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Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations. [ABSTRACT FROM AUTHOR]

Ghrelin, the only known appetite-stimulating hormone in humans, may be one factor involved in increased appetite, cravings and food intake following weight loss. Innovative strategies for suppressing ghrelin and decreasing appetite during weight loss maintenance are needed. Recent research has highlighted relationships between ghrelin, stress and lifestyle factors. The purposes of the current review are to (i) describe the current status of knowledge about ghrelin and lifestyle factors; (ii) critically examine research in this area, highlighting inconsistencies and methodological issues and (iii) discuss future directions and implications for obesity treatment. Based on Literature search using PsycINFO and Medline databases, we reviewed experimental studies on relationships between ghrelin, stress, exercise and sleep. Ghrelin levels are positively related to stress hormones, and stress management interventions including exercise and sleep may help to reduce acylated ghrelin and corresponding appetite. Behavioural interventions may offer a practical, cost-effective alternative for reducing or stabilizing ghrelin levels after initial weight loss. Adding behavioural techniques designed to reduce ghrelin to traditional weight loss maintenance protocols may help individuals to maintain weight loss. Future directions for investigating relationships between ghrelin and behavioural factors, examining the efficacy of behavioural programmes in reducing ghrelin and improving weight loss maintenance are discussed. [ABSTRACT FROM AUTHOR]

Drugs that improve chronic hyperglycemia independently of insulin signaling or reduction of adiposity or dietary fat intake may be highly desirable. Ad36, a human adenovirus, promotes glucose uptake in vitro independently of adiposity or proximal insulin signaling. We tested the ability of Ad36 to improve glycemic control in vivo and determined if the natural Ad36 infection in humans is associated with better glycemic control. C57BL/6J mice fed a chow diet or made diabetic with a high-fat (HF) diet were mock infected or infected with Ad36 or adenovirus Ad2 as a control for infection. Postinfection (pi), systemic glycemic control, hepatic lipid content, and cell signaling in tissues pertinent to glucose metabolism were determined. Next, sera of 1,507 adults and children were screened for Ad36 antibodies as an indicator of past natural infection. In chow-fed mice, Ad36 significantly improved glycemic control for 12 wk pi. In HF-fed mice, Ad36 improved glycemic control and hepatic steatosis up to 20 wk pi. In adipose tissue (AT), skeletal muscle (SM), and liver, Ad36 upregulated distal insulin signaling without recruiting the proximal insulin signaling. Cell signaling suggested that Ad36 increases AT and SM glucose uptake and reduces hepatic glucose release. In humans, Ad36 infection predicted better glycemic control and lower hepatic lipid content independently of age, sex, or adiposity. We conclude that Ad36 offers a novel tool to understand the pathways to improve hyperglycemia and hepatic steatosis independently of proximal insulin signaling, and despite a HF diet. This metabolic engineering by Ad36 appears relevant to humans for developing more practical and effective antidiabetic approaches. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify mechanisms through which valproic acid (VPA) causes weight gain. Healthy participants (N = 52) were randomized to VPA or placebo in a double-blind study. Energy intake (EI) was measured in the laboratory at lunch and dinner, and physical activity (PA) was measured with accelerometry. Glucose levels and hormones [Peptide YY3-36, glucagon-like peptide-1 (GLP-1), leptin, ghrelin, insulin] that regulate EI were measured. Assessments occurred at baseline and week 3. Change from baseline was evaluated with mixed models (α = 0.05). Weight significantly increased in the VPA group (+0.49 kg), but not the placebo group. The VPA group increased fast food fats cravings and decreased glucose levels compared with placebo. Change in weight, EI and PA did not differ by group. Within group analyses indicated that the VPA group increased PA, hunger, binge eating, depression and GLP-1. VPA-associated weight gain is not likely due to changes in PA or the gut hormones studied. Although EI did not increase when measured after 3 weeks of treatment, VPA decreased glucose levels and increased motivation to eat; hence, EI might have increased in the short-term. Research testing VPA on short-term (1 week) EI, metabolism, and substrate partitioning is warranted. [ABSTRACT FROM AUTHOR]

Objective: The sympathetic nervous system and thiazolidinediones control lipid metabolism and have been implicated in body weight regulation. This study was conducted to determine whether the simultaneous activation of these two signaling systems might synergize to exert beneficial effects on the expression of key genes involved in lipid metabolism and mitochondrial biogenesis in subcutaneous fat in nondiabetic subjects.Research Design and Methods: A total of 57 women and men were randomized into four groups: 1) placebo/placebo (PP), 2) ephedrine HCl (25 mg, 3 times daily) plus caffeine (200 mg, 3 times daily)/placebo (ECP), 3) placebo/pioglitazone (45 mg) (PPio), and 4) ephedrine plus caffeine/pioglitazone (ECPio) for 16 weeks. Adipose tissue samples were obtained after 12 weeks of treatment to determine gene expression.Results: Body fat decreased by 6.0 and 4.6% in the ECP and ECPio groups, respectively, while remaining unchanged in the PPio and PP groups. Triglyceride levels decreased by -7.7, -24, -15.2, and -41 mg/dl after 16 weeks treatment in the PP, PPio, ECP, and ECPio groups, respectively. This indicates that pioglitazone groups with or without EC (ephedrine HCl plus caffeine) decreased triglycerides, and EC groups with or without pioglitazone decreased body weight. The mRNA for sirtuin 1 and CD36 increased only in the ECPio group. Carnitine palmitoyltransferase-1, medium-chain acyl CoA dehydrogenase, and malonyl-CoA decarboxylase increased with PPio and ECPio. Stearoyl-CoA desaturase decreased with ECP.Conclusions: Combined activation of peroxisome proliferator-activated receptor-gamma and beta-adrenergic receptors has beneficial effects on body weight, plasma triglycerides, and lipid metabolism in subcutaneous fat by increasing the expression of genes required for fatty acid catabolism. [ABSTRACT FROM AUTHOR]

Objective: A human pilot study testing the safety and effectiveness of NT (Number Ten), a dietary herbal supplement made from rhubarb, ginger, astragulus, red sage and turmeric, to reduce food intake and cause weight loss.Research Methods and Procedures: A total of 24 healthy women, 18-60 years, body mass index 25-35 kg/m(2) on no chronic medication were randomized to four groups of six: (1) oral freeze-dried NT 6 gm/day, (2) bed-dried NT 6 gm/day, (3) freeze-dried NT 12 gm/day or (4) placebo. Number Ten dose was escalated over 3 weeks and maintained for 8 weeks on a 700 kcal/day diet below maintenance. Food intake was measured at baseline and 4 weeks. Safety parameters were monitored weekly during dose escalation, week 6 and week 12.Results: Weight loss was 1.8 kg for placebo and 0.4 kg for 500 mg NT whereas the 250 mg bed- and freeze-dried NT gained 0.43 and 0.87 kg, respectively (P=NS). The food intake increased 74 kcal with 250 mg freeze-dried NT and decreased 193.7 kcal with 500 mg freeze-dried NT (P<0.01). There was a dose-related incidence of loose stools in the NT groups, but no other toxicity was seen. Number Ten was found to contain sennosides, known laxatives and gallic acid, which is known to give weight loss in rodents.Discussion: The human dose equivalent of NT used in this study was & frac16; and & frac112; of that shown to give well-tolerated weight loss in rodents. Number Ten will not be an effective dietary herbal supplement for the treatment of obesity owing to dose-limiting gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]

Objective:To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss.Design:Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels.Patients:A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30–65 kg/m2) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38±11 year), weight (110.7±23 kg), and BMI (39.8±6.5 kg/m2) were similar across the four treatment groups.Measurements:Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis – 3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Lite™); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events.Results:After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of −1.98 and −1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during the 6-month treatment in the two higher dose groups. The lowest dose to reach statistical significance in weight loss after 6 months' treatment was 40 mg. Post hoc analysis revealed a 3.5–3.8% weight loss at month 6 in the two higher dose groups among Caucasian patients having insulin secretion greater than the median of the cohort, defined as CIRgp (corrected insulin response at the glucose peak) 1.43. There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake. Mean changes of blood glucose AUC0–180 min during an oral glucose tolerance test in patients taking octreotide LAR were 39–40 mg/dl h higher than those on placebo. A total of 7–21% of the patients taking octreotide LAR reached a 5% or greater decrease in body weight from Baseline, compared to 11% for the placebo group. This was not statistically significant. The most common adverse events included diarrhea, headache, cholelithiasis, nausea, and abdominal pain.Conclusion:Octreotide LAR given at 40 or 60 mg resulted in statistically significant weight loss. A post hoc analysis stratifying patients by race and CIRgp indicated that Caucasian patients with the greater degree of insulin hypersecretion appeared to derive the most benefit from treatment. The observed safety profile was consistent with the known effects of octreotide from previous studies.International Journal of Obesity (2006) 30, 331–341. doi:10.1038/sj.ijo.0803074; published online 13 September 2005 [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study investigated whether baseline eating behavior, emotions, and body image were significant predictors of change in body mass index (BMI) over 6 month and 12 month time intervals for individuals enrolled in a weight loss program that combined appetite suppressant medications and behavior therapy for obesity. METHOD: Participants were asked to complete self-report questionnaires at baseline, 6 months, and 12 months. In addition, their height and weight were measured and they were administered a body image assessment procedure at each time interval. RESULTS: At baseline, perceived hunger, dietary restraint, current body size, and trait anxiety were important components in a model for prediction of weight loss at 6 months. Perceived hunger, dietary restraint, and current body size as measured at baseline were important components in the prediction of weight loss at 12 months. These predictive variables, together with gender and initial BMI, accounted for 48.6% of the variance in weight loss at 6 months and 51.7% of the variance in weight loss at 12 months. DISCUSSION: These findings suggest that scores on certain paper and pencil tests may be useful as predictors of success or failure for individuals entering a weight loss program using pharmacological and behavioral interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: A new measure of body image, named the body image assessment for obesity (BIA-O) was developed and tested for reliability and validity in a sample of 1209 adult men and women. Separate BIA-O procedures were developed for men and women. Current, ideal and reasonable body image estimates of Caucasian and African-American men and women were compared. METHOD: Figural stimuli of males and females were developed for body sizes ranging from very thin to very obese in 18 increments. Participants selected figures that represented estimates of current, ideal and reasonable (a body size that could be maintained over time) body size. Some participants (n=641) also completed two measures of body dissatisfaction in a test of the validity of the BIA-O as a measure of body dissatisfaction. A sample of 77 participants was administered the BIA-O on two occasions to test the test–retest reliability of the BIA-O. RESULTS: The reliability of the BIA-O was supported by test–retest reliability coefficients which ranged from 0.65 to 0.93. Concurrent validity of the discrepancy between current and ideal and current and reasonable body size estimates was supported by positive correlations with two measures of body dissatisfaction. The BIA-O body size estimates of Caucasians and African-Americans, controlled for age and BMI, were compared. As BMI increased, Caucasian men and women were found to select larger current body size estimates in comparison to African-Americans. DISCUSSION: The reliability and validity of the BIA-O were supported. Greater body size dissatisfaction in obese Caucasians, relative to African-Americans of the same size, may be a function of biased estimates of current body size. International Journal of Obesity (2000) 24, 1326–1332 [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the relationship between two common apoA-IV variants (Thr347→Ser; Gln360→His), and body mass index (BMI) and percentage body fat. DESIGN: Cross-sectional study. SUBJECTS: Eight-hundred and forty-eight subjects screened for participation in ongoing clinical studies. MEASUREMENTS: ApoA-IV genotype, body mass index, waist-to-hip ratio and percentage body fat by bioelectric impedance. RESULTS: Participants had an average age of 41±12 y and an average BMI of 28.2±5.5 kg/m2. Individuals homozygous for the Ser347 allele had higher BMI (32.3±6.6 vs 28.6±5.3 kg/m2; P<0.01) and percentage body fat (36.9±7.8 vs 31.0±9.6%; P<0.05) compared with individuals homozygous for Thr347. In contrast, the presence of at least one copy of the His360 allele was associated with lower BMI (27.2±5.0 vs 28.4±5.6 kg/m2; P<0.05) and percentage body fat (28.6±8.2 vs 30.7±9.1%; P<0.05). The genotype effects persisted after normalization of the data for the potential confounding effects of gender, age and race. When grouped by BMI percentile, the frequency of the Ser347/Ser347 genotype increased while the frequency of the His360 allele decreased with increasing BMI. CONCLUSIONS: These data suggest a role for apoA-IV in fat storage or mobilization and that genetic variations in the apoA-IV gene may play a role in the development of obesity. International Journal of Obesity (2000) 24, 945–953 [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study compared fat oxidation rates during an acute bout of cycle ergometry exercise (E) typical of progressive fat oxidation in healthy, but sedentary, women of different obesity histories. DESIGN: Five never-obese (NO) (mean age=25±3 (s.e.)y, mean body fat=25.0±2.8 (s.e.)%), five obese (O) (26±3 y, 44.4±1.7%), and five post-obese (PO) (22±1 y, 32.2±3.0%) women cycled for 60 min at 60-65% peak VO[sub 2]. To identify the specific effects of E, a control trial consisting of 60 min of seated rest (R) was also performed. E and R trials were counterbalanced one month apart in the follicular phase and conducted following a 3 d normalized, eucaloric diet. MEASUREMENTS: Dual energy X-ray absorptiometry (DEXA) was used to determine body composition, and all were weight stable for at least eight weeks prior to experimentation. During both trials breath by breath measurements of VO[sub 2] and RER were used to determine substrate oxidation and energy expenditure. Blood samples were collected for hormone and metabolite analysis before, and every 15 min during exercise or rest. RESULTS: All three groups showed a similar and progressive shift toward fat oxidation as exercise progressed. No group differences were observed for E energy expenditure or fat oxidation. Glycerol (P<0.0001) and free fatty acids (P<0.0001) increased similarly in all three groups, but PO maintained the highest free fatty acid level during exercise (group effect; P<0.01). E and R decreased (P<0.001 for both) insulin levels across groups, with lowest levels noted in PO and highest in O. Plasma epinephrine (P<0.0001) and norepinephrine (P<0.001) increased similarly during E in all three groups. Plasma growth hormone (GH) levels rose (P<0.05) during E, with a pronounced increase observed in PO. CONCLUSION: We conclude that exercise of equal relative intensity elicited similar fat oxidation rates among NO, O, and PO women, despite group differences... [ABSTRACT FROM AUTHOR]