Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse.

RATIONALE: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). METHODS AND RESULTS: In vivo muscle glucose and intermediary metabolism was investigated following oral administration of [U-(13)C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring (13)C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography-mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. CONCLUSIONS: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle.

Specific role of dietary fat in modifying cardiovascular and locomotor activity 24-h rhythms

Meal-fed conscious rabbits normally exhibit postprandial elevation in blood pressure, heart rate (HR) and locomotor activity, which is abolished by consumption of a high-fat diet (HFD). Here, we assessed whether the cardiovascular changes are attributable to the increased caloric intake due to greater fat content or to hyperphagia. Rabbits were meal-fed during the baseline period then maintained on either an ad libitum normal fat diet (NFD) or ad libitum HFD for 2 weeks. Blood pressure, HR and locomotor activity were measured daily by radio-telemetry alongside food intake and body weight. Caloric intake in rabbits given a NFD ad libitum rose 50% from baseline but there were no changes in cardiovascular parameters. By contrast, HR increased by 10% on the first day of the ad libitum HFD (p<0.001) prior to any change in body weight while blood pressure increased 7% after 4d (p<0.01) and remained elevated. Baseline 24-h patterns of blood pressure and HR were closely associated with mealtime, characterised by afternoon peaks and morning troughs. When the NFD was changed from meal-fed to ad libitum, blood pressure and HR did not change but afternoon activity levels decreased (p<0.05). By contrast, after 13d ad libitum HFD, morning HR, blood pressure and activity increased by 20%, 8% and 71%, respectively. Increased caloric intake specifically from fat, but not as a result of hyperphagia, appears to directly modulate cardiovascular homeostasis and circadian patterns, independent of white adipose tissue accumulation.

In vivo cardiac glucose metabolism in the high-fat fed mouse: comparison of euglycemic-hyperinsulinemic clamp derived measures of glucose uptake with a dynamic metabolomic flux profiling approach

Rationale Cardiac metabolism is thought to be altered in insulin resistance and type 2 diabetes (T2D). Our understanding of the regulation of cardiac substrate metabolism and insulin sensitivity has largely been derived from ex vivo preparations which are not subject to the same metabolic regulation as in the intact heart in vivo. Studies are therefore required to examine in vivo cardiac glucose metabolism under physiologically relevant conditions. Objective To determine the temporal pattern of the development of cardiac insulin resistance and to compare with dynamic approaches to interrogate cardiac glucose and intermediary metabolism in vivo. Methods and results Studies were conducted to determine the evolution of cardiac insulin resistance in C57Bl/6 mice fed a high-fat diet (HFD) for between 1 and 16 weeks. Dynamic in vivo cardiac glucose metabolism was determined following oral administration of [U-¹³C] glucose. Hearts were collected after 15 and 60 min and flux profiling was determined by measuring ¹³C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates. Cardiac insulin resistance, determined by euglycemic-hyperinsulinemic clamp, was evident after 3 weeks of HFD. Despite the presence of insulin resistance, in vivo cardiac glucose metabolism following oral glucose administration was not compromised in HFD mice. This contrasts our recent findings in skeletal muscle, where TCA cycle activity was reduced in mice fed a HFD. Similar to our report in muscle, glucose derived pyruvate entry into the TCA cycle in the heart was almost exclusively via pyruvate dehydrogenase, with pyruvate carboxylase mediated anaplerosis being negligible after oral glucose administration. Conclusions Under experimental conditions which closely mimic the postprandial state, the insulin resistant mouse heart retains the ability to stimulate glucose metabolism.

Inulin and maltodextrin can replace fat in baked savoury legume snacks

A baked yellow split pea cracker was developed with fat replacement (0%, 25%, 50%, 75% and 100%) using inulin, hydroxypropyl methylcellulose and maltodextrin. Effects of fat replacement on physical (water activity, moisture content, colour and hardness), nutritional properties and consumer acceptance (nine-point hedonic rating) of snacks were investigated. Water activity (0.15-0.32) and moisture (1.28-3.16%) readings were consistent, and products were considered shelf stable. High levels of fat replacement (100%) were detrimental to snack colour and hardness. Snacks with 75% fat replacement using inulin and maltodextrin received similar mean overall acceptability scores (6.40 ± 1.36 and 6.26 ± 1.37, respectively) to the control and a similar commercial product. These snacks were eligible to claim that they were a 'good source' of protein (requirement; ≥10 g per serve) and an 'excellent source' of dietary fibre (requirement; ≥7 g per serve) while providing 'reduced' fat content (≤25% than reference food) based on the Australian Food Standards Code.

Resistive exercises, with or without whole body vibration, prevent vertebral marrow fat accumulation during 60 days of head-down tilt bed rest in men

Fat accumulates in the bone marrow of lumbar vertebrae with bed rest. Exercise with or without whole body vibration may counter this effect. Our objectives were to measure 1) the vertebral fat fraction (VFF) of men subjected to bed rest who performed resistive exercises with (RVE, n = 7) or without whole body vibration(RE, n = 8) or no exercise (CTR, n = 9) using three MRI techniques; and 2) changes in peripheral blood counts. Twenty-four healthy men (age: 20-45 yr) underwent -6° head-down tilt (HDT) bed rest for 60 days. MRI was performed using three techniques (fat saturation, proton spectroscopy, and in and out of phase) to measure the fat fraction of L(3), L(4), and/or L(5) at baseline, mid-HDT, and end-HDT. Erythrocytes and leukocytes were counted at HDT days 19, 33, 47, 54, and 60. The mean absolute VFF was increased in the CTR group at mid-HDT and end-HDT (+3.9 ± 1.3 and +3.6 ± 1.2%, respectively, both P < 0.05). The RE group had a smaller VFF change than the CTR group at mid-HDT (-0.9 ± 1.2 vs. +3.9 ± 1.3%, P < 0.05). The RVE group had a smaller VFF change than the CTR group at end-HDT (-2.6 ± 1.9 vs. +3.5 ± 1.2%, P < 0.05). Erythrocyte counts were increased in all groups at HDT day 19 and HDT day 33 and in the RE group at HDT day 54 (all P < 0.05). Bed rest for 60 days at -6° HDT increased lumbar VFF in men beyond natural involution. RVE and RE regimens effectively prevented VFF accumulation. Higher erythrocyte counts were not altered by RVE or RE. Whole body vibration, along with RE administered to people with prolonged immobility, may prevent fat accumulation in their bone marrow.

Don't eat that, you'll get fat! Exploring how parents and children conceptualise and frame messages about the causes and consequences of obesity

Family interactions about weight and health take place against the backdrop of the wider social discourse relating to the obesity epidemic. Parents (and children) negotiate complex and often contradictory messages in constructing a set of beliefs and practices around obesity and weight management. Despite this, very little research attention has been given to the nature of family-unit discourse on the subject of body weight and it's potential influence on the weight-related behaviours of family members. This includes the broad influence that dominant socio-cultural discourses have on family conceptualisations of weight and health. Using in-depth qualitative interviews with 150 family 'groups' comprised of at least one parent and one child in Victoria and South Australia, we explored how parents and children conceptualise and discuss issues of weight- and health-related lifestyle behaviours. Data were analysed using Attride-Stirling's (2001) thematic network approach. Three thematic clusters emerged from the analysis. First, both parents and children perceived that weight was the primary indicator of health. However, parents focused on the negative physical implications of overweight while children focused on the negative social implications. Second, weight and lifestyle choices were highly moralised. Parents saw it as their responsibility to communicate to children the 'dangers' of fatness. Children reported that parents typically used negatively-framed messages and scare tactics rather than positively-framed messages to encourage healthy behaviours. Third was the perception among parents and children that if you were thin, then eating habits and exercise were less important, and that activity could provide an antidote to food choices. Results suggest that both parents and children are internalising messages relating to obesity and weight management that focus on personal responsibility and blame attribution. These views reflect the broader societal discourse, and their consolidation at the family level is likely to increase their potency and make them resistant to change.

I'm searching for solutions: why are obese individuals turning to the Internet for help and support with 'being fat'?

INTRODUCTION: This study explores what types of information obese individuals search for on the Internet, their motivations for seeking information and how they apply it in their daily lives. METHOD: In-depth telephone interviews with an Australian community sample of 142 individuals with a BMI ≥ 30 were conducted. Theoretical, purposive and strategic samplings were employed. Data were analysed using a constant comparative method. RESULTS: Of the 142 individuals who participated in the study, 111 (78%) searched for information about weight loss or obesity. Of these, about three quarters searched for weight loss solutions. The higher the individual's weight, the more they appeared to search for weight loss solutions. Participants also searched for information about health risks associated with obesity (n = 28), how to prevent poor health outcomes (n = 30) and for peer support forums with other obese individuals (n = 25). Whilst participants visited a range of websites, including government-sponsored sites, community groups and weight loss companies, they overwhelmingly acted upon the advice given on commercial diet websites. However, safe, non-judgemental spaces such as the Fatosphere (online fat acceptance community) provided much needed solidarity and support. CONCLUSIONS: The Internet provides a convenient source of support and information for obese individuals. However, many turn to the same unsuccessful solutions online (e.g. fad dieting) they turn to in the community. Government and community organisations could draw upon some lessons learned in other consumer-driven online spaces (e.g. the Fatosphere) to provide supportive environments for obese individuals that resonate with their health and social experiences, and address their needs.

The role of the fatosphere in fat adults' responses to obesity stigma: a model of empowerment without a focus on weight loss

Obese adults face pervasive and repeated weight-based stigma. Few researchers have explored how obese individuals proactively respond to stigma outside of a dominant weight-loss framework. Using a grounded theory approach, we explored the experiences of 44 bloggers within the Fatosphere--an online fat-acceptance community. We investigated participants' pathways into the Fatosphere, how they responded to and interacted with stigma, and how they described the impact of fat acceptance on their health and well-being. The concepts and support associated with the fat-acceptance movement helped participants shift from reactive strategies in responding to stigma (conforming to dominant discourses through weight loss) to proactive responses to resist stigma (reframing "fat" and self-acceptance). Participants perceived that blogging within the Fatosphere led them to feel more empowered. Participants also described the benefits of belonging to a supportive community, and improvements in their health and well-being. The Fatosphere provides an alternative pathway for obese individuals to counter and cope with weight-based stigma.

Challenging stereotypes and legitimating fat: an analysis of obese people's views on news media reporting guidelines and promoting body diversity

© The Author(s) 2013. This article contributes to scholarship on the cultural politics of obesity by providing insights into how people considered ‘obese’ think news media reporting should be improved and their views on ideas such as reporting guidelines and promoting body diversity. A thematic analysis of interview data identified the following themes: ‘Challenging stereotypes’, ‘The limits of news’, ‘Individual responsibility’ and ‘Legitimating fat’. These themes capture the divergence in views and reflect differences in how people construct obesity and conceive the influences of media on audiences. Situated in the context of the contested science and news frames surrounding obesity, the analysis also engages with wider debates about the potentially unintended consequences of seeking to challenge stigma. We conclude that media and policy discourses need to reflect a diversity of ways of framing obesity if the views of obese people are to be included.

Our girth is plain to see: an analysis of newspaper coverage of Australia's future 'fat bomb'

The news media plays an important role in making visible and shaping public understandings of health and health risks. In relation to overweight and obesity, it has been suggested that the media is more likely to engage in alarmist reporting in a climate in which it is taken for granted that obesity is an 'epidemic'. This study analyses Australian media coverage of a report on overweight and obesity, Australia's Future 'Fat Bomb': a report on the long-term consequences of Australia's expanding waistline on cardiovascular disease, by one of Australia's leading health and medical research institutes. Our study found that the report was consistently framed across media outlets as showing that Australia is the 'fattest nation' in the world, having overtaken the Americans. This is despite the fact that the Fat Bomb study did not include international comparisons and was based only on data from middle-aged Australians. Because reports of increasing rates of obesity had already been widely covered in the media, the press needed to find a new way of signifying the problem, which was provided by comments made by its lead author in publicising the report. Consistent with previous research, there was a notable absence of critical commentary on the study and a failure to test the claims of its lead author. We conclude that this reporting could have contributed to a policy environment in which the perceived threat of obesity is deemed to be so great that efforts to contain it may be subjected to less scrutiny than they warrant. © 2011 Taylor & Francis.

Marginal efficiencies of long chain-polyunsaturated fatty acid use by barramundi (Lates calcarifer) when fed diets with varying blends of fish oil and poultry fat

An experiment was conducted with barramundi (Lates calcarifer) juveniles to examine the marginal efficiency of utilisation of long chain-polyunsaturated fatty acids (LC-PUFA). A series of five diets with blends of fish (anchovy) oil and poultry fat (F100:P0, F60:P40, F30:P70, F15:P85, F0:P100) were fed to 208. ±. 4.1. g fish over a 12-week period. The replacement of fish oil with poultry fat had no impact on growth performance (average final weight of 548.3. ±. 10.2. g) or feed conversion (mean = 1.14. ±. 0.02). Analysis of the whole body composition showed that the fatty acid profile reflected that of the fed diet. However it was also shown that there was a disproportional retention of some fatty acids relative to others (notably LOA, 18:2n-6 and LNA, 18:3n-3). By examining the body mass independent retention of different fatty acids with differential levels of intake of each, the marginal efficiencies of the use of these nutrients by this species were able to be determined. The differential retention of fatty acids in the meat was also examined allowing the determination of oil blending strategies to optimise meat n-3 LC-PUFA levels.

Sex, fat and the tilt of the earth: effects of sex and season on the feeding response to centrally administered leptin in sheep

Whilst there have been many studies in various species examining the effects of leptin on food intake, there is a paucity of data comparing responsiveness in the two sexes. We have, therefore, addressed this issue in sheep. Because this species shows seasonal variation in voluntary food intake (VFI), we also considered the possibility that there might be seasonal variation in the responsivity to leptin. Centrally administered leptin was relatively ineffective as a satiety factor in either sex during AUTUMN: In Spring, leptin had a profound inhibitory effect on VFI in the females, but only a slight effect in males. These data indicate that responsiveness to leptin depends on sex and also on season in animals that are substantially affected by photoperiod.

PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation.