Abstract: Consumption of long-chain n-3 PUFA, particularly DHA, has been shown to improve cardiovascular risk factors but the intake required to achieve benefits is unclear. We sought to determine the relationship between DHA intake, increases in erythrocyte DHA content and changes in blood lipids. A total of sixty-seven subjects (thirty-six male, thirty-one female, mean age 53 years) with fasting serum TAG > or = 1.1 mmol/l and BMI>25 kg/m(2) completed a 12-week, randomized, double-blind, placebo-controlled parallel intervention. Subjects consumed 2, 4 or 6 g/d of DHA-rich fish oil (26 % DHA, 6 % EPA) or a placebo (Sunola oil). Fasting blood lipid concentrations and fatty acid profiles in erythrocyte membranes were assessed at baseline and after 6 and 12 weeks. For every 1 g/d increase in DHA intake, there was a 23 % reduction in TAG (mean baseline concentration 1.9 (sem 0.1) mmol/l), 4.4 % increase in HDL-cholesterol and 7.1 % increase in LDL-cholesterol. Erythrocyte DHA content increased in proportion to the dose of DHA consumed (r 0.72, P < 0.001) and the increase after 12 weeks was linearly related to reductions in TAG (r - 0.38, P < 0.01) and increases in total cholesterol (r 0.39, P < 0.01), LDL-cholesterol (r 0.33, P < 0.01) and HDL-cholesterol (r 0.30, P = 0.02). The close association between incorporation of DHA in erythrocytes and its effects on serum lipids highlights the importance of erythrocyte DHA as an indicator of cardiovascular health status.

Abstract: Adolescence is a vulnerable period for the development of obesity, and adolescent weight tracks strongly into adulthood. Previous reviews of treatment strategies have failed to discriminate between adolescents and children, thereby, disregarding the uniqueness of this population. Hence, this review aims to summarise the evidence for treatment approaches for adolescent obesity. Pubmed, OVID, EBSCOhost and Google Scholar were searched for randomised controlled trials, meta-analyses and systematic reviews testing treatments for overweight/obese adolescents (aged 12-19 years), published from 1982-2006 in English. Eligible studies had to assess either weight, percentage overweight, body mass index (BMI) or body fat. Thirty-four randomised controlled trials were eligible. The results of this review indicate that the safety and efficacy of surgical and pharmacotherapy treatments for adolescent obesity is uncertain. Diet and physical activity approaches may improve obese status in the short term. However, obesity interventions appear more effective when strategies are combined, rather than when used in isolation. Psychological interventions, such as behavioural and cognitive behavioural therapy, show promise in achieving the necessary lifestyle changes for obesity reduction; however, long-term follow-up studies are needed. There were multiple limitations in appraising the literature. Inconsistent definitions of overweight/obesity make comparisons between studies difficult. Many studies have not used direct adiposity measures, have failed to assess pubertal status or have not used an exclusive adolescent sample. We conclude that, despite these limitations, current evidence indicates that behavioural and cognitive behavioural strategies combined with diet and physical activity approaches may assist in reducing adolescent obesity,although long-term follow-up studies are needed.

Abstract: BACKGROUND: Health claims link soy protein (SP) consumption, through plasma cholesterol reduction, to a decreased risk of heart disease. Soy isoflavones (ISOs), particularly in individuals who produce equol, might also contribute to lipid lowering and thus reduce SP requirements. OBJECTIVE: The objective was to examine the contributions of SP, ISOs, and equol to the hypocholesterolemic effects of soy foods. DESIGN: Nonsoy consumers (33 men, 58 women) with a plasma total cholesterol (TChol) concentration >5.5 mmol/L participated in a double-blind, placebo-controlled, crossover intervention trial. The subjects consumed 3 diets for 6 wk each in random order, which consisted of foods providing a daily dose of 1) 24 g SP and 70-80 mg ISOs (diet S); 2) 12 g SP, 12 g dairy protein (DP), and 70-80 mg ISOs (diet SD); and 3) 24 g DP without ISOs (diet D). Fasting plasma TChol, LDL cholesterol, HDL cholesterol, and triglycerides (TGs) were measured after each diet. RESULTS: TChol was 3% lower with the S diet (-0.17 +/- 0.06 mmol/L; P < 0.05) than with the D diet, and TGs were 4% lower with both the S (-0.14 +/- 0.05 mmol/L; P < 0.05) and SD (-0.12 +/- 0.05 mmol/L; P < 0.05) diets. There were no significant effects on LDL cholesterol, HDL cholesterol, or the TChol:HDL cholesterol ratio. On the basis of urinary ISOs, 30 subjects were equol producers. Lipids were not affected significantly by equol production. CONCLUSIONS: Regular consumption of foods providing 24 g SP/d from ISOs had no significant effect on plasma LDL cholesterol in mildly hypercholesterolemic subjects, regardless of equol-producing status.

Abstract: BACKGROUND: Cognitive behavioral therapy (CBT) teaches behavioral and cognitive strategies that focus on achieving and maintaining lifestyle changes. OBJECTIVE: We examined the effectiveness of a CBT program (CHOOSE HEALTH) for improving body composition, diet, and physical activity in overweight and obese adolescents. DESIGN: Adolescents [16 male, 31 female; aged 14.5 +/- 1.6 y; body mass index (BMI; in kg/m(2)) 30.9 +/- 4.2] were block-matched into 2 groups by age, sex, Tanner stage, BMI, and hip and waist circumferences and were randomly assigned to CBT or no treatment (control). CBT consisted of 10 weekly sessions, followed by 5 fortnightly telephone sessions. RESULTS: Compared with the control, over 20 wk, CBT improved (significant group x time interactions) BMI (CBT, -1.3 +/- 0.4; control, 0.3 +/- 0.3; P = 0.007), weight (CBT, -1.9 +/- 1.0 kg; control, 3.8 +/- 0.9 kg; P = 0.001), body fat (CBT, -1.5 +/- 0.9 kg; control, 2.3 +/- 1.0 kg; P = 0.001), and abdominal fat (CBT, -124.0 +/- 46.9 g; control, 50.1 +/- 53.5 g; P = 0.008). CBT showed a greater reduction in intake of sugared soft drinks as a percentage of total energy (CBT, -4.0 +/- 0.9%; control, -0.3 +/- 0.9%; P = 0.005 for group x time interaction), which was related to reductions in weight (r = 0.48, P = 0.04), BMI (r = 0.53, P = 0.02), and waist circumference (r = 0.54, P = 0.02). Physical activity did not change significantly. CONCLUSIONS: A 10-wk CBT program followed by 10 wk of fortnightly phone contact improved body composition in overweight and obese adolescents. Changes in soft drink consumption may have contributed to this benefit.

Abstract: OBJECTIVE: Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. DESIGN: Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2). RESULTS: A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05). CONCLUSION: Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.

Abstract: The long-chain (LC) n-3 PUFA content of pork, particularly DHA, can be increased by including 15 % PorcOmega(R) (a fortified tuna fishmeal product) in pig finisher diets. The aim of the present study was to see whether this enriched pork could deliver cardiovascular health benefits to consumers. In a double-blind intervention trial, thirty-three healthy adult volunteers (sixteen female and seventeen male) were randomised to consume either n-3-enriched or regular (control) pork (a selection of five fresh cuts totalling 1000 g/week) for 12 weeks. Fasting blood samples were collected every 4 weeks and analysed for serum lipids, maximally stimulated thromboxane production and erythrocyte fatty acid composition. The n-3-enriched pork provided subjects with 1.3 g LC n-3 PUFA per week. Erythrocyte DHA levels rose 15 % in the n-3 group and fell 5 % in the control group over 12 weeks (P = 0.001). Compared with the control group, serum TAG decreased to a greater extent in the n-3 group (P = 0.02) and serum thromboxane production increased to a lesser extent (P = 0.004). Changes in the latter were inversely associated with changes in incorporation of DHA into erythrocytes (r - 0.54; P < 0.05). Thus the modest increases in LC n-3 PUFA intake resulting from regular consumption of enriched pork can improve cardiovascular risk factors.

Abstract: LPL and its specific physiological activator, apolipoprotein C-II (apoC-II), regulate the hydrolysis of triglycerides (TGs) from circulating TG-rich lipoproteins. Previously, we developed a skeletal muscle-specific LPL transgenic mouse that had lower plasma TG levels. ApoC-II transgenic mice develop hypertriglyceridemia attributed to delayed clearance. To investigate whether overexpression of LPL could correct this apoC-II-induced hypertriglyceridemia, mice with overexpression of human apoC-II (CII) were cross-bred with mice with two levels of muscle-specific human LPL overexpression (LPL-L or LPL-H). Plasma TG levels were 319 +/- 39 mg/dl in CII mice and 39 +/- 5 mg/dl in wild-type mice. Compared with CII mice, apoC-II transgenic mice with the higher level of LPL overexpression (CIILPL-H) had a 50% reduction in plasma TG levels (P = 0.013). Heart LPL activity was reduced by approximately 30% in mice with the human apoC-II transgene, which accompanied a more modest 10% decrease in total LPL protein. Overexpression of human LPL in skeletal muscle resulted in dose-dependent reduction of plasma TGs in apoC-II transgenic mice. Along with plasma apoC-II concentrations, heart and skeletal muscle LPL activities were predictors of plasma TGs. These data suggest that mice with the human apoC-II transgene may have alterations in the expression/activity of endogenous LPL in the heart. Furthermore, the decrease of LPL activity in the heart, along with the inhibitory effects of excess apoC-II, may contribute to the hypertriglyceridemia observed in apoC-II transgenic mice.

Abstract: PURPOSE OF REVIEW: This review summarizes evidence for metabolic health benefits of tree nuts and groundnuts (peanuts). While a role for nuts in the dietary management of LDL-cholesterol is well established, it is evident that regular consumption of nuts may also help to counteract other cardiovascular and metabolic risk factors. RECENT FINDINGS: Nuts are not only energy dense foods, they are rich sources of monounsaturated and polyunsaturated fatty acids and other bioactive nutrients with important metabolic effects. Contrary to expectations, epidemiological studies indicate that regular consumption of nuts is unlikely to contribute to obesity or increased risk of diabetes. In fact, it may help to regulate body weight by suppressing appetite and fat absorption. Nut consumption counteracts dyslipidemia and has the capacity to improve circulatory function through the actions of multiple constituents (arginine, polyphenols) on endothelial mechanisms. SUMMARY: Nuts are densely packaged nutrients with wide-ranging cardiovascular and metabolic benefits, which can be readily incorporated in healthy diets. Their potential role in counteracting obesity and the metabolic syndrome warrants further investigation.

Abstract: OBJECTIVE: To identify an anatomically defined region of interest (ROI) from DXA assessment of body composition that when combined with anthropometry can be used to accurately predict intra-abdominal adipose tissue (IAAT) in overweight/obese individuals. RESEARCH METHODS AND PROCEDURES: Forty-one postmenopausal women (age, 49 to 66 years; BMI, 26 to 37 kg/m(2)) underwent anthropometric and body composition assessments. ROI were defined as quadrilateral boxes extending 5 or 10 cm above the iliac crest and laterally to the edges of the abdominal soft tissue. A single-slice computed tomography (CT) scan was measured at the L3 to L4 intervertebral space, and abdominal skinfolds were taken. RESULTS: Forward step-wise regression revealed the best predictor model of IAAT area measured by CT (r(2) = 0.68, standard error of estimate = 17%) to be: IAAT area (centimeters squared) = 51.844 + DXA 10-cm ROI (grams) (0.031) + abdominal skinfold (millimeters) (1.342). Interobserver reliability for fat mass (r = 0.994; coefficient of variation, 2.60%) and lean mass (r = 0.986, coefficient of variation, 2.67%) in the DXA 10-cm ROI was excellent. DISCUSSION: This study has identified a DXA ROI that can be reliably measured using prominent anatomical landmarks, in this case, the iliac crest. Using this ROI, combined with an abdominal skinfold measurement, we have derived an equation to predict IAAT in overweight/obese postmenopausal women. This approach offers a simpler, safer, and more cost-effective method than CT for assessing the efficacy of lifestyle interventions aimed at reducing IAAT. However, this warrants further investigation and validation with an independent cohort.

Abstract: OBJECTIVE: To evaluate metabolic effects of epigallocatechin gallate (EGCG) supplementation when combined with a program of regular aerobic exercise in overweight/obese post-menopausal women. METHODS: Thirty-eight overweight or obese postmenopausal women exercised at moderate intensity, viz. walking three times per week for 45 min at 75% of age-predicted maximum heart rate (HR), and took a 150 mg capsule of EGCG (Teavigo) or placebo (lactose) twice daily for 12 weeks. Blood parameters (lipids, glucose and insulin), blood pressure, heart rate, arterial function and anthropometry were assessed at 0, 6 and 12 wk. At wk 0 and 12, body composition was assessed by dual energy X-ray absorptiometry (DXA) and abdominal fat was assessed by DXA and computed tomography (CT). RESULTS: Waist circumference (p < 0.01), total body fat (p < 0.02), abdominal fat (by DXA) (p < 0.01) and intra abdominal adipose tissue (by CT) (p < 0.01) were reduced in both treatment groups, with no difference between placebo and Teavigo. Teavigo significantly decreased resting HR (p < 0.01) and reduced plasma glucose in subjects with impaired glucose tolerance (p < 0.05). CONCLUSIONS: Moderate consumption of EGCG can improve the health status of overweight individuals undergoing regular exercise by reducing HR and plasma glucose concentrations. Loss of body fat, however, may require a higher intake of EGCG, other catechins or addition of metabolic stimulants.

Abstract: Experimental T cell-mediated hepatitis induced by concanavalin A (ConA) results in the initiation of an inflammatory response and the production of cytokines. Adiponectin is an adipocytokine produced by adipose tissue that is involved in the reciprocal regulation of other cytokines, including tumor necrosis factor alpha (TNF-alpha). Concanavalin A administration to C57BL/6J mice reduced circulating levels of adiponectin, whereas leptin was markedly increased. Adiponectin messenger RNA expression in adipose tissue was also decreased; however, the expression of both the adiponectin receptors remained unchanged. Neutralization of TNF-alpha reduced ConA-induced liver damage, and this was associated with restored circulating levels of adiponectin. These findings indicate that inflammation-induced TNF-alpha is a critical mediator of adipose-tissue-derived adiponectin in vivo.

Abstract: Concanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNF alpha protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNF alpha was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNF alpha-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNF alpha-induced death.

Abstract: The increasing prevalence of overweight and obesity worldwide is daunting and requires prompt attention by the affected, health care profession, government and the pharmaceutical industry. Because overweight/obesity are defined as an excess of adipose tissue mass, all approaches in prevention and treatment must consider redirecting lipid storage in adipose tissue to oxidative metabolism. Lipid partitioning is a complex process that involves interaction between fat and other macronutrients, particularly carbohydrate. In an isocaloric environment, when fat is stored carbohydrate is oxidized and vice versa. Processes that influence fat partitioning in a manner in which weight is maintained must be modified by changes in organ-specific fat transport and metabolism. When therapy is considered, however, changes in lipid partitioning alone will be ineffective unless a negative energy balance is also achieved, i.e. energy expenditure exceeds energy intake. The intent of this review is to focus on molecules including hormones, enzymes, cytokines, membrane transport proteins, and transcription factors directly involved in fat trafficking and partitioning that could be potential drug targets. Some examples of favorably altering body composition by systemic and/or tissue specific modification of these molecules have already been provided with gene knockout and/or transgenic approaches in mice. The translation of this science to humans remains a challenging task.

Abstract: OBJECTIVE: Elevated tumour necrosis factor-alpha (TNF-alpha) production in adipose tissue has been associated with obesity. We investigated whether mononuclear cell production of TNF-alpha decreased with weight loss in an obese population. RESEARCH METHODS AND PROCEDURES: Seventeen obese patients with type 2 diabetes (BMI 32.5+/-0.9 kg/m(2)) and 33 obese, non-diabetic controls (BMI 31.2+/-0.5 kg/m(2)) underwent 12 weeks of 30% total energy restriction (6622+/-84 KJ per day). Every 4 weeks, weight and blood pressure were measured and fasting venous blood was analysed for lipid, glucose and insulin concentrations. At the beginning and end of energy restriction, mononuclear cells were isolated from whole blood and TNF-alpha production measured by ELSIA. RESULTS: TNF-alpha production was not associated with the degree of adiposity but was higher in diabetic subjects (P<0.04). There was a reduction after energy restriction (281+/-43 to 182+/-30 pg/ml, P<0.05) however the presence of type 2 diabetes did not influence the magnitude of this change. Plasma glucose and insulin levels decreased after weight loss in all subjects and weak correlations were found with TNF-alpha concentrations (r=0.3, P<0.05). CONCLUSIONS: We conclude that maximal production of TNF-alpha from mononuclear cells decreases with energy restriction and is weakly associated with plasma glucose and insulin concentrations in obese patients.

Abstract: We investigated whether a polymorphism in the promoter region of the TNFalpha gene (-308 A/G) is associated with reduced weight loss in obese Australian subjects on an energy restricted diet. 189 healthy subjects and 91 subjects with type II diabetes were genotyped for the -308 Nco I polymorphism using PCR-RFLP techniques. A subset of these subjects (211 females and 45 males), were placed on a 30% energy restricted diet (6200 kJ) for 12 weeks. Subjects were assessed every 2 weeks and changes in body weight, waist circumference and BMI were used as determinants of weight loss. Fasting plasma was analysed for glucose, insulin, lipids and free fatty acids. 64% of subjects were GG homozygotes, 31% were AG heterozygotes and 5% were AA homozygotes. There was no significant difference between the allele frequency in healthy subjects (0.21) and type 2 diabetic patients (0.24). The presence of the -308 A/G polymorphism did not significantly influence initial BMI, the amount of weight lost (GG, 8.1+/-0.65 kg, AG, 6.9+/-0.77 kg, AA, 7.6+/-0.12 kg), waist circumference or any metabolic variable. The AA variant at position -308 in the promoter region of the TNFalpha gene does not influence the amount of weight lost in overweight and obese men and women on a 30% energy restricted diet.

Abstract: We investigated in a clinical setting whether increased intake of linoleic acid alters respiratory function in 26 mild asthmatics. Subjects completed a 16-week-dietary intervention comprising 8 weeks eating an enriched n-6 polyunsaturated fat diet (9.2% energy from linoleic acid) and consuming either a high monounsaturated or saturated fat diet in a random cross-over resign for 8 weeks. Neither FEV1 nor PC20 values changed significantly after increased linoleic acid consumption when compared with the other diets. Increased consumption of linoleic acid caused a 20% rise (p < or = 0.01) in plasma linoleic acid, a 38% decrease (p < or = 0.01) in plasma eicosapentaenoic acid, but no change in arachidonic acid. There were no changes in symptom scores or bronchodilator use.

Abstract: Obesity is commonly associated with high rates of cardiovascular disease (CVD). Weight loss in obese subjects reduces risk factors for CVD but this response is not uniform. Genetic factors could be involved in this variability. The 360His polymorphism of apolipoproteinA-IV (apoA-IV) influences the lipid response to fat intake, but it is unclear whether this polymorphism could contribute to lipid variability during weight loss. Therefore, we assessed the effects of an energy restricted diet (6.3 MJ) for 12 weeks on weight loss and plasma lipids according to apoA-IV genotype in 186 overweight/obese subjects (BMI mean 33+/-4.3, range 25.0-48.0 kg/m(2)). The frequency of the 360His allele was 0.083. Energy restriction for 12 weeks resulted in an average weight loss of 8. 25+/-0.28 kg. HDL-C increased 5.4% in subjects with the apoA-IV-1/1 genotype with weight loss compared to a 2.6% decrease in apoA-IV-1/2 subjects (P=0.035). This was more apparent when only the subjects with type 2 diabetes (n=57) were analyzed (P=0.003). ApoA-IV genotype was not related to change in total cholesterol, LDL-C or triglyceride concentrations. Therefore, weight loss as a treatment to reduce CVD risk factors may be more effective in subjects with the apoA-IV-1/1 variant as compared to those with the apoA-IV-1/2 variant, especially in subjects with type 2 diabetes.

Abstract: AIMS/HYPOTHESIS: To determine whether genetic variation in uncoupling protein-1 (UCP-1) is associated with obesity or obesity-related risk factors in overweight women. METHODS: We genotyped 526 overweight/obese women (mean body mass index 34.1 kg/m2, range 25.0 to 47.5 kg/m2) for the -3826 A-->G uncoupling protein-1 polymorphism. Of the 526 women genotyped 144 had fasting blood samples analysed for glucose and lipid measurements. RESULTS: The -3826 G allele was found with a frequency of 0.23 and was associated with higher BMI (p = 0.02). A higher frequency of this polymorphism (0.33) was found in subjects with Type II (non-insulin-dependent) diabetes mellitus (p = 0.02), though adjustment for BMI weakened this significance (p = 0.06). The -3826 G variant was associated with increased fasting glucose (p = 0.01). This was, however, a result of a greater proportion of women with Type II diabetes also having the G variant (p = 0.10, adjusted for Type II diabetes). The -3826 G variant of uncoupling protein-1 did not have an effect on other metabolic variables associated with obesity. CONCLUSION/INTERPRETATION: In overweight Australian women the -3826 G variant of UCP-1 increased the susceptibility to obesity indicating that UCP-1 could be involved in weight regulation.