Normal weight obesity: relationship with lipids, glycaemic status, liver enzymes and inflammation

BACKGROUND AND AIMS: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI) and has been associated with early inflammation, but its relationship with cardiovascular risk factors await investigation. METHODS AND RESULTS: Cross-sectional study including 3213 women and 2912 men aged 35-75 years to assess the clinical characteristics of NWO in Lausanne, Switzerland. Body fat was assessed by bioimpedance. NWO was defined as a BMI<25 kg/m(2) and a % body fat ≥66(th) gender-specific percentiles. The prevalence of NWO was 5.4% in women and less than 3% in men, so the analysis was restricted to women. NWO women had a higher % of body fat than overweight women. After adjusting for age, smoking, educational level, physical activity and alcohol consumption, NWO women had higher blood pressure and lipid levels and a higher prevalence of dyslipidaemia (odds-ratio=1.90 [1.34-2.68]) and fasting hyperglycaemia (odds-ratio=1.63 [1.10-2.42]) than lean women, whereas no differences were found between NWO and overweight women. Conversely, no differences were found between NWO and lean women regarding levels of CRP, adiponectin and liver markers (alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase). Using other definitions of NWO led to similar conclusions, albeit some differences were no longer significant. CONCLUSION: NWO is almost nonexistent in men. Women with NWO present with higher cardiovascular risk factors than lean women, while no differences were found for liver or inflammatory markers. Specific screening of NWO might be necessary in order to implement cardiovascular prevention.

New clinical practice guideline on enteral feeding in very low birth weight infants; first part.

The nutrition of very low birth weight (VLBW) infants is aimed at promoting a similar growth to that occurring in the uterus. However, in practice this is difficult to achieve and extrauterine growth restriction is frequent. The current tendency is to avoid this restriction by means of early parenteral and enteral nutrition. Nonetheless, uncertainty about many of the practices related with nutrition has resulted in a great variation in the way it is undertaken. In 2009 and 2011 in our hospital there was an unexpected increase in necrotizing enterocolitis. To check to see whether our nutrition policy was involved, we undertook a systematic review and drew up clinical practice guidelines (CPG) about enteral feeding in VLBW infants. New considerations about the duration of the fortification and the use of probiotics have led to an update of these CPG. METHODS: A total of 21 clinical questions were designed dealing with the type of milk, starting age, mode of administration, rate and volume of the increments, fortification, use of probiotics and protocol. After conducting a systematic search of the available evidence, the information was contrasted and summarized in order to draw up the recommendations. The quality of the evidence and the strength of the recommendations were determined from the SIGN scale. COMMENT: These CPG aim to help physicians in their decision making. The protocolized application of well-proven measurements reduces the variation in clinical practice and improves results.

Perturbation expansions of multilocus fixation probabilities for frequency-dependent selection with applications to the Hill-Robertson effect and to the joint evolution of helping and punishment.

Natural populations are of finite size and organisms carry multilocus genotypes. There are, nevertheless, few results on multilocus models when both random genetic drift and natural selection affect the evolutionary dynamics. In this paper we describe a formalism to calculate systematic perturbation expansions of moments of allelic states around neutrality in populations of constant size. This allows us to evaluate multilocus fixation probabilities (long-term limits of the moments) under arbitrary strength of selection and gene action. We show that such fixation probabilities can be expressed in terms of selection coefficients weighted by mean first passages times of ancestral gene lineages within a single ancestor. These passage times extend the coalescence times that weight selection coefficients in one-locus perturbation formulas for fixation probabilities. We then apply these results to investigate the Hill-Robertson effect and the coevolution of helping and punishment. Finally, we discuss limitations and strengths of the perturbation approach. In particular, it provides accurate approximations for fixation probabilities for weak selection regimes only (Ns < or = 1), but it provides generally good prediction for the direction of selection under frequency-dependent selection.

Plasma phospholipid long-chain n-3 polyunsaturated fatty acids and body weight change.

OBJECTIVE We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. METHOD A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. RESULTS The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. CONCLUSION The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.

Protocol for the modeling the epidemiologic transition study: a longitudinal observational study of energy balance and change in body weight, diabetes and cardiovascular disease risk.

ABSTRACT: BACKGROUND: The prevalence of obesity has increased in societies of all socio-cultural backgrounds. To date, guidelines set forward to prevent obesity have universally emphasized optimal levels of physical activity. However there are few empirical data to support the assertion that low levels of energy expenditure in activity is a causal factor in the current obesity epidemic are very limited. METHODS: The Modeling the Epidemiologic Transition Study (METS) is a cohort study designed to assess the association between physical activity levels and relative weight, weight gain and diabetes and cardiovascular disease risk in five population-based samples at different stages of economic development. Twenty-five hundred young adults, ages 25-45, were enrolled in the study; 500 from sites in Ghana, South Africa, Seychelles, Jamaica and the United States. At baseline, physical activity levels were assessed using accelerometry and a questionnaire in all participants and by doubly labeled water in a subsample of 75 per site. We assessed dietary intake using two separate 24-h recalls, body composition using bioelectrical impedance analysis, and health history, social and economic indicators by questionnaire. Blood pressure was measured and blood samples collected for measurement of lipids, glucose, insulin and adipokines. Full examination including physical activity using accelerometry, anthropometric data and fasting glucose will take place at 12 and 24 months. The distribution of the main variables and the associations between physical activity, independent of energy intake, glucose metabolism and anthropometric measures will be assessed using cross-section and longitudinal analysis within and between sites. DISCUSSION: METS will provide insight on the relative contribution of physical activity and diet to excess weight, age-related weight gain and incident glucose impairment in five populations' samples of young adults at different stages of economic development. These data should be useful for the development of empirically-based public health policy aimed at the prevention of obesity and associated chronic diseases.

Population pharmacokinetics of teicoplanin in children.

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment (Kcp), 0.474/3.876 h(-1) (8.16 h(-1)); and first-order rate constant from peripheral to central compartment (Kpc), 0.292/3.994 h(-1) (8.93 h(-1)). The percentage of patients with a minimum concentration of drug in serum (Cmin) of <10 mg/liter was 53.85%. The median/mean (SD) total population area under the concentration-time curve (AUC) was 619/527.05 mg · h/liter (166.03 mg · h/liter). Based on Monte Carlo simulations, only 30.04% (median AUC, 507.04 mg · h/liter), 44.88% (494.1 mg · h/liter), and 60.54% (452.03 mg · h/liter) of patients weighing 50, 25, and 10 kg, respectively, attained trough concentrations of >10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.).

Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development.

Sirt3 is a mitochondrial NAD(+)-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout (LDLR(-/-)) and LDLR/Sirt3 double-knockout (Sirt3(-/-)LDLR(-/-)) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3-deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic core diameter). Likewise, plaque macrophage and T cell infiltration as well as endothelial activation remained unaltered. Electron microscopy of aortic walls revealed no difference in mitochondrial microarchitecture between both groups. Interestingly, loss of Sirt3 was associated with accelerated weight gain and an impaired capacity to cope with rapid changes in nutrient supply as assessed by indirect calorimetry. Serum lipid levels and glucose tolerance were unaffected by Sirt3 deletion in LDLR(-/-) mice. Sirt3 deficiency does not affect atherosclerosis in LDLR(-/-) mice. However, Sirt3 controls systemic levels of oxidative stress, limits expedited weight gain, and allows rapid metabolic adaptation. Thus, Sirt3 may contribute to postponing cardiovascular risk factor development.

Energy expenditure in obese women before and during weight loss, after refeeding, and in the weight-relapse period.

In 10 moderately obese women, 24-h energy expenditure (24EE) was measured in a respiration chamber under four conditions: 1) before weight loss (body weight = 77.9 kg), 2) during weight loss (63.9 kg), 3) after realimentation (62.5 kg), and 4) 6-15 mo after the study diet with ad libitum diet (67.7 kg). The 14 +/- 8 kg (mean +/- SD) weight loss produced a decrease in 24EE of 1498 +/- 1138 kJ/d (P < 0.001), ie, a decrease of weight of 107 kJ.kg body wt-1.d-1. The subsequent 24EE (conditions 3 and 4) remained lower than the value before weight loss. A significant correlation was found between changes before and after weight regain in basal respiratory quotient (RQ) and the spontaneous rate of body-weight gain after cessation of the period of low energy intake (r = 0.89, P < 0.01); this suggests that the value of the postabsorptive RQ may be a predictor of relapse of weight gain. After discontinuation of the low energy diet, an elevated postabsorptive RQ shows that the endogenous lipid oxidation is low, a condition favoring weight gain.