Andrew Fenning

High-carbohydrate high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats.

The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

Diabetes Self-Management Smartphone Application for Adults With Type 1 Diabetes: Randomized Controlled Trial

Background Persistently poor glycemic control in adult type 1 diabetes patients is a common, complex, and serious problem initiating significant damage to the cardiovascular, renal, neural, and visual systems. Currently, there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores. Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group randomized controlled trial. Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia. In a 6-month intervention, followed by a three-month follow-up, patients (n=72) were randomized to usual care (control group) or usual care and the use of a smartphone application (Glucose Buddy) with weekly text-message feedback from a Certified Diabetes Educator (intervention group). All outcome measures were collected at baseline and every three months over the study period. Patients’ glycosylated hemoglobin levels (HbA1c) were measured with a blood test and diabetes-related self-efficacy, self-care activities, and quality of life were measured with online questionnaires. Results The mean age of patients was 35.20 years (SD 10.43) (28 male, 44 female), 39% (28/72) were male, and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years (SD 9.66). Of the initial 72 patients, 53 completed the study (25 intervention, 28 control group). The intervention group significantly improved glycemic control (HbA1c) from baseline (mean 9.08%, SD 1.18) to 9-month follow-up (mean 7.80%, SD 0.75), compared to the control group (baseline: mean 8.47%, SD 0.86, follow-up: mean 8.58%, SD 1.16). No significant change over time was found in either group in relation to self-efficacy, self-care activities, and quality of life. Conclusions In adjunct to usual care, the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12612000132842; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000132842 (Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u).

Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats

Background and purpose:  Histone deacetylases (HDACs) silence genes by deacetylating lysine residues in histones and other proteins. HDAC inhibitors represent a new class of compounds with anti‐inflammatory activity. This study investigated whether treatment with a broad spectrum HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), would prevent cardiac fibrosis, part of the cardiovascular remodelling in deoxycorticosterone acetate (DOCA)‐salt rats.

Cardiac adaptation to endurance exercise in rats

AbstractEndurance exercise is widely assumed to improve cardiac function in humans. This project has determined cardiac function following endurance exercise for 6 (n = 30) or 12 (n = 25) weeks in male Wistar rats (8 weeks old). The exercise protocol was 30 min/day at 0.8 km/h for 5 days/week with an endurance test on the 6th day by running at 1.2 km/h until exhaustion. Exercise endurance increased by 318% after 6 weeks and 609% after 12 weeks. Heart weight/kg body weight increased by 10.2% after 6 weeks and 24.1% after 12 weeks. Echocardiography after 12 weeks showed increases in left ventricular internal diameter in diastole (6.39 ± 0.32 to 7.90 ± 0.17 mm), systolic volume (49 ± 7 to 83 ± 11 μl) and cardiac output (75 ± 3 to 107 ± 8 ml/min) but not left wall thickness in diastole (1.74 ± 0.07 to 1.80 ± 0.06 mm). Isolated Langendorff hearts from trained rats displayed decreased left ventricular myocardial stiffness (22 ± 1.1 to 19.1 ± 0.3) and reduced purine efflux during pacing-induced workload increases. 31P-NMR spectroscopy in isolated hearts from trained rats showed decreased PCr and PCr/ATP ratios with increased creatine, AMP and ADP concentrations. Thus, this endurance exercise protocol resulted in physiological hypertrophy while maintaining or improving cardiac function. (Mol Cell Biochem 251: 51–59, 2003)

Effects of high-intensity interval training on cardiometabolic health: a systematic review and meta-analysis of intervention studies

The current review clarifies the cardiometabolic health effects of high-intensity interval training (HIIT) in adults. A systematic search (PubMed) examining HIIT and cardiometabolic health markers was completed on 15 October 2015. Sixty-five intervention studies were included for review and the methodological quality of included studies was assessed using the Downs and Black score. Studies were classified by intervention duration and body mass index classification. Outcomes with at least 5 effect sizes were synthesised using a random-effects meta-analysis of the standardised mean difference (SMD) in cardiometabolic health markers (baseline to postintervention) using Review Manager 5.3. Short-term (ST) HIIT (<12 weeks) significantly improved maximal oxygen uptake (VO2 max; SMD 0.74, 95% CI 0.36 to 1.12; p<0.001), diastolic blood pressure (DBP; SMD −0.52, 95% CI −0.89 to −0.16; p<0.01) and fasting glucose (SMD −0.35, 95% CI −0.62 to −0.09; p<0.01) in overweight/obese populations. Long-term (LT) HIIT (≥12 weeks) significantly improved waist circumference (SMD −0.20, 95% CI −0.38 to −0.01; p<0.05), % body fat (SMD −0.40, 95% CI −0.74 to −0.06; p<0.05), VO2 max (SMD 1.20, 95% CI 0.57 to 1.83; p<0.001), resting heart rate (SMD −0.33, 95% CI −0.56 to −0.09; p<0.01), systolic blood pressure (SMD −0.35, 95% CI −0.60 to −0.09; p<0.01) and DBP (SMD −0.38, 95% CI −0.65 to −0.10; p<0.01) in overweight/obese populations. HIIT demonstrated no effect on insulin, lipid profile, C reactive protein or interleukin 6 in overweight/obese populations. In normal weight populations, ST-HIIT and LT-HIIT significantly improved VO2 max, but no other significant effects were observed. Current evidence suggests that ST-HIIT and LT-HIIT can increase VO2 max and improve some cardiometabolic risk factors in overweight/obese populations.

Cardiovascular changes during maturation and ageing in male and female spontaneously hypertensive rats

Background: Cardiovascular remodeling leading to heart failure is common in the elderly. Testing effective pharmacological treatment of human heart failure requires a suitable animal model that adequately mimics the human disease state. Methods: This study has characterized the structural, functional, and electrical characteristics of the cardiovascular system throughout the lifespan in male and female spontaneously hypertensive rats (SHRs), a genetic model of chronic hypertension-induced cardiovascular remodeling, and age- and gender-matched normotensive controls, to determine whether ageing SHRs mimic the changes seen in ageing humans. Results: Both the ageing male and female SHRs developed progressive hypertension, ventricular hypertrophy, left ventricular fibrosis, action potential prolongation without impaired glucose tolerance. Male SHRs from 15 months of age exhibited left ventricular wall thinning and chamber dilation, together with systolic and diastolic dysfunction and increased cardiac stiffness and increased erythrocyte superoxide production, which were not present in the female SHRs. Conclusion: Ageing male SHRs in contrast to the female SHRs, better mimic the chronic heart failure in humans produced by chronic hypertension. Ageing male SHRs could then be used to investigate proposed therapeutic interventions for chronic congestive heart failure in humans.

Whole-Body Vibration Effects on Bone Mineral Density in Women with or Without Resistance Training

INTRODUCTION Whole-body vibration exposure may translate into improved bone mass in young adult women. The primary focus of this study was to examine the effects of graded whole-body vibration or vibration exposure plus resistance training on bone mineral density (BMD), hematological measures for bone remodeling, and exercise metabolism in young women. METHODS There were 51 healthy active women [mean (SD) age, 21.02 (3.39) yr; height, 165.66 (6.73) cm; body mass 66.54 (13.39) kg] who participated in the intervention. Subjects were randomly assigned to whole-body vibration (WBV), whole-body vibration plus resistance training (WBV+RT), or control (CONT) groups for 16 wk. RESULTS A repeated-measure ANOVA found no significant (P < 0.05) group differences in BMD at the completion of 16 wk. A significant within group change was apparent for the WBV (2.7% femoral neck) and WBV+RT (femoral neck 1.9%; vertebra 0.98%). WBV and WBV+RT experienced a significant (P < 0.05) 60% and 58% increase in adiponectin, 48% and 30% in transforming growth factor-beta1, and 17% and 34% in nitric oxide with an accompanying 50% and 36% decrease in osteopontin, 19% and 34% in interleukin-1beta, and 38% and 39% in tumor necrosis factor-alpha. CONCLUSIONS The results indicate graded whole-body vibration exposure may be effective in improving BMD by increasing bone deposition while also decreasing bone resorption. Whole-body vibration may also provide an efficient stratagem for young women to achieve peak bone mass and help stave off osteoporosis later in life and provide a novel form of physical training.

Reversal of cardiac dysfunction by selective ET-A receptor antagonism

The effectiveness of a selective endothelin receptor‐A (ET‐A) antagonist, A‐127722 (approximately 10 mg kg−1 day−1 as 200 mg kg−1 powdered food), to reverse existing cardiac remodelling and prevent further remodelling was tested in deoxycorticosterone acetate (DOCA)‐salt hypertensive rats. Uninephrectomised rats (UNX) administered DOCA (25 mg every fourth day s.c.) and 1% NaCl in drinking water for 28 days developed hypertension (systolic blood pressure (BP): UNX 128±6 mmHg, DOCA‐salt 182±5* mmHg; *P<0.05 vs UNX), left ventricular hypertrophy (UNX 1.99±0.06 mg kg−1 body wt, DOCA‐salt 3.30±0.08* mg kg−1 body wt), decreased left ventricular internal diameter (UNX 6.69±0.18 mm, DOCA‐salt 5.51±0.37* mm), an increased left ventricular monocyte/macrophage infiltration together with an increased interstitial collagen from 2.7±0.3 to 11.7±1.3%, increased passive diastolic stiffness (UNX 21.1±0.5, DOCA‐salt 30.1±1.3*), prolongation of the action potential duration at 20 and 90% of repolarisation (APD20–UNX 6.8±1.1, DOCA‐salt 10.1±1.5* ms; APD90–UNX 34.4±3.5 ms, DOCA‐salt 64.3±10.4* ms) and vascular dysfunctions (2.6‐fold decrease in maximal contractile response to noradrenaline, 3.5‐fold decrease in maximal relaxation response to acetylcholine). Administration of A‐127722 for 14 days starting 14 days after surgery attenuated the increases in systolic BP (150±6** mmHg, **P<0.05 vs DOCA‐salt), left ventricular wet weight (2.65±0.06** mg kg−1 body wt) and internal diameter (6.39±0.31** mm), prevented left ventricular monocyte/macrophage accumulation, attenuated the increased left ventricular interstitial collagen (7.6±1.3%**), reversed the increased passive diastolic stiffness (22.1±1.2**), attenuated the action potential duration prolongation (APD20 – 7.6±1.4**, APD90 – 41.5±6.9** ms) and normalised changes in vascular function. ET‐A receptor antagonism both reverses and prevents the cardiac and vascular remodelling in DOCA‐salt hypertension and improves cardiovascular function.

Antioxidant supplementation enhances erythrocyte antioxidant status and attenuates cyclosporine-induced vascular dysfunction.

The aim of this study was to determine the effects of dietary antioxidant supplementation with α‐tocopherol and α‐lipoic acid on cyclosporine‐induced alterations to erythrocyte and plasma redox balance, and cyclosporine‐induced endothelial and smooth muscle dysfunction. Rats were randomly assigned to either control, antioxidant, cyclosporine or cyclosporine + antioxidant treatments. Cyclosporine A was administered for 10 days after an 8‐week feeding period. Plasma was analyzed for α‐tocopherol, total antioxidant capacity, malondialdehyde and creatinine. Erythrocytes were analyzed for glutathione, methemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose‐6‐phosphate dehydrogenase, α‐tocopherol and malondialdehye. Vascular endothelial and smooth muscle function was determined in vitro. Antioxidant supplementation resulted in significant increases in erythrocyte α‐tocopherol concentration and glutathione peroxidase activity in both of the antioxidant‐supplemented groups. Cyclosporine administration caused significant decreases in glutathione concentration, methemoglobin concentration and superoxide dismutase activity. Antioxidant supplementation attenuated the cyclosporine‐induced decrease in superoxide dismutase activity. Cyclosporine therapy impaired both endothelium‐independent and ‐dependent relaxation of the thoracic aorta, and this was attenuated by antioxidant supplementation. In summary, dietary supplementation with α‐tocopherol and α‐lipoic acid attenuated the cyclosporine‐induced decrease in erythrocyte superoxide dismutase activity and attenuated cyclosporine‐induced vascular dysfunction.

Effects of Light Intensity Activity on CVD Risk Factors: A Systematic Review of Intervention Studies.

The effects of light intensity physical activity (LIPA) on cardiovascular disease (CVD) risk factors remain to be established. This review summarizes the effects of LIPA on CVD risk factors and CVD-related markers in adults. A systematic search of four electronic databases (PubMed, Academic Search Complete, SPORTDiscus, and CINAHL) examining LIPA and CVD risk factors (body composition, blood pressure, glucose, insulin, glycosylated hemoglobin, and lipid profile) and CVD-related markers (maximal oxygen uptake, heart rate, C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and tumor necrosis factor receptors 1 and 2) published between 1970 and 2015 was performed on 15 March 2015. A total of 33 intervention studies examining the effect of LIPA on CVD risk factors and markers were included in this review. Results indicated that LIPA did not improve CVD risk factors and CVD-related markers in healthy individuals. LIPA was found to improve systolic and diastolic blood pressure in physically inactive populations with a medical condition. Reviewed studies show little support for the role of LIPA to reduce CVD risk factors. Many of the included studies were of low to fair study quality and used low doses of LIPA. Further studies are needed to establish the value of LIPA in reducing CVD risk.