozen in liquid nitrogen and kept at -70°C until RNA extraction. Total RNA was extracted from liver tissue and RNA concentration and purity were assessed spectrophotometrically at wavelengths 260 and 280 nm. RNA integrity was checked by agarose gel electrophoresis. RNA samples of 4 individuals from the intervention group and 4 individuals from the control group were selected for the microarray analysis. The individuals from the diet intervention group were selected to represent the whole group, not just those who lost most weight. The microarray data was validated by performing relative quantitative real-time (RT) PCR using liver samples from 7 intervention subjects and 8 control subjects, including the samples used in the microarray analysis. 11 genes were selected on the basis of biological interest. The expression of these genes was concordant with the microarray data Less...