Adipose tissue and cardiovascular and metabolic diseases

Obesity is a major contributor to the rising prevalence of cardiovascular and metabolic diseases in both the developed and developing world. Increased adipose tissue mass is associated with changes to the structure and function of the cardiovascular system to ensure circulatory requirements are met. Adipose tissue is a metabolically active endocrine organ that is capable of synthesizing and releasing a variety of signal proteins (adipokines), many of which impact unfavorably on both the cardiovascular system and metabolism. The extent of adiposity, location of fat deposits and variations in the secretion of adipokines, along with other factors, determine whether a particular obese person develops complications, including type 2 diabetes, coronary artery disease, congestive heart failure, hypertension, obstructive sleep apnea syndrome, and non-alcoholic fatty liver disease. This review will discuss the relationship between obesity and cardiovascular and metabolic diseases and will explore how complications of obesity impact on mortality, while healthy lifestyle may prevent them.Biomedical Reviews 2006; 17: 89-104

Optimizing IVF outcomes in the genomics era

In order to optimize pregnancy rates during IVF cycle, we have to grow embryos in such a way to allow them to reach their full potential in-vitro. As IVF has evolved since the first live birth in 1978, culture conditions have improved and we have reached a stage where embryos can thrive to the blastocyst stage in-vitro if programmed to do so. IVF cycles typically produce multiple embryos during one cycle. Establishing which embryo has a higher potential to result in a live birth than its sibling embryos has been attempted over the last 30 years by using non-invasive and invasive techniques. Methods to choose which embryo to transfer range from basic morphology to establishing ploidy status of each embryo by biopsy. Aneuploidy is the most common cause of implantation failure and miscarriage in human reproduction and increases with maternal age, however all maternal ages exhibit varying degrees of embryonic aneuploidy. While some non-invasive techniques have shown promise in predicting which embryos have the highest implantation potential, the only way currently to establish ploidy status of embryos in the embryology lab is to biopsy, then assay embryonic cells before transfer. To improve IVF success, original studies derived from retrospective analysis of clinic data, or prospectively designed studies are essential and a number of fundamental biological questions pertaining to chromosome abnormalities and their relationship to IVF embryo development remain unanswered. The overall aim of this thesis was thus to provide further insight into the cytogenetic basis of early human development by pursuit of the following specific aims: (1) To test the hypothesis that we can predict aneuploidy levels in human IVF embryos without embryo biopsy for PGS by analysis of basic morphokinetic criteria and spent media from cell free embryonic DNA, (2) to test the hypothesis that the ICSI technique may create aneuploidy in embryos, (3) to establish novel patient populations that may benefit from the use of PGS, specifically male factor infertility patients and young oocyte donors, (4) conducting a randomized controlled trial (RCT) to establish the optimal transfer strategy (fresh vs frozen) for euploid embryos in patients using their own oocytes,(5) to test the hypothesis that identifying mosaic embryos among a cohort of embryos could increase live birth rates and reduce miscarriage rates by avoiding these embryos for transfer and (6) to use the data generated from PGS/IVF cycles to provide a framework for creating realistic expectations for patients planning for their fertility future. The conclusions of each aim were as follows: I demonstrated that poorer quality embryos showed an increased rate of aneuploidy but not large enough to predict aneuploidy for each individual embryo. Analysis of cell free DNA in spent culture media is at its early stages of development, but the study presented in this chapter using a novel WGA technique, showed that there is potential for its future use as a non-invasive PGS method. I found that aneuploidy rates were similar in embryos generated from normal sperm whether they were created using ICSI or standard insemination using a donor oocyte model to minimize the maternal age effect (aneuploidy rates of 21% for standard IVF vs 23% for ICSI. P=>0.05 NS) concluding that the ICSI technique does not create embryonic aneuploidy. Donor oocyte recipients (average age of donor 25) benefited from PGS in cryopreserved embryo transfer cycles by significantly increasing live birth rates per embryo from 36% with no PGS to 59% per PGS screened embryo (p=0.0008). Male factor infertility patients presenting with oligozoospermia, were shown to exhibit a significantly higher incidence of sex chromosome abnormalities in pre-implantation embryos compared to patients with normal sperm using ICSI (6.1% for oligozoospermic samples vs 1.6% for normal semen samples. P=0.0007). Both of these patient groups could benefit from offering PGS as part of their IVF cycle. The RCT showed that freeze all cycles had higher live birth rates than fresh cycles (77% of frozen embryo transfers vs 59% of fresh embryo transfers. P=0.04). When comparing transfer of embryos screened by NGS with those screened by aCGH, the conclusion in the relatively small subset of patients was that live birth rates for embryos screened with aCGH and NGS appear to be similar, with a 2% trend in favor of NGS (61% aCGH vs 63% NGS live born offspring per embryo transferred. P=>0.05 NS). Lastly, the retrospective analysis of data using PGS cycles to calculate how many oocytes are required to create one euploid blastocyst depending on maternal age, resulted in a useful tool to advise patients on how many cycles of IVF they may need to complete their family. Taken together therefore, this thesis provides fundamental insight into the chromosomal basis of early human development, introduces new referral categories for PGS and informs the practical use of IVF/PGS in the future

The Impact of Altered Timing of Eating, Sleep and Work Patterns on Human Health

Some 20% of the population is required to work outside the regular 9:00 a.m.–5:00 p.m. working day, and this number is likely to increase as economic demands push work hours into the night for many companies. These irregular schedules mean workers often have to sleep during the day and be awake at night. This causes a misalignment between normal day-light entrained internal physiological processes, such as metabolism and digestion, and the external environment. As a direct consequence, night workers have poorer health than day workers, even after controlling for lifestyle and socioeconomic status. The purpose of this Special Issue is to highlight the interrelationships between timing of food intake and diet quality with sleep and work patterns in humans with an emphasis on randomized controlled trials or meta-analyses of data from published studies

Relationships between Obesity, Cardiorespiratory Fitness, and Cardiovascular Function

Background. Obesity and low cardiorespiratory fitness (CRF) have been shown to independently increase the risk of CVD mortality. The aim of this study was to investigate the relationship between CRF, body fatness and markers of arterial function. Method and Results. Obese (9 male, 18 female; BMI 35.3 ± 0.9 kg·m−2) and lean (8 male, 18 female; BMI 22.5 ± 0.3 kg·m−2) volunteers were assessed for body composition (DXA), cardiorespiratory fitness (predicted V˙O2max), blood pressure (BP), endothelial vasodilatator function (FMD), and arterial compliance (AC) (via radial artery tonometry). The obese group had more whole body fat and abdominal fat (43.5 ± 1.2% versus 27.2 ± 1.6%; P < .001 and 48.6 ± 0.9% versus 28.9 ± 1.8%; P < .001, resp.), and lower FMD (3.2 ± 0.4% versus 5.7 ± 0.7%; P < .01) than the lean subjects, but there was no difference in AC. AC in large arteries was positively associated with CRF (R = 0.5; P < .01) but not with fatness. Conclusion. These results indicate distinct influences of obesity and CRF on blood vessel health. FMD was impaired with obesity, which may contribute to arterial and metabolic dysfunction. Low CRF was associated with reduced elasticity in large arteries, which could result in augmentation of aortic afterload

Protein hydrolysates and recovery of muscle damage following eccentric exercise

Background: A whey protein hydrolysate (NatraBoost XR; WPHNB) has been shown to speed repair muscle damage. We sought to determine whether this benefit is specific to this hydrolysate to evaluate a marker for quality control. Methods: Three hydrolysates of the same whey protein isolate (WPI) were prepared (WPHNB, WPH1 and WPH2). Isometric knee extensor strength was measured in 39 sedentary male participants before and after 100 maximal eccentric contractions of the knee extensors to induce muscle damage. Participants were then randomised to consume 250 ml of flavoured water (FW, n=9), or 250 ml of FW containing 25 g of either NatraBoost XR (n=3), WPH1 (n=9), WPH2 (n=9) or WPI (n=9). Strength was reassessed over the next seven days while the supplements were consumed daily. Fibroblasts were cultured for 48 hr in the presence of the different hydrolysates, WPI, saline or fetal bovine serum to ascertain effects on cell proliferation. Results: Strength was reduced in all treatment groups after eccentric exercise (P<0.001). Strength recovered steadily over 7 days in the FW, WPI, WPH1 and WPH2 treatment groups (P<0.001), with no difference between treatments (P=0.87). WPHNB promoted faster strength recovery compared with the other treatments (P<0.001). Fibroblast proliferation was greater with WPHNB compared with saline, WPI or the other hydrolysates (P<0.001). Conclusions: Promoting recovery from muscle damage seems unique to WPHNB. In vitro fibroblast proliferation may be a useful marker for quality control. It is not clear whether effects on fibroblast proliferation contribute to the in vivo effect of WPHNB on muscle damage

Effects of eating fresh lean pork on cardiometabolic health parameters

High protein meat-based diets are commonly promoted for weight loss, supposedly by increasing satiety and energy expenditure. Pork is a good source of protein however little information on the metabolic effects of pork consumption exists. This pilot study aimed to examine whether regular consumption of fresh lean pork could improve body composition and cardiovascular risk factors in a 6 month parallel intervention trial. 164 overweight adults (mean BMI 32) were randomly assigned to incorporate up to 1 kg pork/week by substituting for other foods or maintain their habitual diet (control). Plasma levels of lipids, glucose and insulin, BMI, waist/hip circumference, blood pressure, heart rate and arterial compliance were measured at baseline and 3 and 6 months. Body composition was determined using dual energy X-ray absorptiometry. A total of 144 volunteers completed and volunteers in the pork group increased their intake 10 fold by substituting pork for mainly beef and chicken. After 3 months, there were significant (p ≤ 0.01) reductions in weight, BMI, waist circumference, % body fat, fat mass and abdominal fat in the pork group relative to controls, which persisted for 6 months. There was no change in lean mass, indicating that the reduction in weight was due to loss of fat mass. There were no significant effects on other metabolic parameters. Regular consumption of lean fresh pork may improve body composition

Feasibility of omega-3 fatty acid supplementation as an adjunct therapy for people with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial

There is evidence to support the use of supplementation with long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) from oily fish or fish oil for the treatment of various inflammatory diseases such as rheumatoid arthritis. Chronic obstructive pulmonary disease (COPD) is a progressive, terminal disease characterized by persistent airflow limitation, lung and systemic inflammation. To date, one randomized controlled trial has been published that assessed the efficacy of LCn-3PUFA in people with this condition. The aim of this article is to discuss the feasibility of conducting a trial to evaluate fish oil supplementation as adjunct therapy in people with COPD.The study is supported by a University of South Australia, Division of Health Sciences grant (DRDG 2011 (round 2))

Dairy foods and dairy protein consumption is inversely related to markers of adiposity in obese men and women

A number of intervention studies have reported that the prevalence of obesity may be in part inversely related to dairy food consumption while others report no association. We sought to examine relationships between energy, protein and calcium consumption from dairy foods (milk, yoghurt, cheese, dairy spreads, ice-cream) and adiposity including body mass index (BMI), waist (WC) and hip circumference (HC), and direct measures of body composition using dual energy X-ray absorptiometry (% body fat and abdominal fat) in an opportunistic sample of 720 overweight/obese Australian men and women. Mean (SD) age, weight and BMI of the population were 51 ± 10 year, 94 ± 18 kg and 32.4 ± 5.7 kg/m2, respectively. Reduced fat milk was the most commonly consumed dairy product (235 ± 200 g/day), followed by whole milk (63 ± 128 g/day) and yoghurt (53 ± 66 g/day). Overall dairy food consumption (g/day) was inversely associated with BMI, % body fat and WC (all p < 0.05). Dairy protein and dairy calcium (g/day) were both inversely associated with all adiposity measures (all p < 0.05). Yoghurt consumption (g/day) was inversely associated with % body fat, abdominal fat, WC and HC (all p < 0.05), while reduced fat milk consumption was inversely associated with BMI, WC, HC and % body fat (all p < 0.05). Within a sample of obese adults, consumption of dairy products, dairy protein, and calcium was associated with more favourable body composition