NPY5R antagonism does not augment the weight loss efficacy of orlistat or sibutramine

Objective: Central counter‐regulatory mechanisms, including those related to the orexigenic hormone neuropeptide Y (NPY), may limit the weight loss observed with conventional pharmacological monotherapy. This study evaluated whether blockade of the NPY Y5 receptor (NPY5R) with the selective antagonist MK‐0557 potentiates sibutramine and orlistat weight loss effects. Research Methods and Procedures: Obese patients (497, BMI 30 to 43 kg/m²) were randomized to 1 of 5 treatment arms [placebo, n = 101; sibutramine 10 mg/d, n = 100; MK‐0557 1 mg/d plus sibutramine 10 mg/d, n = 98; orlistat 120 mg TID, n = 99; MK‐0557 1 mg/d plus orlistat 120 mg TID, n = 99] in conjunction with a hypocaloric diet for 24 weeks. The all‐patients‐treated population, imputing missing data using last observation carried forward, was used to assess weight loss from baseline. Results: The study was completed by 71% of patients in placebo, 76% in sibutramine alone, 79% in MK‐0557 + sibutramine, 69% in orlistat alone, and 76% in MK‐0557 + orlistat groups. Least squares (LS) mean difference [95% confidence interval (CI)] in weight change from baseline between MK‐0557 + sibutramine and sibutramine alone was ?0.1 (?1.6, 1.4) kg (p = 0.892) and between MK‐0557 + orlistat and orlistat alone was ?0.9 (?2.4, 0.6) kg (p = 0.250). Sibutramine alone induced a LS mean weight loss of ?5.9 (?6.9, ?4.9) kg vs. ?4.6 (?5.7, ?3.6) kg for orlistat (p = 0.097). There were no serious drug‐related adverse events and MK‐0557 was well tolerated. Discussion: Blockade of the NPY5R with the potent antagonist MK‐0557 did not significantly increase the weight loss efficacy of either orlistat or sibutramine monotherapy.     

Prevalence and risk factors of overweight and obesity in China

Objective: To examine the prevalence and risk factors of overweight and obesity in China. Research Methods and Procedures: A cross‐sectional survey was conducted in a nationally representative sample of 15,540 Chinese adults in 2000–2001. Body weight, height, and waist circumference were measured by trained observers. Overweight and obesity were defined according to the World Health Organization classification. Central obesity was defined according to guidelines of the International Diabetes Federation. Results: Mean BMI and waist circumference were 23.1 kg/m² and 79.6 cm, respectively, for men and 23.5 kg/m² and 77.2 cm, respectively, for women. The prevalences of overweight and obesity were 24.1% and 2.8% in men and 26.1% and 5.0% in women, respectively. The prevalence of central obesity was 16.1% in men and 37.6% in women. The prevalences of overweight, obesity, and central obesity were higher among residents in northern China compared with their counterparts in southern China and among those in urban areas compared with those in rural areas. Lifestyle factors were the most important risk factors to explain the differences in overweight and central obesity between northern and southern residents. Among women, lifestyle and diet were the most important risk factors to explain the differences between urban and rural residents, whereas socioeconomic status, lifestyle, and diet were all important among men. Discussion: Our study indicates that overweight and obesity have become important public health problems in China. Environmental risk factors may be the main reason for regional differences in the prevalence of overweight and obesity in China.     

Waist circumference as a predictor of disability among older adults

Objective: Few studies have addressed the association between abdominal obesity, as measured by waist circumference (WC), and disability in the elderly. Moreover, those studies were cross‐sectional and yielded inconsistent results. The objective of this study was to examine longitudinally the association between WC and self‐reported disability among older adults. Research Methods and Procedures: A prospective cohort study was conducted from 2001 to 2003 in 3235 persons (1411 men and 1824 women) representative of the non‐institutionalized Spanish population ages 60 years and older. Baseline information was collected by home‐based personal interviews and measurement of WC, weight, and height. Two years later, information on disability was obtained by telephone interview. The association of interest was summarized with odds ratios obtained by logistic regression. Results: Among persons reporting no disability at baseline, WC predicted disability 2 years later. After adjustment for age, education, tobacco use, alcohol consumption, and physical activity, men in the highest WC quintile had 2.17 (95% confidence interval, 1.15 to 4.09) times more risk of mobility disability and 4.77 (95% confidence interval, 2.50 to 9.13) times more risk of agility disability than those in the lowest quintile. Additional adjustment for BMI, chronic diseases, and cognitive function led to only a slight reduction in this association. Results were similar for women. No statistically significant association was observed between WC and restriction of daily activities, limitation in instrumental activities of daily living, and limitation in bathing or dressing, in either men or women. Discussion: WC predicts mobility and agility disability in old age. Avoidance of the highest values of WC might decrease the risk of disability in older adults.     

Short sleep duration is associated with reduced leptin levels and increased adiposity: Results from the Quebec family study

Objective: To explore cross‐sectional associations between short sleep duration and variations in body fat indices and leptin levels during adulthood in a sample of men and women involved in the Québec Family Study. Research Methods and Procedures: Anthropometric measurements, plasma lipid‐lipoprotein profile, plasma leptin concentrations, and total sleep duration were determined in a sample of 323 men and 417 women ages 21 to 64 years. Results: When compared with adults reporting 7 to 8 hours of sleep per day, the adjusted odds ratio for overweight/obesity was 1.38 (95% confidence interval, 0.89 to 2.10) for those with 9 to 10 hours of sleep and 1.69 (95% confidence interval, 1.15 to 2.39) for those with 5 to 6 hours of sleep, after adjustment for age, sex, and physical activity level. In each sex, we observed lower adiposity indices in the 7‐ to 8‐hour sleeping group than in the 5‐ to 6‐hour sleeping group. However, all of these significant differences disappeared after statistical adjustment for plasma leptin levels. Finally, the well‐documented regression of plasma leptin levels over body fat mass was used to predict leptin levels of short‐duration sleepers (5 and 6 hours of sleep), which were then compared with their measured values. As expected, the measured leptin values were significantly lower than predicted values. Discussion: There may be optimal sleeping hours at which body weight regulation is facilitated. Indeed, short sleep duration predicts an increased risk of being overweight/obese in adults and is related to a reduced circulating leptin level relative to what is predicted by fat mass. Because sleep duration is a potentially modifiable risk factor, these findings might have important clinical implications for the prevention and treatment of obesity.     

Influence of knee osteoarthritis on exercise capacity and quality of life in obese adults

Objective: The objective was to determine whether knee osteoarthritis (OA) reduces exercise ambulatory capacity and impairs quality of life (QOL) in obese individuals. Research Methods and Procedures: There were 56 subjects, with and without knee OA, who were obese. The subjects were evaluated with anthropometric measurements, a body composition assessment, maximal cardiopulmonary exercise test, 6‐minute walk test (6‐MWT), perceived exertion (RPE), self‐reported disability [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)], and the Medical Outcomes Study Short Form 36 (SF‐36). Results: VO_2peak was significantly higher in the controls when compared with the patients (mean ± standard deviation, 1.584 ± 0.23 L/kg per min vs. 0.986 ± 0.20 L/kg per min; p < 0.001). Obese subjects without knee OA walked a significantly longer distance in the 6‐MWT than obese patients with knee OA (p < 0.001). We also observed significant negative correlation between Vo ₂max and RPE, WOMAC pain and physical limitation, and bodily pain and general health domains of short‐form 36. Discussion: Knee OA reduces exercise and ambulatory capacity and impairs QOL in obese individuals. RPE, WOMAC pain, and SF‐36 items might provide information about exercise capacity in the obese subjects with knee OA. Our study confirms that exercise capacity and QOL might be improved by energetic and intensive treatment of pain resulting from knee OA.     

Longitudinal patterns of breakfast eating in black and white adolescent girls

Objective: The objective was to describe the pattern of breakfast eating over time (“breakfast history”) and examine its associations with BMI and physical activity. Research Methods and Procedures: This longitudinal investigation of patterns of breakfast eating included 1210 black and 1161 white girls who participated in the 10‐year, longitudinal National Heart, Lung, and Blood Institute Growth and Health Study (NGHS). Three‐day food records were collected during annual visits beginning at ages 9 or 10 up to age 19. Linear regression and path analysis were used to estimate the associations between breakfast history, BMI, and physical activity. Results: Among girls with a high BMI at baseline, those who ate breakfast more often had lower BMI at the end of the study (age 19), compared with those who ate breakfast less often. Path analysis indicated that energy intake and physical activity mediated the association between patterns of breakfast eating over time and BMI in late adolescence. Discussion: The association between regular breakfast consumption over time and moderation of body weight among girls who began the study with relatively high BMI suggests that programs to address overweight in children and adolescents should emphasize the importance of physical activity and eating breakfast consistently.     

BMI and seatbelt use

Objective: Seatbelt use among obese persons may be reduced because seatbelts are uncomfortable. We investigated the association between obesity and seatbelt use with data from the 2002 Behavioral Risk Factor Surveillance System Survey. Research Methods and Procedures: Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs) for seatbelt use among overweight (BMI, 25.0 to 29.9), obese (BMI, 30.0 to 39.9), and extremely obese (BMI ≥ 40.0) persons, relative to a non‐overweight/non‐obese reference group (BMI ≤ 24.9), adjusted for age, race, gender, education, and state seatbelt law. Results: Adjusted odds ratios for seatbelt use were 0.89 (95% CI, 0.85 to 0.93) for overweight, 0.69 (0.66 to 0.73) for obese, and 0.45 (95% CI, 0.40 to 0.50) for extremely obese persons. Interaction effects were evident for all covariates, with stronger associations between increasing BMI and decreasing seatbelt use for women, increasing age, higher education, and residence in states with a secondary seatbelt law. There was a linear decrease in seatbelt use with increasing BMI for all subgroups except persons 18 to 24 years old. Discussion: Lack of seatbelt can be added to the list of risk factors associated with obesity. Effective preventive interventions are needed to promote seatbelt use among overweight and obese persons.     

The impact of confounders on the test performance of natriuretic peptides for cardiac dysfunction in subjects aged 80 and older

The hypothesis that natriuretic peptides could be used to identify ‘pancardiac’ damage has been proposed. However, multiple factors are known to influence circulating levels of natriuretic peptides, especially in the very old. Therefore, the impact of confounders on the association between natriuretic peptide levels and cardiac dysfunction was further explored in subjects aged 80 and older. A diagnostic cross-sectional study embedded within the BELFRAIL study (n = 567) was performed. Baseline BNP and NT-proBNP levels were measured and echocardiograms were performed at the subject's home. Cardiac dysfunction was defined as systolic dysfunction, valvular heart disease or isolated severe diastolic dysfunction. Several functional and structural echocardiographic parameters were independently related to circulating levels of natriuretic peptides. Cystatin C, BMI, β blockers, diabetes, heart frequency, usCRP, age and sex were identified as confounders. The prevalence of cardiac dysfunction was 17.1% in the subjects without and 30.8% in the subjects with chronic atrial fibrillation (CAF) or pacemaker (PM). Only in subjects with CAF or PM the C statistic for cardiac dysfunction improved after correcting for confounders. The post-test probability for a negative test (PTP−) ranged from 3.7% to 12.2% and the PTP+ ranged from 21.9% to 62.2% in different strata of confounders. According to these data adjusting for identified confounders does not improve the diagnostic accuracy of the natriuretic peptides for cardiac dysfunction, except in subjects with CAF or PM. Stratifying for individual confounders showed that different cut-off values could be used to optimize the diagnostic characteristics of natriuretic peptides.     

Oncoprotein BMI‐1 induces the malignant transformation of HaCaT cells

BMI‐1 (B‐cell‐specific Moloney murine leukemia virus integration site 1), a novel oncogene, has attracted much attention in recent years for its involvement in the initiation of a variety of tumors. Recent evidence showed that BMI‐1 was highly expressed in neoplastic skin lesions. However, whether dysregulated BMI‐1 expression is causal for the transformation of skin cells remains unknown. In this study, we stably expressed BMI‐1 in a human keratinocyte cell line, HaCaT. The expression of wild‐type BMI‐1 induced the malignant transformation of HaCaT cells in vitro. More importantly, we found that expression of BMI‐1 promoted formation of squamous cell carcinomas in vivo. Furthermore, we showed that BMI‐1 expression led to the downregulation of tumore suppressors, such as p16INK4a and p14ARF, cell adhesion molecules, such as E‐Cadherin, and differentiation related factor, such as KRT6. Therefore, our findings demonstrated that dysregulated BMI‐1 could indeed lead to keratinocytes transformation and tumorigenesis, potentially through promoting cell cycle progression and increasing cell mobility. J. Cell. Biochem. 106: 16–24, 2009. © 2008 Wiley‐Liss, Inc.     

A review on directional information in neural signals for brain-machine interfaces

Brain-machine interfaces (BMIs) can be characterized by the technique used to measure brain activity and by the way different brain signals are translated into commands that control an effector. We give an overview of different approaches and focus on a particular BMI approach: the movement of an artificial effector (e.g. arm prosthesis to the right) by those motor cortical signals that control the equivalent movement of a corresponding body part (e.g. arm movement to the right). This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single-units. Here, we review recent findings showing that analog neuronal population signals, ranging from intracortical local field potentials over epicortical ECoG to non-invasive EEG and MEG, can also be used to decode movement direction and continuous movement trajectories. Therefore, these signals might provide additional or alternative control for this BMI approach, with possible advantages due to reduced invasiveness.