Paul Lewandowski

Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet

The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-alpha, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-beta, and PPAR-gamma) and BT (C/EBP-beta), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-gamma genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention.

Cancer cachexia: impact, mechanisms and emerging treatments

Many forms of cancer present with a complex metabolic profile characterised by loss of lean body mass known as cancer cachexia. The physical impact of cachexia contributes to decreased patient quality of life, treatment success and survival due to gross alterations in protein metabolism, increased oxidative stress and systemic inflammation. The psychological impact also contributes to decreased quality of life for both patients and their families. Combination therapies that target multiple pathways, such as eicosapentaenoic acid administered in combination with exercise, appetite stimulants, antioxidants or anti-inflammatories, have potential in the treatment of this complex syndrome and require further development.

Red wine consumption increases antioxidant status and decreases oxidative stress in the circulation of both young and old humans

BackgroundRed wine contains a naturally rich source of antioxidants, which may protect the body from oxidative stress, a determinant of age-related disease. The current study set out to determine the in vivo effects of moderate red wine consumption on antioxidant status and oxidative stress in the circulation.Methods20 young (18–30 yrs) and 20 older (≥ 50 yrs) volunteers were recruited. Each age group was randomly divided into treatment subjects who consumed 400 mL/day of red wine for two weeks, or control subjects who abstained from alcohol for two weeks, after which they crossed over into the other group. Blood samples were collected before and after red wine consumption and were used for analysis of whole blood glutathione (GSH), plasma malondialdehyde (MDA) and serum total antioxidant status.ResultsResults from this study show consumption of red wine induced significant increases in plasma total antioxidant status (P < 0.03), and significant decreases in plasma MDA (P < 0.001) and GSH (P < 0.004) in young and old subjects. The results show that the consumption of 400 mL/day of red wine for two weeks, significantly increases antioxidant status and decreases oxidative stress in the circulationConclusionIt may be implied from this data that red wine provides general oxidative protection and to lipid systems in circulation via the increase in antioxidant status.

Marine polyunsaturated fatty acids and cancer therapy

Polyunsaturated fatty acids (PUFAs) derived from marine sources, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are widely consumed as supplements within the community. However, the use of marine PUFAs in a therapeutic context is also increasing in patients receiving treatment for a range of cancer types. On balance, the literature suggests that marine PUFAs have potential as an effective adjuvant to chemotherapy treatment, may have direct anticancer effects, and may help ameliorate some of the secondary complications associated with cancer. Although a range of doses have been trialled, it would appear that supplementation of fish oil (>3 g per day) or EPA/DHA (>1 g EPA and >0.8 g DHA per day) is associated with positive clinical outcomes. However, further research is still required to determine the mechanisms via which marine PUFAs are mediating their effects. This review summarises our current understanding of marine PUFAs and cancer therapy.

Investigation of telomere lengths measurement by quantitative real-time PCR to predict age

Currently DNA profiling methods only compare a suspects DNA with DNA left at the crime scene. When there is no suspect, it would be useful for the police to be able to predict what the person of interest looks like by analysing the DNA left behind in a crime scene. Determination of the age of the suspect is an important factor in creating an identikit. Human somatic cells gradually lose telomeric repeats with age. This study investigated if one could use a correlation between telomere length and age, to predict the age of an individual from their DNA. Telomere length, in buccal cells, of 167 individuals aged between 1 and 96 years old was measured using real-time quantitative PCR. Telomere length decreased with age (r=-0.185, P<0.05) and the age of an individual could be roughly determined by the following formula: (age=relative telomere length -1.5/-0.005). The regression (R(2)) value between telomere length and age was approximately 0.04, which is too low to be use for forensics. The causes for the presence of large variation in telomere lengths in the population were further investigated. The age prediction accuracies were low even after dividing samples into non-related Caucasians, males and females (5%, 9% and 1%, respectively). Mean telomere lengths of eight age groups representing each decade of life showed non-linear decrease in telomere length with age. There were variations in telomere lengths even among similarly aged individuals aged 26 years old (n=10) and age 54 years old (n=9). Therefore, telomere length measurement by real-time quantitative PCR cannot be used to predict age of a person, due to the presence of large inter-individual variations in telomere lengths.

The impact of supplementing lambs with algae on growth, meat traits and oxidative status

The current study examined the effect of supplementing lambs with algae. Forty, three month old lambs were allocated to receive a control ration based on oats and lupins (n=20) or the control ration with DHA-Gold™ algae (~2% of the ration, n=20). These lambs came from dams previously fed a ration based on either silage (high in omega-3) or oats and cottonseed meal (OCSM: high in omega-6) at joining (dam nutrition, DN). Lamb performance, carcase weight and GR fat content were not affected by treatment diet (control vs algae) or DN (silage vs OSCM). Health claimable omega-3 fatty acids (EPA+DHA) were significantly greater in the LL of lambs fed algae (125±6mg/100g meat) compared to those not fed algae (43±6mg/100g meat) and this effect was mediated by DN. Supplementing with algae high in DHA provides a means of improving an aspect of the health status of lamb meat.

A culturally appropriate diet and lifestyle intervention can successfully treat the components of metabolic syndrome in female Pakistani immigrants residing in Melbourne, Australia

This study was designed to test the effectiveness of a culturally appropriate diet and lifestyle intervention to treat metabolic syndrome in female Pakistani immigrants residing in Melbourne, Australia. Forty Pakistani women with metabolic syndrome (aged 20-50 years) completed a 12-week culturally appropriate diet and exercise program. Results indicate that, before intervention, participants were sedentary, taking 4000 +/- 22.6 steps per day, and had an obese-classified body mass index (BMI) of 29.2 +/- 0.46 kg/m(2) (BMI was categorized in accordance with guidelines specifically designed for Asians) and high waist circumference of 132 +/- 25.95 cm. Participants were hypertensive (systolic, 135 +/- 1.3 mm Hg; diastolic, 86 +/- 0.68 mm Hg), were dyslipidemic (total cholesterol, 6.8 +/- 0.15 mmol/L; triglycerides, 2.9 +/- 0.09 mmol/L), and had elevated blood glucose (6.4 +/- 0.33 mmol/L) and fasting blood insulin (45 +/- 6.3 microU/mL) levels. After the 12-week culturally appropriate intervention, activity increased (8600 +/- 596.7 steps per day, P < .05); and BMI (27.8 +/- 0.45 kg/m(2)), blood pressure (systolic, 125 +/- 1.4 mm Hg; diastolic, 80 +/- 0.6 mm Hg), cholesterol (5.5 +/- 0.1 mmol/L), blood glucose (5.9 +/- 0.33 mmol/L), and blood insulin (24.14 +/- 1.8 microU/mL) levels were all significantly reduced (P < .05). This study revealed that the Pakistani female migrants who had metabolic syndrome and its components can successfully be treated via a culturally appropriate diet and lifestyle intervention. The success of the current program raises the possibility that other high-risk ethnic groups can also be treated with a culturally appropriate program.

Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle

BackgroundCancer cachexia is the progressive loss of skeletal muscle protein that contributes significantly to cancer morbidity and mortality. Evidence of antioxidant attenuation and the presence of oxidised proteins in patients with cancer cachexia indicate a role for oxidative stress. The level of oxidative stress in tissues is determined by an imbalance between reactive oxygen species production and antioxidant activity. This study aimed to investigate the superoxide generating NADPH oxidase (NOX) enzyme and antioxidant enzyme systems in murine adenocarcinoma tumour-bearing cachectic mice.MethodsSuperoxide levels, mRNA levels of NOX enzyme subunits and the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidise (GPx) and catalase was measured in the skeletal muscle of mice with cancer and cancer cachexia. Protein expression levels of NOX enzyme subunits and antioxidant enzyme activity was also measured in the same muscle samples.ResultsSuperoxide levels increased 1.4-fold in the muscle of mice with cancer cachexia, and this was associated with a decrease in mRNA of NOX enzyme subunits, NOX2, p40phox and p67phox along with the antioxidant enzymes SOD1, SOD2 and GPx. Cancer cachexia was also associated with a 1.3-fold decrease in SOD1 and 2.0-fold decrease in GPx enzyme activity.ConclusionDespite increased superoxide levels in cachectic skeletal muscle, NOX enzyme subunits, NOX2, p40phox and p67phox, were downregulated along with the expression and activity of the antioxidant enzymes. Therefore, the increased superoxide levels in cachectic skeletal muscle may be attributed to the reduction in the activity of endogenous antioxidant enzymes.

Postexercise muscle cooling enhances gene expression of PGC-1α

PURPOSE This study aimed to investigate the influence of localized muscle cooling on postexercise vascular, metabolic, and mitochondrial-related gene expression. METHODS Nine physically active males performed 30 min of continuous running at 70% of their maximal aerobic velocity, followed by intermittent running to exhaustion at 100% maximal aerobic velocity. After exercise, subjects immersed one leg in a cold water bath (10°C, COLD) to the level of their gluteal fold for 15 min. The contralateral leg remained outside the water bath and served as control (CON). Core body temperature was monitored throughout the experiment, whereas muscle biopsies and muscle temperature (Tm) measurements were obtained from the vastus lateralis before exercise (PRE), immediately postexercise (POST-EX, Tm only), immediately after cooling, and 3 h postexercise (POST-3H). RESULTS Exercise significantly increased core body temperature (PRE, 37.1°C ± 0.4°C vs POST-EX, 39.3°C ± 0.5°C, P < 0.001) and Tm in both CON (PRE, 33.9°C ± 0.7°C vs POST-EX, 39.1°C ± 0.5°C) and COLD legs (PRE, 34.2°C ± 0.9°C vs POST-EX, 39.4°C ± 0.3°C), respectively (P < 0.001). After cooling, Tm was significantly lower in COLD (28.9°C ± 2.3°C vs 37.0°C ± 0.8°C, P < 0.001) whereas PGC-1α messenger RNA expression was significantly higher in COLD at POST-3H (P = 0.014). Significant time effects were evident for changes in vascular endothelial growth factor (P = 0.038) and neuronal nitric oxide synthase (P = 0.019) expression. However, no significant condition effects between COLD and CON were evident for changes in both vascular endothelial growth factor and neuronal nitric oxide synthase expressions. CONCLUSIONS These data indicate that an acute postexercise cooling intervention enhances the gene expression of PGC-1α and may therefore provide a valuable strategy to enhance exercise-induced mitochondrial biogenesis.

Disruption of pro-oxidant and antioxidant systems with elevated expression of the ubiquitin proteosome system in the cachectic heart muscle of nude mice

BackgroundCurrent research into the mechanisms of organ atrophy associated with cancer cachexia have centred on the loss of skeletal muscle, as it is one of the most profound physical changes of the disease. However, many patients with cancer cachexia also experience significant atrophy of the heart. The mechanisms causing cardiac tissue wastage in cancer cachexia are largely unknown. However, it is believed to involve a number of molecular interactions between the tumour and host. Increased levels of oxidative stress have been found in cancer cachectic skeletal muscle and has been linked to the activation of the ubiquitin proteosome system (UPS). The aim of the current study was to examine the role of oxidative stress and the UPS in the hearts of mice with cancer cachexia.MethodsOxidative damage to DNA (8-OH-2dG), mRNA levels of the ROS-producing enzymes NADPH oxidase (NOX), and xanthine oxidase (XDH), the antioxidant enzyme superoxide dismutase (SOD) and key components of the UPS was measured in the heart of mice with cancer cachexia. Protein expression levels of NOX enzyme subunits and SOD enzyme activity was also measured in the same heart samples.Results8-OH-2dG levels were 1.5-fold higher in the heart of mice with cancer cachexia, and this was associated with a 1.7-fold lower level of NOX2 mRNA and twofold higher XDH mRNA in the same hearts. Cancer cachexia was also associated with a 1.5-fold lower level of SOD activity in the heart. Accompanying these pro- and antioxidant differences was a significantly higher level of mRNA for the key UPS elements MURF-1 (4.3=fold) and MAFbx (3.8-fold) in the hearts of mice with cancer cachexia.ConclusionsThe current study demonstrated that cardiac atrophy of cachectic mice is associated with oxidative damage to DNA in the myocardium. The higher levels of XDH mRNA in cachectic hearts suggest that xanthine oxidase may have an important role to play in producing oxidative stress. It appears that the combination of higher XDH expression and lower SOD enzyme activity are key contributors to oxidative stress and cardiac tissue damage in cancer-induced cardiac atrophy. Oxidative stress in the myocardium as with skeletal muscle may also induce increased expression of the E3 ligases MURF-1 and MAFbx as seen in this study.