LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion

Summary Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. © 2015 The Authors.

Fascial planes within subcutaneous fat in humans

We have used B-mode (brightness-mode) ultrasound to investigate the fascial planes within subcutaneous fat at the triceps and abdominal sites in a group of 17 women attending a weight control group over a 12 month period. In most subjects there was a single intralipid fascial plane at each site. As the thickness of adipose tissue increased, most of the change at the abdominal site was in the deep rather than the superficial layer of fat. At the triceps site both deep and superficial layers increased. Our findings confirm the presence of two different layers in human subcutaneous fat at the triceps and abdominal sites. These layers have been shown to be functionally different in animals and our study supports this in humans at the abdominal site.

High body mass index is not a barrier to physical activity: Analysis of international rugby players' anthropometric data

Recent data indicate that levels of overweight and obesity are increasing at an alarming rate throughout the world. At a population level (and commonly to assess individual health risk), the prevalence of overweight and obesity is calculated using cut-offs of the Body Mass Index (BMI) derived from height and weight. Similarly, the BMI is also used to classify individuals and to provide a notional indication of potential health risk. It is likely that epidemiologic surveys that are reliant on BMI as a measure of adiposity will overestimate the number of individuals in the overweight (and slightly obese) categories. This tendency to misclassify individuals may be more pronounced in athletic populations or groups in which the proportion of more active individuals is higher. This differential is most pronounced in sports where it is advantageous to have a high BMI (but not necessarily high fatness). To illustrate this point we calculated the BMIs of international professional rugby players from the four teams involved in the semi-finals of the 2003 Rugby Union World Cup. According to the World Health Organisation (WHO) cut-offs for BMI, approximately 65% of the players were classified as overweight and approximately 25% as obese. These findings demonstrate that a high BMI is commonplace (and a potentially desirable attribute for sport performance) in professional rugby players. An unanswered question is what proportion of the wider population, classified as overweight (or obese) according to the BMI, is misclassified according to both fatness and health risk? It is evident that being overweight should not be an obstacle to a physically active lifestyle. Similarly, a reliance on BMI alone may misclassify a number of individuals who might otherwise have been automatically considered fat and/or unfit.

A systematic review of environmental correlates of obesity-related dietary behaviors in youth

There is increasing interest in the role the environment plays in shaping the dietary behavior of youth, particularly in the context of obesity prevention. An overview of environmental factors associated with obesity-related dietary behaviors among youth is needed to inform the development of interventions. A systematic review of observational studies on environmental correlates of energy, fat, fruit/ vegetable, snack/fast food and soft drink intakes in children (4–12 years) and adolescents (13–18 years) was conducted. The results were summarized using the analysis grid for environments linked to obesity. The 58 papers reviewed mostly focused on sociocultural and economical–environmental factors at the household level. The most consistent associations were found between parental intake and children’s fat, fruit/vegetable intakes, parent and sibling intake with adolescent’s energy and fat intakes and parental education with adolescent’s fruit/ vegetable intake. A less consistent but positive association was found for availability and accessibility on children’s fruit/vegetable intake. Environmental factors are predominantly studied at the household level and focus on sociocultural and economic aspects. Most consistent associations were found for parental influences (parental intake and education).More studies examining environmental factors using longitudinal study designs and validated measures are needed for solid evidence to inform interventions.

Non-alcoholic fatty liver disease : can ultrasound assist in early diagnosis of prediabetes and delay progression to type2 diabetes mellitus

Non Alcoholic Fatty Liver Disease (NAFLD) is a condition that is frequently seen but seldom investigated. Until recently, NAFLD was considered benign, self-limiting and unworthy of further investigation. This opinion is based on retrospective studies with relatively small numbers and scant follow-up of histology data. (1) The prevalence for adults, in the USA is, 30%, and NAFLD is recognized as a common and increasing form of liver disease in the paediatric population (1). Australian data, from New South Wales, suggests the prevalence of NAFLD in “healthy” 15 year olds as being 10%.(2) Non-alcoholic fatty liver disease is a condition where fat progressively invades the liver parenchyma. The degree of infiltration ranges from simple steatosis (fat only) to steatohepatitis (fat and inflammation) steatohepatitis plus fibrosis (fat, inflammation and fibrosis) to cirrhosis (replacement of liver texture by scarred, fibrotic and non functioning tissue).Non-alcoholic fatty liver is diagnosed by exclusion rather than inclusion. None of the currently available diagnostic techniques -liver biopsy, liver function tests (LFT) or Imaging; ultrasound, Computerised tomography (CT) or Magnetic Resonance Imaging (MRI) are specific for non-alcoholic fatty liver. An association exists between NAFLD, Non Alcoholic Steatosis Hepatitis (NASH) and irreversible liver damage, cirrhosis and hepatoma. However, a more pervasive aspect of NAFLD is the association with Metabolic Syndrome. This Syndrome is categorised by increased insulin resistance (IR) and NAFLD is thought to be the hepatic representation. Those with NAFLD have an increased risk of death (3) and it is an independent predictor of atherosclerosis and cardiovascular disease (1). Liver biopsy is considered the gold standard for diagnosis, (4), and grading and staging, of non-alcoholic fatty liver disease. Fatty-liver is diagnosed when there is macrovesicular steatosis with displacement of the nucleus to the edge of the cell and at least 5% of the hepatocytes are seen to contain fat (4).Steatosis represents fat accumulation in liver tissue without inflammation. However, it is only called non-alcoholic fatty liver disease when alcohol - >20gms-30gms per day (5), has been excluded from the diet. Both non-alcoholic and alcoholic fatty liver are identical on histology. (4).LFT’s are indicative, not diagnostic. They indicate that a condition may be present but they are unable to diagnosis what the condition is. When a patient presents with raised fasting blood glucose, low HDL (high density lipoprotein), and elevated fasting triacylglycerols they are likely to have NAFLD. (6) Of the imaging techniques MRI is the least variable and the most reproducible. With CT scanning liver fat content can be semi quantitatively estimated. With increasing hepatic steatosis, liver attenuation values decrease by 1.6 Hounsfield units for every milligram of triglyceride deposited per gram of liver tissue (7). Ultrasound permits early detection of fatty liver, often in the preclinical stages before symptoms are present and serum alterations occur. Earlier, accurate reporting of this condition will allow appropriate intervention resulting in better patient health outcomes. References 1. Chalasami N. Does fat alone cause significant liver disease: It remains unclear whether simple steatosis is truly benign. American Gastroenterological Association Perspectives, February/March 2008 www.gastro.org/wmspage.cfm?parm1=5097 Viewed 20th October, 2008 2. Booth, M. George, J.Denney-Wilson, E: The population prevalence of adverse concentrations with adiposity of liver tests among Australian adolescents. Journal of Paediatrics and Child Health.2008 November 3. Catalano, D, Trovato, GM, Martines, GF, Randazzo, M, Tonzuso, A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study .Liver Int.2008; February 1280-9 4. Choudhury, J, Sanysl, A. Clinical aspects of Fatty Liver Disease. Semin in Liver Dis. 2004:24 (4):349-62 5. Dionysus Study Group. Drinking factors as cofactors of risk for alcohol induced liver change. Gut. 1997; 41 845-50 6. Preiss, D, Sattar, N. Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci.2008; 115 141-50 7. American Gastroenterological Association. Technical review on nonalcoholic fatty liver disease. Gastroenterology.2002; 123: 1705-25

Improvements in sustainable energy and water practice in the food processing industry : an in depth analysis of the manufacture of Ghee at the Butter Producers' Cooperative Federation Limited, Brisbane

This thesis is a documented energy audit and long term study of energy and water reduction in a ghee factory. Global production of ghee exceeds 4 million tonnes annually. The factory in this study refines dairy products by non-traditional centrifugal separation and produces 99.9% pure, canned, crystallised Anhydrous Milk Fat (Ghee). Ghee is traditionally made by batch processing methods. The traditional method is less efficient, than centrifugal separation. An in depth systematic investigation was conducted of each item of major equipment including; ammonia refrigeration, a steam boiler, canning equipment, pumps, heat exchangers and compressed air were all fine-tuned. Continuous monitoring of electrical usage showed that not every initiative worked, others had pay back periods of less than a year. In 1994-95 energy consumption was 6,582GJ and in 2003-04 it was 5,552GJ down 16% for a similar output. A significant reduction in water usage was achieved by reducing the airflow in the refrigeration evaporative condensers to match the refrigeration load. Water usage has fallen 68% from18ML in 1994-95 to 5.78ML in 2003-04. The methods reported in this thesis could be applied to other industries, which have similar equipment, and other ghee manufacturers.

The NOURISH randomised control trial : positive feeding practices and food preferences in early childhood - a primary prevention program for childhood obesity

Background Primary prevention of childhood overweight is an international priority. In Australia 20-25% of 2-8 year olds are already overweight. These children are at substantially increased the risk of becoming overweight adults, with attendant increased risk of morbidity and mortality. Early feeding practices determine infant exposure to food (type, amount, frequency) and include responses (eg coercion) to infant feeding behaviour (eg. food refusal). There is correlational evidence linking parenting style and early feeding practices to child eating behaviour and weight status. A focus on early feeding is consistent with the national focus on early childhood as the foundation for life-long health and well being. The NOURISH trial aims to implement and evaluate a community-based intervention to promote early feeding practices that will foster healthy food preferences and intake and preserve the innate capacity to self-regulate food intake in young children. Methods/Design This randomised controlled trial (RCT) aims to recruit 820 first-time mothers and their healthy term infants. A consecutive sample of eligible mothers will be approached postnatally at major maternity hospitals in Brisbane and Adelaide. Initial consent will be for re-contact for full enrolment when the infants are 4-7 months old. Individual mother- infant dyads will be randomised to usual care or the intervention. The intervention will provide anticipatory guidance via two modules of six fortnightly parent education and peer support group sessions, each followed by six months of regular maintenance contact. The modules will commence when the infants are aged 4-7 and 13-16 months to coincide with establishment of solid feeding, and autonomy and independence, respectively. Outcome measures will be assessed at baseline, with follow up at nine and 18 months. These will include infant intake (type and amount of foods), food preferences, feeding behaviour and growth and self-reported maternal feeding practices and parenting practices and efficacy. Covariates will include sociodemographics, infant feeding mode and temperament, maternal weight status and weight concern and child care exposure. Discussion Despite the strong rationale to focus on parents’ early feeding practices as a key determinant of child food preferences, intake and self-regulatory capacity, prospective longitudinal and intervention studies are rare. This trial will be amongst to provide Level II evidence regarding the impact of an intervention (commencing prior to age 12 months) on children’s eating patterns and behaviours. Trial Registration: ACTRN12608000056392

My place through my eyes : a social constructionist approach to researching the relationships between socioeconomic living contexts and physical activity

There is a growing evidence-base in the epidemiological literature that demonstrates significant associations between people’s living circumstances – including their place of residence – and their health-related practices and outcomes (Leslie, 2005; Karpati, Bassett, & McCord, 2006; Monden, Van Lenthe, & Mackenbach, 2006; Parkes & Kearns, 2006; Cummins, Curtis, Diez-Roux, & Macintyre, 2007; Turrell, Kavanagh, Draper, & Subramanian, 2007). However, these findings raise questions about the ways in which living places, such as households and neighbourhoods, figure in the pathways connecting people and health (Frolich, Potvin, Chabot, & Corin, 2002; Giles-Corti, 2006; Brown et al, 2006; Diez Roux, 2007). This thesis addressed these questions via a mixed methods investigation of the patterns and processes connecting people, place, and their propensity to be physically active. Specifically, the research in this thesis examines a group of lower-socioeconomic residents who had recently relocated from poorer suburbs to a new urban village with a range of health-related resources. Importantly, the study contrasts their historical relationship with physical activity with their reactions to, and everyday practices in, a new urban setting designed to encourage pedestrian mobility and autonomy. The study applies a phenomenological approach to understanding living contexts based on Berger and Luckman’s (1966) conceptual framework in The Social Construction of Reality. This framework enables a questioning of the concept of context itself, and a treatment of it beyond environmental factors to the processes via which experiences and interactions are made meaningful. This approach makes reference to people’s histories, habituations, and dispositions in an exploration between social contexts and human behaviour. This framework for thinking about context is used to generate an empirical focus on the ways in which this residential group interacts with various living contexts over time to create a particular construction of physical activity in their lives. A methodological approach suited to this thinking was found in Charmaz’s (1996; 2001; 2006) adoption of a social constructionist approach to grounded theory. This approach enabled a focus on people’s own constructions and versions of their experiences through a rigorous inductive method, which provided a systematic strategy for identifying patterns in the data. The findings of the study point to factors such as ‘childhood abuse and neglect’, ‘early homelessness’, ‘fear and mistrust’, ‘staying indoors and keeping to yourself’, ‘conflict and violence’, and ‘feeling fat and ugly’ as contributors to an ongoing core category of ‘identity management’, which mediates the relationship between participants’ living contexts and their physical activity levels. It identifies barriers at the individual, neighbourhood, and broader ecological levels that prevent this residential group from being more physically active, and which contribute to the ways in which they think about, or conceptualise, this health-related behaviour in relationship to their identity and sense of place – both geographic and societal. The challenges of living well and staying active in poorer neighbourhoods and in places where poverty is concentrated were highlighted in detail by participants. Participants’ reactions to the new urban neighbourhood, and the depth of their engagement with the resources present, are revealed in the context of their previous life-experiences with both living places and physical activity. Moreover, an understanding of context as participants’ psychological constructions of various social and living situations based on prior experience, attitudes, and beliefs was formulated with implications for how the relationship between socioeconomic contextual effects on health are studied in the future. More detailed findings are presented in three published papers with implications for health promotion, urban design, and health inequalities research. This thesis makes a substantive, conceptual, and methodological contribution to future research efforts interested in how physical activity is conceptualised and constructed within lower socioeconomic living contexts, and why this is. The data that was collected and analysed for this PhD generates knowledge about the psychosocial processes and mechanisms behind the patterns observed in epidemiological research regarding socioeconomic health inequalities. Further, it highlights the ways in which lower socioeconomic living contexts tend to shape dispositions, attitudes, and lifestyles, ultimately resulting in worse health and life chances for those who occupy them.

Ethnic differences in body composition and anthropometric characteristics in Australian Caucasian and urban Indigenous children

The objective was to compare ethnic differences in anthropometry, including size, proportions and fat distribution, and body composition in a cohort of seventy Caucasian (forty-four boys, twenty-six girls) and seventy-four urban Indigenous (thirty-six boys, thirty-eight girls) children (aged 9–15 years). Anthropometric measures (stature, body mass, eight skinfolds, thirteen girths, six bone lengths and five bone breadths) and body composition assessment using dual-energy X-ray absorptiometry were conducted. Body composition variables including total body fat percentage and percentage abdominal fat were determined and together with anthropometric indices, including BMI (kg/m2), abdominal:height ratio (AHtR) and sum of skinfolds, ethnic differences were compared for each sex. After adjustment for age, Indigenous girls showed significantly (P < 0·05) greater trunk circumferences and proportion of overweight and obesity than their Caucasian counterparts. In addition, Indigenous children had a significantly greater proportion (P < 0·05) of trunk fat. The best model for total and android fat prediction included sum of skinfolds and age in both sexes (>93 % of variation). Ethnicity was only important in girls where abdominal circumference and AHtR were included and Indigenous girls showed significantly (P < 0·05) smaller total/android fat deposition than Caucasian girls at the given abdominal circumference or AHtR values. Differences in anthropometric and fat distribution patterns in Caucasian and Indigenous children may justify the need for more appropriate screening criteria for obesity in Australian children relevant to ethnic origin.