Iain Broom

Effects of Se‐depletion on glutathione peroxidase and selenoprotein W gene expression in the colon

Selenium (Se)‐containing proteins have important roles in protecting cells from oxidative damage. This work investigated the effects of Se‐depletion on the expression of the genes encoding selenoproteins in colonic mucosa from rats fed diets of different Se content and in human intestinal Caco‐2 cells grown in Se‐adequate or Se‐depleted culture medium. Se‐depletion produced statistically significant (P < 0.05) falls in glutathione peroxidase (GPX) 1 mRNA (60–83%) and selenoprotein W mRNA (73%) levels, a small but significant fall in GPX4 mRNA (17–25%) but no significant change in GPX2. The data show that SelW expression in the colon is highly sensitive to Se‐depletion.

Effect of weight loss on adipokine levels in obese patients

Background: Adipose tissue functions as an endocrine organ by releasing adipokines which have important roles in the regulation of inflammation and insulin sensitivity. Although there is evidence of improvement in circulating levels of adipokines with weight loss, few studies relate such changes to specific diets. We investigated the effects of weight loss achieved by two different diets on circulating adipokine levels in obese individuals. Methods: A total of 120 obese patients (body mass index ≥ 35 kg/m2) underwent a three-month screening period on a low-fat, reduced-calorie diet. Patients failing to achieve a 5% weight loss using this approach were randomly allocated to either a low carbohydrate/high protein diet (n = 17) or to a commercial very low calorie diet (LighterLife®, n = 14) for a period of nine months. Results: At nine months, a significant weight loss was only maintained for Lighter-Life® (−32.3 ± 22.7 kg, P < 0.0001) but not on the low carbohydrate/high protein diet. Changes in adiponectin (15.8 ± 17.1 ng/mL versus −0.8 ± 6.2 ng/mL, P = 0.003) and leptin (−17.6 ± 24.3 ng/mL versus −3.0 ± 9.2 ng/mL, P = 0.049) at nine months were significantly greater for LighterLife® than for the low carbohydrate/high protein diet, which may reflect greater weight loss and decrease in fat mass. Changes in tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor type 1 did not differ significantly between the dietary interventions at nine months. Conclusion: A significant weight loss of 23.8% from baseline weight was observed using a very low calorie diet and resulted in significant improvements in circulating levels of leptin, plasminogen activator inhibitor type 1, and adiponectin, which are likely to be due to weight loss and not macronutrient intake.

Randomized clinical trial of standard dietary treatment versus a low-carbohydrate ⁄high-protein diet or the LighterLife Programme in the management of obesity*

Background:  With the current obesity epidemic, the search for effective weight loss approaches is required. In the present study, changes in weight, body composition and cardiovascular (CV) risk in response to a low‐fat, reduced‐energy diet (LFRE), a low‐carbohydrate/high‐protein diet (LCHP), or a commercially available very low‐calorie diet (LighterLife; LL) were assessed.

Optimizing acceptability and feasibility of an evidence-based behavioral intervention for obese adults with obesity-related co-morbidities or additional risk factors for co-morbidities: An open-pilot intervention study in secondary care

OBJECTIVE To test and optimize the feasibility and acceptability of a physical activity (PA) and healthy eating behavior change intervention for obese adults with obesity-related co-morbidities or additional risk factors for co-morbidities. METHODS Open-pilot intervention study using an uncontrolled pre and post design with ongoing measures on intervention acceptability and feasibility. Participants received 5 weekly nurse-led one-hour long group sessions. Acceptability and feasibility were assessed throughout. PA, dietary behavior and weight were measured before and after the intervention. RESULTS Of 74 consenting participants, 61 (82%) received and 47 (64%) completed the intervention. Average ratings of intervention materials and components by participants ranged between 4.1 and 4.9 out of 5. Average facilitator satisfaction rating was 90% (range 75-100%). The intervention delivery was feasible as indicated by ratings and comments from participants and the facilitator. Participants lost -0.86 kg of weight t(45)=3.84, p=0.0001, and increased PA by an additional 1.6 (SD=2.7) sessions/week, t(31)=-3.3, p=0.002. No significant dietary differences emerged. CONCLUSION The intervention was acceptable to the facilitator and participants and feasible for delivery. Several intervention aspects were further optimized. PRACTICE IMPLICATIONS The current study outlines a PA and dietary behavior change pilot intervention coupled with a systematic and transparent process of intervention optimization.

The molecular contribution of TNF-α in the link between obesity and breast cancer

Obesity is a growing worldwide medical problem, as it pre-disposes the affected hosts to a number of severe diseases, including postmenopausal breast cancer. Obesity development is characterised, amongst others, by aberrant secretion of adipokines. White fat tissue infiltrating macrophages secrete tumour necrosis factor-α (TNF-α) so that its circulating levels correlate positively with body mass index (BMI). In the study presented here, the effect of TNF-α on cell proliferation, cell signalling pathway activation and cell cycle in two breast cancer cell lines and one breast epithelial cell lines was assessed to determine the contribution of TNF-α on breast cancer progression and aetiology, respectively. TNF-α acted differently on all three cell lines. In MDA-MB-231 breast cancer cells, cell proliferation and PI3-kinase activation were not affected, while MAP-kinase activation and cell cycle progression were decreased, with indications of increased apoptosis. This suggests a growth inhibitory function of TNF-α in these cells. In SK-BR-3 breast cancer cells, cell proliferation and cell signalling pathway activation increased, while cell cycle progression decreased, which contradictorily suggests both growth promoting and growth inhibiting properties of TNF-α on these cells. This makes TNF-α an unlikely candidate for a general contribution to the link between obesity and breast cancer progression, however, individual tumours may be responsive to a proliferative signal of TNF-α. In MCF-10A breast epithelial cells, cell proliferation and MAP-kinase activation increased, while cell cycle progression was unaffected. This suggests a strong proliferative response in these cells, suggesting the possibility that TNF-α may contribute to breast cancer aetiology as a novel link between obesity and increased risk of breast cancer development.

The Effects of Very-Low-Calorie Diets on HDL: A Review

This paper investigates the effects of very-low-calorie diets (VLCDs) used in the treatment of obesity on high-density lipoprotein (HDL) levels. Although the studies varied widely in their intervention format, duration, and baseline HDL levels, it would appear that HDL levels usually decrease during active weight loss using a VLCD, but these either return to pre-VLCD levels or improve overall during the weight-maintenance phase. More research needs to be done to determine optimal weight-maintenance programmes and the effects of VLCDs in the short term as well as on HDL levels in groups at increased risk of coronary heart disease.

The influence of birth weight and genetic factors on lipid levels : a study in adult twins

Twins can be used to investigate the biological basis for observed associations between birth weight and later disease risk, as they experience in utero growth restriction compared with singletons, which can differ in magnitude within twin pairs despite partial or total genetic identity. In the present study, sixty monozygotic and seventy-one dizygotic same-sex twin pairs aged 19-50 years and eighty-nine singleton controls matched for age, gestational age, sex, maternal age and parity were recruited from an obstetric database. Associations between fasting lipid levels and birth weight were assessed by linear regression with adjustment for possible confounding factors. Twins were significantly lighter at birth but were not significantly different in adult height, weight or lipid levels from the singleton controls. There was a significant inverse association between birth weight and both total and LDL-cholesterol levels among singleton controls (-0.53 mmol/l per kg (95 % CI -0.97, -0.09), P = 0.02 and -0.39 mmol/l per kg (95 % CI -0.76, -0.02), P = 0.04, respectively), but there was no significant association between birth weight and lipid levels in either unpaired or within-pair analysis of twins. The results suggest that the in utero growth restriction and early catch-up growth experienced by twins does not increase the risk of an atherogenic lipid profile in adult life.

Weight loss for individuals with type 2 diabetes following a very-low-calorie diet in a community-based setting with trained facilitators for 12 weeks

Approximately 80% of people with type 2 diabetes mellitus (T2DM) are overweight or obese. Weight loss produces numerous benefits in T2DM. People with T2DM have difficulty losing and maintaining weight.

Glucose uptake by the brain on chronic high-protein weight-loss diets with either moderate or low amounts of carbohydrate

Previous work has shown that hunger and food intake are lower in individuals on high-protein (HP) diets when combined with low carbohydrate (LC) intakes rather than with moderate carbohydrate (MC) intakes and where a more ketogenic state occurs. The aim of the present study was to investigate whether the difference between HPLC and HPMC diets was associated with changes in glucose and ketone body metabolism, particularly within key areas of the brain involved in appetite control. A total of twelve men, mean BMI 34·9 kg/m², took part in a randomised cross-over trial, with two 4-week periods when isoenergetic fixed-intake diets (8·3 MJ/d) were given, with 30% of the energy being given as protein and either (1) a very LC (22 g/d; HPLC) or (2) a MC (182 g/d; HPMC) intake. An ¹⁸fluoro-deoxyglucose positron emission tomography scan of the brain was conducted at the end of each dietary intervention period, following an overnight fast (n 4) or 4 h after consumption of a test meal (n 8). On the next day, whole-body ketone and glucose metabolism was quantified using [1,2,3,4-¹³C]acetoacetate, [2,4-¹³C]3-hydroxybutyrate and [6,6-²H₂]glucose. The composite hunger score was 14% lower (P= 0·013) for the HPLC dietary intervention than for the HPMC diet. Whole-body ketone flux was approximately 4-fold greater for the HPLC dietary intervention than for the HPMC diet (P< 0·001). The 9-fold difference in carbohydrate intakes between the HPLC and HPMC dietary interventions led to a 5% lower supply of glucose to the brain. Despite this, the uptake of glucose by the fifty-four regions of the brain analysed remained similar for the two dietary interventions. In conclusion, differences in the composite hunger score observed for the two dietary interventions are not associated with the use of alternative fuels by the brain.

Review: Thinking around abdominal obesity and cardiovascular risk

Obesity, particularly intra-abdominal (visceral) obesity, is a leading cause of cardiovascular disease (CVD), insulin resistance, type 2 diabetes, dyslipidaemia, inflammation and thrombosis. A useful indicator for visceral fat is waist circumference, which is associated with all-cause mortality. Pro-inflammatory adipokines play a causal role in the development of pathologies associated with insulin resistance, type 2 diabetes and CVD. In addition to established anti-obesity therapies, namely orlistat and sibutramine, a new type of agent that inhibits the cannabinoid receptor (CB1) is advanced in development to reduce appetite and act predominantly against intra-abdominal adiposity.