Effect of chronic consumption of almonds on body weight in healthy humans

Small changes of diet may reduce CVD risk. One example is the inclusion of nuts. They are rich in fibre, unsaturated fatty acids and phytonutrients. However, their fat content and energy density raise concerns that chronic consumption will promote weight gain. Randomised intervention studies are required to evaluate whether this concern is well founded. This study's aim was to determine if the inclusion of a 1440 kJ serving of almonds in the daily diet results in positive energy balance, and body composition change. During a 23-week cross-over design study, participants were required to consume almonds for 10 weeks and were provided no advice on how to include them in their diet. For another 10 weeks (order counter-balanced), participants followed their customary diet and there was a 3-week washout between. The study group consisted of twenty women. Potential mechanisms of energy dissipation were measured. Ten weeks of daily almond consumption did not cause a change in body weight. This was predominantly due to compensation for the energy contained in the almonds through reduced food intake from other sources. Moreover, inefficiency in the absorption of energy from almonds was documented (P <0·05). No changes in resting metabolic rate, thermic effect of food or total energy expenditure were noted. A daily 1440 kJ serving of almonds, sufficient to provide beneficial effects on cardiovascular risk factors, may be included in the diet with limited risk of weight gain. Whether this can be generalised to other high-fat energy dense foods warrants evaluation.

Extravascular lung water indexed to predicted body weight is a novel predictor of intensive care unit mortality in patients with acute lung injury

Objectives: Acute lung injury and the acute respiratory distress syndrome are characterized by noncardiogenic pulmonary edema, which can be assessed by measurement of extravascular lung water. Traditionally, extravascular lung water has been indexed to actual body weight (mL/kg). Because lung size is dependent on height rather than weight, we hypothesized indexing to predicted body weight may be a better predictor of mortality in acute lung injury/acute respiratory distress syndrome.

Chronic treatment with a stable obestatin analogue significantly alters plasma triglyceride levels but fails to influence food intake, fluid intake, body weight, or body composition in rats.

Obestatin (OB(1-23) is a 23 amino acid peptide encoded on the preproghrelin gene, originally reported to have metabolic actions related to food intake, gastric emptying and body weight. The biological instability of OB(1-23) has recently been highlighted by studies demonstrating its rapid enzymatic cleavage in a number of biological matrices. We assessed the stability of both OB(1-23) and an N-terminally PEGylated analogue (PEG-OB(1-23)) before conducting chronic in vivo studies. Peptides were incubated in rat liver homogenate and degradation monitored by LC-MS. PEG-OB(1-23) was approximately 3-times more stable than OB(1-23). Following a 14 day infusion of Sprague Dawley rats with 50 mol/kg/day of OB(1-23) or a N-terminally PEGylated analogue (PEG-OB(1-23)), we found no changes in food/fluid intake, body weight and plasma glucose or cholesterol between groups. Furthermore, morphometric liver, muscle and white adipose tissue (WAT) weights and tissue triglyceride concentrations remained unaltered between groups. However, with stabilised PEG-OB(1-23) we observed a 40% reduction in plasma triglycerides. These findings indicate that PEG-OB(1-23) is an OB(1-23) analogue with significantly enhanced stability and suggest that obestatin could play a role in modulating physiological lipid metabolism, although it does not appear to be involved in regulation of food/fluid intake, body weight or fat deposition.

Adiponectin multimers, body weight and markers of cardiovascular risk in adolescence: Northern Ireland Young Hearts Project:Northern Ireland Young Hearts Project

Background:Research examining the relationship between adiponectin (AN) isoforms, body weight and cardiovascular (CV) risk factors is limited, particularly in younger populations. Objectives:To investigate the inter-relationships between AN isoforms and CV risk factors, and their dependence on body weight status, in adolescents. Design:Blood samples from 92 obese, 92 overweight and 92 normal weight age- and sex-matched adolescents were analysed for traditional cardiovascular disease (CVD) risk biomarkers and also total, high molecular weight (HMW), medium and low molecular weight (LMW) AN. Results:A significant inverse association was observed between total and HMW AN and waist-hip ratio (P=0.015, P=0.006, respectively), triglycerides (P=0.003, P=0.003, respectively) and systolic blood pressure (P=0.012, P=0.024, respectively) and a significant positive association with high-density lipoprotein (P<0.001, P<0.001, respectively) in multi-adjusted analyses. There was no evidence of a relationship between multimeric AN and high-sensitivity C-reactive protein. There was also little evidence of a relationship between LMW AN and CVD risk factors. There was a strong, body mass index (BMI)-independent, association between AN, CVD biomarkers and the hypertriglyceridemic waist phenotype. Conclusion:Prominent, BMI-independent associations between total and HMW AN, but not LMW AN, and CVD risk factors were already evident in this young population. This research in adolescents supports the contention that AN subfractions may have different biological actions. These associations in apparently healthy adolescents suggest an important role for AN and its subfractions in the pathogenesis of metabolic syndrome traits and indicate that the potential for total or HMW AN to act as early universal biomarkers of CV risk warrants further study.

Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome

To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome.

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice

Background and purpose: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action.

Experimental approach: Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes.

Key results: Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, galegine (50 µm-3 mm) stimulated glucose uptake. Galegine (1–300 µm) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 µm) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 µm and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes.

Conclusions and implications: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

Body size differs in workers produced across time and is associated with variation in the quantity and composition of larval food in Nannotrigona perilampoides (Hymenoptera, Meliponini)

Although variation in body size has been recently reported in stingless bees (Meliponini), empirical evidence evaluating possible factors related to such variation is lacking, and thus it is not clear if it may have an adaptive significance. We evaluated if variation in the body size and weight of workers of stingless bees fluctuates across a seasonal pattern and if this could be related to characteristics of the food consumed during the larval stage. The weight of larval provisions, their protein, and sugar content were evaluated in four colonies of Nannotrigona perilampoides every 2 months across 1 year. Worker-destined larvae from the same combs were allowed to develop and were sampled as callow workers to determine their weight and size using morphometric data. The weight and size of workers were highly correlated and varied across the seasons in established colonies, suggesting that size variation cycles across the year in stingless bees. An increase in the protein content and, to a lesser degree, the quantity of larval food were positively linked to variation in body weight and size; food with richer protein content resulted in larger and heavier workers. This study provides the first evidence of an effect of the quantity and composition of larval food on the size of workers in stingless bees. Although body weight and size of workers differed across seasons, they were not readily noticeable as changes seem to occur as a continuum across the year. Since size polymorphism was of a larger magnitude across time but not within age cohorts and as it was highly determined by food resources, it may not be an adaptive feature in stingless bees. However, more studies are needed to determine the role of the cyclical change in worker body size on colony performance and thus its adaptive significance in stingless bees.

Effect of a Web-Based Behavior Change Program on Weight Loss and Cardiovascular Risk Factors in Overweight and Obese Adults at High Risk of Developing Cardiovascular Disease:Randomized Controlled Trial

BACKGROUND: Web-based programs are a potential medium for supporting weight loss because of their accessibility and wide reach. Research is warranted to determine the shorter- and longer-term effects of these programs in relation to weight loss and other health outcomes.

OBJECTIVE: The aim was to evaluate the effects of a Web-based component of a weight loss service (Imperative Health) in an overweight/obese population at risk of cardiovascular disease (CVD) using a randomized controlled design and a true control group.

METHODS: A total of 65 overweight/obese adults at high risk of CVD were randomly allocated to 1 of 2 groups. Group 1 (n=32) was provided with the Web-based program, which supported positive dietary and physical activity changes and assisted in managing weight. Group 2 continued with their usual self-care (n=33). Assessments were conducted face-to-face. The primary outcome was between-group change in weight at 3 months. Secondary outcomes included between-group change in anthropometric measurements, blood pressure, lipid measurements, physical activity, and energy intake at 3, 6, and 12 months. Interviews were conducted to explore participants' views of the Web-based program.

RESULTS: Retention rates for the intervention and control groups at 3 months were 78% (25/32) vs 97% (32/33), at 6 months were 66% (21/32) vs 94% (31/33), and at 12 months were 53% (17/32) vs 88% (29/33). Intention-to-treat analysis, using baseline observation carried forward imputation method, revealed that the intervention group lost more weight relative to the control group at 3 months (mean -3.41, 95% CI -4.70 to -2.13 kg vs mean -0.52, 95% CI -1.55 to 0.52 kg, P<.001), at 6 months (mean -3.47, 95% CI -4.95 to -1.98 kg vs mean -0.81, 95% CI -2.23 to 0.61 kg, P=.02), but not at 12 months (mean -2.38, 95% CI -3.48 to -0.97 kg vs mean -1.80, 95% CI -3.15 to -0.44 kg, P=.77). More intervention group participants lost ≥5% of their baseline body weight at 3 months (34%, 11/32 vs 3%, 1/33, P<.001) and 6 months (41%, 13/32 vs 18%, 6/33, P=.047), but not at 12 months (22%, 7/32 vs 21%, 7/33, P=.95) versus control group. The intervention group showed improvements in total cholesterol, triglycerides, and adopted more positive dietary and physical activity behaviors for up to 3 months verus control; however, these improvements were not sustained.

CONCLUSIONS: Although the intervention group had high attrition levels, this study provides evidence that this Web-based program can be used to initiate clinically relevant weight loss and lower CVD risk up to 3-6 months based on the proportion of intervention group participants losing ≥5% of their body weight versus control group. It also highlights a need for augmenting Web-based programs with further interventions, such as in-person support to enhance engagement and maintain these changes.

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10(-5), Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10(-06)/Pfemales: 3.45 × 10(-07)/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation.

The £ for lb challenge – a lose – win – win scenario. Results from a novel workplace-based, peer-led weight management programme

Title: The £ for lb. Challenge – A lose - win – win scenario. Results from a novel workplace-based, peer-led weight management programme in 2016.

Names: Damien Bennett, Declan Bradley, Angela McComb, Amy Kiernan, Tracey Owen

Background: Tackling obesity is a public health priority. The £ for lb. Challenge is the first country wide, workplace-based peer-led weight management programme in the UK or Ireland with participants from a range of private and public businesses in Northern Ireland (NI).
Intervention: The intervention was workplace-based, led by workplace Champions and based on the NHS Choices 12 week weight loss guide. It operated from January to April 2016. Overweight and obese adult workers were eligible. Training of Peer Champions (staff volunteers) involved two half day workshops delivered by dieticians and physical activity professionals.
Outcome measurement: Weight was measured at enrolment and 12 weekly intervals. Changes in weight, % weight, BMI and % BMI were determined for the whole cohort and sex and deprivation subgroups.
Results: There were 1513 eligible participants from 35 companies. Engagement rate was 98%. 75% of participants completed the programme. Mean weight loss was 2.4 kg or 2.7%. Almost a quarter (24%) lost at least 5% initial bodyweight. Male participants were over twice as likely to complete the programme and three times more likely to lose 5% body weight or more. Over £17,000 was raised for NI charities.
Discussion: The £ for lb. Challenge is a successful health improvement programme with important weight loss for many participants, particularly male workers. With high levels of user engagement and ownership and successful multidisciplinary collaboration between public health, voluntary bodies, private and public companies it is a novel workplace based model with potential to expand.

Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide

Glucose dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with therapeutic potential for type 2 diabetes due to its insulin-releasing and antihyperglycaemic actions. However, development of GIP-based therapies is limited by N-terminal degradation by DPP IV resulting in a very short circulating half-life. Numerous GIP analogues have now been generated exhibiting DPP IV resistance and extended bioactivity profiles. In this study, we report a direct comparison of the long-term antidiabetic actions of three such GIP molecules, N-AcGIP, GIP(LyS(37)PAL) and N-AcGIP(LyS(37)PAL) in obese diabetic (ob/ob) mice. An extended duration of action of each GIP analogue was demonstrated prior to examining the effects of once daily injections (25 nmol kg(-1) body weight) over a 14-day period. Administration of either N-AcGIP, GIP(LyS(37)PAL) or N-AcGIP(LyS37PAL) significantly decreased non-fasting plasma glucose and improved glucose tolerance compared to saline treated controls. All three analogues significantly enhanced glucose and nutrient-induced insulin release, and improved insulin sensitivity. The metabolic and insulin secretory responses to native GIP were also enhanced in 14-day analogue treated mice, revealing no evidence of GIP-receptor desensitization. These effects were accompanied by significantly enhanced pancreatic insulin following N-AcGIP(Lys(37)PAL) and increased islet number and islet size in all three groups. Body weight, food intake and circulating glucagon were unchanged. These data demonstrate the therapeutic potential of once daily injection of enzyme resistant GIP analogues and indicate that N-AcGIP is equally as effective as related palmitate derivatised analogues of GIP. (c) 2006 Elsevier Inc. All rights reserved.

A novel, long-acting agonist of glucose-dependent insulinotropic polypeptide suitable for once-daily administration in type 2 diabetes

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with a potentially therapeutic role in type 2 diabetes. Rapid degradation by dipeptidylpeptidase IV has prompted the development of enzyme-resistant N-terminally modified analogs, but renal clearance still limits in vivo bioactivity. In this study, we report long-term antidiabetic effects of a novel, N-terminally protected, fatty acid-derivatized analog of GIP, N-AcGIP(LysPAL(37)), in obese diabetic (ob/ob) mice. Once-daily injections of N-AcGIP(LysPAL(37)) over a 14-day period significantly decreased plasma glucose, glycated hemoglobin, and improved glucose tolerance compared with ob/ob mice treated with saline or native GIP. Plasma insulin and pancreatic insulin content were significantly increased by N-AcGIP(LysPAL(37)). This was accompanied by a significant enhancement in the insulin response to glucose together with a notable improvement of insulin sensitivity. No evidence was found for GIP receptor desensitization and the metabolic effects of NAcGIP(LysPAL(37)) were independent of any change in feeding or body weight. Similar daily injections of native GIP did not affect any of the parameters measured. These data demonstrate the ability of once-daily injections of N-terminally modified, fatty acid-derivatized analogs of GIP, such as N-AcGIP(LysPAL(37)), to improve diabetes control and to offer a new class of agents for the treatment of type 2 diabetes.

Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice

Glucosedependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine Kcells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro(3))GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro(3))GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight. Nonfasting plasma glucose concentrations were significantly raised (p