61 resultados para Obesity - Genetic aspects


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The prevalence of childhood obesity is escalating rapidly and it considered to be a major public health problem. Diet is a recognised precursor of fatness, and current evidence supports the premise that in Westernised countries, the dietary intakes of children are likely to be important in obesity genesis. However, we have a relatively poor understanding of the environments in which a child’s eating is learnt and maintained. Much of the existing work in this area is based on small-scale or experimental studies, or has been derived from homogeneous populations within the USA. Despite these limitations, there is evidence that aspects of the child’s family environment are likely to be important in determining obesity risk in children. This thesis examines the impact of the family food environment on a child’s eating through two related studies. The first study, titled the Children and Family Eating (CAFÉ) study comprised three phases. Phase one involved qualitative interviews with 17 parents of 5-6 year-old children to explore parental perceptions regarding those factors in a child’s environment believed to influence the development of their child’s eating habits. These interviews were used to inform the development of quantitative measures of the family food environment. The second phase involved the development of a Food Frequency Questionnaire (FFQ) to assess dietary intake in 5-6 year-olds. The FFQ was informed by analysis of 1995 Australian National Nutrition Survey data. In the final phase the relationships between dietary intakes of 5-6 year-old children, and potential predictors of dietary intake were examined in a cross-sectional study of 560 families. Predictors included measures of: parental perceptions of the adequacy of their child’s diet; food availability and accessibility; child-feeding; the opportunities for parental modelling of food intake; a child’s television exposure; maternal Body Mass Index; and maternal education. Analysis of the CAFÉ data provides unique information regarding the relationships between a child’s family food environment and their food consumption. Models developed for a range of dietary outcomes considered to be predictive of increased risk for obesity, including total energy and fat intakes, vegetable variety, vegetable consumption, and high-energy (non-dairy) fluid consumption, explained between 11 and 20 percent of the variance in dietary intake. Two aspects of the family food environment, parental perception of a child’s dietary adequacy, and the total minutes of television viewed per day, were frequently found to be predictive of dietary outcomes likely to promote fatness in these children. The second study, titled the Parent Education and Support (PEAS) Feeding Intervention Study, was a prospective pre/post non-randomised intervention trial that assessed the impact of a feeding intervention to 240 first-time mothers of one-year-old children. This intervention focused on one aspect of the family food environment, child-feeding, which has been proposed as influential in the development of obesogenic eating behaviours. In this study, Maternal and Child Health Nurses (MCHNs), using a ‘Division of Responsibility’ model of feeding, taught parents to provide nutritious food at regular intervals and to let children decide if to eat and how much to eat. Thus parents were encourages to food their child without exerting pressure, or employing coercion or rewards (controlling behaviours). The aim was to influence parental attitudes and beliefs regarding child-feeding. Through the use of these feeding techniques, this intervention also aimed to increase the variety of fruits and vegetables a child consumed by teaching parents to persist with offering these foods, over the year of the intervention, in non-emotive environments. Fruits and vegetables were chosen in this intervention because they are likely to be protective in the development of obesity. Analysis of the PEAS data suggests that this low-level feeding intervention, delivered through existing Maternal and Child Health services, was modestly effective in changing parental attitudes and beliefs regarding the feeding of young children. Further, the validity of fruits offered to intervention group children increased. This thesis expands the existing knowledge base by providing a comprehensive analysis of the relative impact of aspects of the family environment on dietary intakes of 5-6 year-olds. Further, the analysis of a feeding intervention in first-time parents provides important insights regarding the potential to influence child-feeding and the impact this may have on the promotion of eating behaviours protective against obesity.

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The technology of modern fermented milk production is not complicated and relies largely on the characteristics of the microorganisms used in its manufacture. Biochemical substances excreted by the starter cultures contribute to the chemical, physical and organoleptic properties of cultured milks. Chemical and organoleptic properties of yoghurt starter cultures have been widely studied over several decades. Conversely the biosynthetic processes and genetic control of the production of viscous extracellular material (slime) by selected thermophillic streptococci is still insufficiently understood. This study attempted to elucidate physiological aspects and the genetic control of slime production. An attempt to chemically induce ropiness was also preformed. Twenty strains of Gram positive, thermo-tolerant, milk dotting, catalase negative cocci were collected from a variety of sources. All strains were identified as Streptococcus thermophilus. Four of the isolates were identified as capable of producing an extracellular, ‘ropy’ capsular material. A negative staining method for highlighting capsular material under light microscopy was described. Ropy isolates displayed thick capsular zones of between 6-8 μm. The isolates graded as non-ropy produced only small capsular zones (less than 2 μm); two variants displayed no capsular material. Instability of the ropy phenotype during subculture and prolonged storage was described for all four ropy isolates at varied temperatures. Instability during transfer was reported as moderate with a loss of no more than 45% of ropy colonies after 15 subcultures at 48°C A significant increase in instability, during transfer, associated with an increase in incubation temperature (37-48°C) was also reported. Prolonged storage of ropy variants over ten days resulted in a drop in the number of ropy colonies. The loss was minimal when cultures were stored at 8°C, but excessive (approaching 100%) at 37°C This suggested the presence of capsular degradative substances. Analysis of the plasmid profiles of 20 strains identified only two strains harboured plasmid DNA. All plasmids were small, less than 23kilobases, and each strain possessed a single plasmid species. Only one ropy strain contained plasmid DNA that was shown, with the aid of curing experiments, not to be linked to production of the ropy phenotype. The amino acid analogue p-fluoro-DL-phenylalanine was unsuccessful in generating ropy colonies from non-ropy variants of Streptococcus thermophilus at low concentrations. Some technological considerations for the use of ropy variants of Streptococcus thermophilus in yoghurt starter cultures were made.

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The focus of this thesis was leptin and its role in the development of obesity and non-insulin-dependent diabetes mellitus (NIDDM). Studies in Psammomys obesus, a polygenic animal model of obesity and NIDDM, showed that ob gene expression and plasma leptin concentration correlated significantly with body weight, percentage body fat and plasma insulin concentration. In addition, plasma leptin concentrations were significantly elevated in insulin resistant Psammomys obesus independent of body weight. Dietary energy restriction from weaning in Psammomys obesus prevented excessive body weight gain, hyperleptinemia and hyperglycemia compared with ad libitum fed animals. Interestingly, 19% of the energy-restricted animals still developed hyperinsulinemia and tended to have increased plasma leplin compared with normoinsulinemic energy-restricted Psammomys obesus. Fasting for 24 hours significantly reduced plasma leptin concentration in lean, insulin-sensitive but not obese, insulin-resistant P. obesus, suggesting a dysregulation in the response of leptin to acute caloric deprivation in these animals. The effects of leptin administration to P. obesus were also investigated. Single daily intraperitoneal injection of 5 mg leptin/kg body weight for 14 days had no significant effect in lean or obese P. obesus. This dose had previously been shown to rapidly and significantly reduce food intake and body weight in ob/ob and wild-type mice, suggesting relative leptin resistance in P. obesus. Acute (8 hour) effects of administration of 5 mg leptin/kg body weight were also investigated. No significant effects on food intake or plasma insulin were detected, however blood glucose concentrations were significantly elevated in obese, glucose intolerant P. obexus, suggesting an exacerbation of insulin resistance in susceptible animals. Treatment of lean, healthy P. obesus with 45 mg leptin/kg body weight/day for 7 days resulted in significant decreases in food intake and percentage body fat, showing that the leptin resistance observed in this species could be overcome by the administration of very large doses of leptin. In another study, leplin was shown to significantly inhibit maximal insulin binding to isolated adipocytes, suggesting that leptin may respresent an important link between obesity and NIDDM. Links between aspects of obesity and NIDDM and polymorphisms in the ob and p3-adrencrgic receptor genes were also investigated in two human populations.

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Diseases in natural ecosystems are often assumed to be less severe than those observed in domestic cropping systems due to the extensive biodiversity exhibited in wild vegetation communities. In Australia, it is this natural biodiversity that is now under threat from Phytophthora cinnamomi. The soilborne Oomycete causes severe decline of native vegetation communities in south-western Victoria, Australia, disrupting the ecological balance of native forest and heathland communities. While the effect of disease caused by P. cinnamomi on native vegetation communities in Victoria has been extensively investigated, little work has focused on the Anglesea healthlands in south-western Victoria. Nothing is known about the population structure of P. cinnamomi at Anglesea. This project was divided into two main components to investigate fundamental issues affecting the management of P. cinnamomi in the Anglesea heathlands. The first component examined the phenotypic characteristics of P. cinnamomi isolates sampled from the population at Anglesea, and compared these with isolates from other regions in Victoria, and also from Western Australia. The second component of the project investigated the effect of the fungicide phosphonate on the host response following infection by P. cinnamomi. Following soil sampling in the Anglesea heathlands, a collection of P, cinnamomi isolates was established. Morphological and physiological traits of each isolate were examined. All isolates were found to be of the A2 mating type. Variation was demonstrated among isolates in the following characteristics: radial growth rate on various nutrient media, sporangial production, and sporangial dimensions. Oogonial dimensions did not differ significantly between isolates. Morphological and physiological variation was rarely dependant on isolate origin. To examine the genetic diversity among isolates and to determine whether phenotypic variation observed was genetically based, Random Amplified Polymorphic DNA (RAPD) analyses were conducted. No significant variation was observed among isolates based on an analysis of molecular variance (AMQVA). The results are discussed in relation to population biology, and the effect of genetic variation on population structure and population dynamics. X australis, an arborescent monocotyledon indigenous to Australia, is highly susceptible to infection by P. cinnamomi. It forms an important component of the heathland vegetation community, providing habitat for native flora and fauna, A cell suspension culture system was developed to investigate the effect of the fungicide phosphonate on the host-pathogen interaction between X. australis and P. cinnamomi. This allowed the interaction between the host and the pathogen to be examined at a cellular level. Subsequently, histological studies using X. australis seedlings were undertaken to support the cellular study. Observations in the cell culture system correlated well with those in the plant. The anatomical structure of X australis roots was examined to assist in the interpretation of results of histopathological studies. The infection of single cells and roots of X. australis, and the effect of phosphonate on the interaction are described. Phosphonate application prior to inoculation with P. cinnamomi reduced the infection of cells in culture and of cells in planta. In particular, phosphonate was found to stimulate the production of phenolic material in roots of X australis seedlings and in cells in suspension cultures. In phosphonate-treated roots of X australis seedlings, the deposition of electron dense material, possibly lignin or cellulose, was observed following infection with P. cinnamomi. It is proposed that this is a significant consequence of the stimulation of plant defence pathways by the fungicide. Results of the study are discussed in terms of the implications of the findings on management of the Anglesea heathlands in Victoria, taking into account variation in pathogen morphology, pathogenicity and genotype. The mode of action of phosphonate in the plant is discussed in relation to plant physiology and biochemistry.

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Current physical activity guidelines need to be modified to incorporate specific recommendations for obese people and consideration needs to be given to greater collaboration among health care providers to provide a multi disciplinary team approach that may be a more effective method of managing obesity and promoting physical activity.

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Background The Romp & Chomp intervention reduced the prevalence of overweight/obesity in pre-school children in Geelong, Victoria, Australia through an intervention promoting healthy eating and active play in early childhood settings. This study aims to determine if the intervention successfully created more health promoting family day care (FDC) environments.
Methods The evaluation had a cross-sectional, quasi-experimental design with the intervention FDC service in Geelong and a comparison sample from 17 FDC services across Victoria. A 45-item questionnaire capturing nutrition- and physical activity-related aspects of the policy, socio-cultural and physical environments of the FDC service was completed by FDC care providers (in 2008) in the intervention (n = 28) and comparison (n = 223) samples.
Results Select results showed intervention children spent less time in screen-based activities (P = 0.03), organized active play (P < 0.001) and free inside play (P = 0.03) than comparison children. There were more rules related to healthy eating (P < 0.001), more care provider practices that supported children’s positive meal experiences (P < 0.001), fewer unhealthy food items allowed (P = 0.05), higher odds of staff being trained in nutrition (P = 0.04) and physical activity (P < 0.001), lower odds of having set minimum times for outside (P < 0.001) and organized (P = 0.01) active play, and of rewarding children with food (P < 0.001).
Conclusions Romp & Chomp improved the FDC service to one that discourages sedentary behaviours and promotes opportunities for children to eat nutritious foods. Ongoing investment to increase children’s physical activity within the setting and improving the capacity and health literacy of care providers is required to extend and sustain the improvements.

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The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.

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Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.

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Features of the built environment are increasingly being recognised as potentially important determinants of obesity. This has come about, in part, because of advances in methodological tools such as Geographic Information Systems (GIS). GIS has made the procurement of data related to the built environment easier and given researchers the flexibility to create a new generation of environmental exposure measures such as the travel time to the nearest supermarket or calculations of the amount of neighbourhood greenspace. Given the rapid advances in the availability of GIS data and the relative ease of use of GIS software, a glossary on the use of GIS to assess the built environment is timely. As a case study, we draw on aspects the food and physical activity environments as they might apply to obesity, to define key GIS terms related to data collection, concepts, and the measurement of environmental features.

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OBJECTIVE--To examine the role of area-level socioeconomic status (SES) on the development of abnormal glucose metabolism (AGM) using national, population-based data.

RESEARCH DESIGN AND METHODS--The Australian Diabetes, Obesity and Lifestyle (AusDiab) study is a national, population-based, longitudinal study of adults aged [greater than or equal to] 25 years. A sample of 4,572 people provided complete baseline (1999 to 2000) and 5-year follow-up (2004 to 2005) data relevant for these analyses. Incident AGM was assessed using fasting plasma glucose and 2-h plasma glucose from oral glucose tolerance tests, and demographic, socioeconomic, and behavioral data were collected by interview and questionnaire. Area SES was defined using the Index of Relative Socioeconomic Disadvantage. Generalized linear mixed models were used to examine the relationship between area SES and incident AGM, with adjustment for covariates and correction for cluster design effects.

RESULTS--Area SES predicted the development of AGM, after adjustment for age, sex, and individual SES. People living in areas with the most disadvantage were significantly more likely to develop AGM, compared with those living in the least deprived areas (odds ratio 1.53; 95% CI 1.07-2.18). Health behaviors (in particular, physical activity) and central adiposity appeared to partially mediate this relationship.

CONCLUSIONS--Our findings suggest that characteristics of the physical, social, and economic aspects of local areas influence diabetes risk. Future research should focus on identifying the aspects of local environment that are associated with diabetes risk and how they might be modified.

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Objective:

The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease.
Subjects:

We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass.
Results:

Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P=4.7 × 10−5). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele.
Conclusions:

Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans.

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A growing goal in the field of metabolism is to determine the impact of genetics on different aspects of mitochondrial function. Understanding these relationships will help to understand the underlying etiology for a range of diseases linked with mitochondrial dysfunction, such as diabetes and obesity. Recent advances in instrumentation, has enabled the monitoring of distinct parameters of mitochondrial function in cell lines or tissue explants. Here we present a method for a rapid and sensitive analysis of mitochondrial function parameters in vivo during zebrafish embryonic development using the Seahorse bioscience XF 24 extracellular flux analyser. This protocol utilizes the Islet Capture microplates where a single embryo is placed in each well, allowing measurement of bioenergetics, including: (i) basal respiration; (ii) basal mitochondrial respiration (iii) mitochondrial respiration due to ATP turnover; (iv) mitochondrial uncoupled respiration or proton leak and (iv) maximum respiration. Using this approach embryonic zebrafish respiration parameters can be compared between wild type and genetically altered embryos (mutant, gene over-expression or gene knockdown) or those manipulated pharmacologically. It is anticipated that dissemination of this protocol will provide researchers with new tools to analyse the genetic basis of metabolic disorders in vivo in this relevant vertebrate animal model.

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Aims
To investigate whether diabetes self-care attitudes, behaviours and perceived burden, particularly related to weight management, diet and physical activity, differ between adults with Type 2 diabetes who are severely obese and matched non-severely obese control subjects.

Methods
The 1795 respondents to the Diabetes MILES—Australia national survey had Type 2 diabetes and reported height and weight data, enabling BMI calculation: 530 (30%) were severely obese (BMI ≥ 35 kg/m2; median BMI = 41.6 kg/m2) and these were matched with 530 control subjects (BMI < 35 kg/m2; median BMI = 28.2 kg/m2). Diabetes self-care behaviours, attitudes and burden were measured with the Diabetes Self-Care Inventory—Revised. Within-group and between-group trends were examined.

Results
The group with BMI ≥ 35 kg/m2 was less likely to achieve healthy diet and exercise targets, placed less importance on diet and exercise recommendations, and found the burden of diet and exercise recommendations to be greater than the group with BMI < 35 kg/m2. The group with BMI ≥ 35 kg/m2 was more likely to be actively trying to lose weight, but found weight control a greater burden. These issues accentuated with increasing obesity and were greatest in those with BMI > 45 kg/m2. There were no between-group differences in other aspects of diabetes self-care: self-monitoring of blood glucose, use of medications and smoking. Moderate-to-severe symptoms of depression were independently associated with reduced likelihood of healthy diet and physical activity, and with greater burden associated with diet, physical activity and weight management.

Conclusions
Severely obese people with diabetes demonstrated self-care attitudes, behaviours and burdens that infer barriers to weight loss. However, other important diabetes self-care behaviours are supported equally by severely obese and non-severely obese individuals.

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Background and objectives: 

The World Health Organization (WHO)’s monitoring of risk factors for non-communicable diseases (NCDs) does not include ’upstream’ monitoring of many aspects of food environments that influence population diets. INFORMAS (International Network for Food and Obesity/NCDs Research, Monitoring and Action Support) is a global network of public-interest organisations and researchers that aims to monitor, benchmark and support public and private sector actions to create healthy food environments and reduce obesity and NCDs. This monitoring of public and private sector policies, and their impacts on the healthiness of food environments, seeks to complement existing WHO monitoring efforts.

Methods:
Monitoring areas are divided into process, impact and outcome modules. The two process modules focus on monitoring and benchmarking the policies and actions of the public and private sector. The seven impact modules focus on monitoring and benchmarking the impact of those policies and actions on key aspects of food environments, such as food composition, labelling, promotion, provision, access, availability, affordability, and trade and investment. The three outcome modules focus on monitoring and evaluating changes in behavioural, dietary, physiological and metabolic risk factors, as well as health outcomes. Some aspects of these outcome components are being developed by WHO as part of their global NCD monitoring framework.

Results:
The development of protocols and pilot testing is planned for 2013-2015. The monitoring framework will be trialled in large and small, and high- and low-income countries globally. Within five years, it is expected that all countries will be invited to collect their own data and contribute those data to a global database for benchmarking food environments. 

Conclusions:
Benchmarking data and good practice exemplars will be communicated to policymakers, civil society and the food industry with the aim of stimulating improvements in the healthiness of food environments.

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Background The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence. Aims and methods This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale. Results PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder. Discussion PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.