A microarray search for genes predominantly expressed in human omental adipocytes: adipose tissue as a major production site of serum amyloid A.

To identify genes predominantly expressed in omental adipocytes, microarray expression profiles from 33 human tissues or cell types were analyzed, using an algorithm developed for identification of transcripts predominantly expressed in a certain tissue. Both known adipocyte-specific and more unexpected genes were among the 28 genes identified. To validate the approach, adipocyte expression of three of these genes, acute-phase serum amyloid A (A-SAA), aquaporin 7, and transport secretion protein-2.2, was compared with 17 other human tissues by real-time PCR. The unexpectedly high expression of A-SAA in adipocytes was further verified by Northern blot and immunohistochemistry. The liver, reported to be the main production site for A-SAA, displayed the second highest expression using microarray and real-time PCR. In obese subjects, adipose tissue mRNA and serum A-SAA levels were down-regulated during an 18-wk diet regime (P < 0.05 and P < 0.0001, respectively). A-SAA serum levels were highly correlated to adipose tissue mRNA levels (P < 0.001) and to the total (P < 0.0001) and sc (P < 0.0001) adipose tissue areas, as analyzed by computed tomography. We show that adipose tissue is a major expression site of A-SAA during the nonacute-phase reaction condition. This provides a direct link between adipose tissue mass and a marker for low-grade inflammation and cardiovascular risk.

XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients.

OBJECTIVE: It is well established that the risk of developing type 2 diabetes is closely linked to the presence and duration of overweight and obesity. A reduction in the incidence of type 2 diabetes with lifestyle changes has previously been demonstrated. We hypothesized that adding a weight-reducing agent to lifestyle changes may lead to an even greater decrease in body weight, and thus the incidence of type 2 diabetes, in obese patients. RESEARCH DESIGN AND METHODS: In a 4-year, double-blind, prospective study, we randomized 3,305 patients to lifestyle changes plus either orlistat 120 mg or placebo, three times daily. Participants had a BMI >/=30 kg/m2 and normal (79%) or impaired (21%) glucose tolerance (IGT). Primary endpoints were time to onset of type 2 diabetes and change in body weight. Analyses were by intention to treat. RESULTS: Of orlistat-treated patients, 52% completed treatment compared with 34% of placebo recipients (P < 0.0001). After 4 years' treatment, the cumulative incidence of diabetes was 9.0% with placebo and 6.2% with orlistat, corresponding to a risk reduction of 37.3% (P = 0.0032). Exploratory analyses indicated that the preventive effect was explained by the difference in subjects with IGT. Mean weight loss after 4 years was significantly greater with orlistat (5.8 vs. 3.0 kg with placebo; P < 0.001) and similar between orlistat recipients with impaired (5.7 kg) or normal glucose tolerance (NGT) (5.8 kg) at baseline. A second analysis in which the baseline weights of subjects who dropped out of the study was carried forward also demonstrated greater weight loss in the orlistat group (3.6 vs. 1.4 kg; P < 0.001). CONCLUSIONS: Compared with lifestyle changes alone, orlistat plus lifestyle changes resulted in a greater reduction in the incidence of type 2 diabetes over 4 years and produced greater weight loss in a clinically representative obese population. Difference in diabetes incidence was detectable only in the IGT subgroup; weight loss was similar in subjects with IGT or NGT [correction].

Musculoskeletal pain in the obese: a comparison with a general population and long-term changes after conventional and surgical obesity treatment.

Obesity is associated with musculoskeletal pain and osteoarthritis. This study compares the prevalence of work-restricting musculoskeletal pain in an obese and a general population and investigates changes in the incidence of and recovery from musculoskeletal pain after bariatric surgery or conventional obesity treatment. A random sample of 1135 subjects from a general population was compared with 6328 obese subjects in the Swedish obese subjects (SOS) study. For the obese subjects, information about musculoskeletal pain was also collected 2 and 6 years after obesity surgery or the start of non-surgical treatment. In both sexes, self-reported work-restricting pain in the neck and back area and in the hip, knee and ankle joints was more common in the obese subjects than in the general population (odds ratios (ORs) ranging from 1.7 to 9.9, P<0.001). Operated obese women had a lower incidence of work-restricting pain in the knee and ankle joints compared with the conventionally treated control group over 2 and 6 years (ORs 0.51-0.71). Among subjects reporting symptoms at baseline, the recovery rate for pain in the knee and ankle joints in men and pain in the neck and back and in the hip, knee and ankle joints in women improved in the surgical group compared with the control group after 2 years (ORs 1.4-4.8). Obese subjects have more problems with work-restricting musculoskeletal pain than the general population. Surgical obesity treatment reduces the long-term risk of developing work-restricting musculoskeletal pain and increases the likelihood of recovering from such pain.

Copper induces the expression of cholesterogenic genes in human macrophages.

Accumulation of lipids and cholesterol by macrophages and subsequent transformation into foam cells are key features in development of atherosclerosis. Serum copper concentrations have been shown to be associated with cardiovascular disease. However, the mechanism behind the proatherogenic effect of copper is not clear. We used DNA microarrays to define the changes in gene expression profile in response to copper exposure of human macrophages. Expression monitoring by DNA microarray revealed 91 genes that were regulated. Copper increased the expression of seven cholesterogenic genes (3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase, IPP isomerase, squalene synthase, squalene epoxidase, methyl sterol oxidase, H105e3 mRNA and sterol-C5-desaturase) and low-density lipoprotein receptor (LDL-R), and decreased the expression of CD36 and lipid binding proteins. The expression of LDL-R and HMG CoA reductase was also investigated using real time PCR. The expression of both of these genes was increased after copper treatment of macrophages (P<0.01 and P<0.01, respectively). We conclude that copper activates cholesterogenic genes in macrophages, which may provide a mechanism for the association between copper and atherosclerosis. The effect of copper on cholesterogenic genes may also have implications for liver steatosis in early stages of Wilson's disease.

Coping and distress: what happens after intervention? A 2-year follow-up from the Swedish Obese Subjects (SOS) study.

OBJECTIVE: The study examined effects of weight change on coping and distress in severely obese subjects treated conventionally or undergoing weight reduction surgery. METHODS: We used the Obesity Coping (OC) scale measuring emotion-focused, maladaptive coping (Wishful Thinking) and problem-focused, adaptive coping (Social Trust and Fighting Spirit). We also used the Obesity Distress (OD) scale (Intrusion and Helplessness) and the Hospital Anxiety and Depression (HAD) scale. A total of 1146 surgical candidates and 1085 conventionally treated patients completed the OC and OD before treatment and after 24 months. RESULTS: Weight gainers reduced their use of both problem- and emotion-focused coping, thus leaving distress levels unchanged. All participants who lost weight decreased in emotion-focused coping and distress. Participants losing 20 kg or more also increased in problem-focused coping, resulting in even greater improvements regarding distress. CONCLUSIONS: Two years after starting treatment, the pattern and magnitude of change in coping and distress was the same irrespective of type of treatment and was, instead, related to the amount of weight change (the more weight change the greater the changes in coping and distress). Increases in problem-focused coping required major weight reduction, whereas minor weight gain led to a decrease. Emotion-focused coping decreased irrespective of direction of weight change, suggesting a general intervention effect of receiving professional help and support. These results have implications concerning behavior-based interventions of obese patients.

Long-term effect of bariatric surgery on liver enzymes in the Swedish Obese Subjects (SOS) study.

BACKGROUND AND AIM: Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals. METHODS: The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups. RESULTS: Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up. CONCLUSIONS: Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals.

Spouse resemblance in body mass index: effects on adult obesity prevalence in the offspring generation.

Accruing evidence indicates that mate selection is promoted by similarity in body fatness. Assortative mating for obesity may contribute genetically to the obesity epidemic by increasing the risk in subsequent generations. To test this hypothesis, the authors analyzed measured and validated questionnaire data on family members, obtained between 1987 and 2000 from 7,834 obese probands and from 829 subjects randomly ascertained from the general Swedish population. Spouse correlations in body mass index were strongest among couples with the shortest duration of cohabitation. Obesity concordance in parents was associated with an obesity prevalence of 20.1% in adult offspring compared with 1.4% if parents were concordantly nonobese (odds ratio = 18.3, 95% confidence interval: 9.0, 37.4). The prevalence was 8.2% if parents were obesity discordant (odds ratio = 6.5, 95% confidence interval: 3.2, 13.2). No association was found between rearing parents' and nonbiologic offspring's body mass index. These results agree with the hypothesis that assortative mating for obesity confers a higher risk of obesity in the offspring generation and thus contributes to the obesity epidemic. Parental obesity concordance is a strong, easily identifiable genetic risk factor that should be considered in the complex network of risk factors for obesity in designing primary prevention programs.

Effort-related calf pain in the obese and long-term changes after surgical obesity treatment.

OBJECTIVE: To compare the prevalence of effort-related calf pain in an obese and a general population and to analyze the incidence of and recovery from such pain after surgical and conventional obesity treatment. RESEARCH METHODS AND PROCEDURES: A random sample of 1135 subjects from a general population was compared with 6328 obese subjects in the Swedish Obese Subjects study. Obese subjects were followed longitudinally, and information about calf pain was obtained from surgically and conventionally treated patients for up to 6 years. RESULTS: In both sexes, self-reported calf pain was more common in the obese than in the general population [odds ratios (ORs) 5.0 and 4.0 in men and women, respectively, p<0.001]. Obese patients undergoing surgery had a lower 6-year incidence of calf pain compared with the conventionally treated control group (ORs 0.39 and 0.61, p<0.05). Among subjects reporting symptoms at baseline, the 6-year recovery rate was higher in the surgical group compared with the control group (ORs 15.3 and 5.9, p<0.001). DISCUSSION: Obese subjects have markedly more problems with effort-related calf pain than the general population. Surgical obesity treatment reduces the long-term risk of developing claudication symptoms and increases the likelihood of recovering from such symptoms.