The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes that reflect dietary intakes and fecal water content.

Obesity is a complex, multifactorial condition that is an important risk factor for noncommunicable diseases including cardiovascular disease and type 2 diabetes. While prevention and management require a healthy and energy balanced diet and adequate physical activity, the taxonomic composition and functional attributes of the colonic microbiota may have a supplementary role in the development of obesity. The taxonomic composition and metabolic capacity of the fecal microbiota of 286 women, resident in Auckland New Zealand, was determined by metagenomic analysis. Associations with BMI (obese, nonobese), body fat composition, and ethnicity (Pacific, n = 125; NZ European women [NZE], n = 161) were assessed using regression analyses. The fecal microbiotas were characterized by the presence of three distinctive enterotypes, with enterotype 1 represented in both Pacific and NZE women (39 and 61%, respectively), enterotype 2 mainly in Pacific women (84 and 16%) and enterotype 3 mainly in NZE women (13 and 87%). Enterotype 1 was characterized mainly by the relative abundances of butyrate producing species, Eubacterium rectale and Faecalibacterium prausnitzii, enterotype 2 by the relative abundances of lactic acid producing species, Bifidobacterium adolescentis, Bifidobacterium bifidum, and Lactobacillus ruminis, and enterotype 3 by the relative abundances of Subdoligranulum sp., Akkermansia muciniphila, Ruminococcus bromii, and Methanobrevibacter smithii. Enterotypes were also associated with BMI, visceral fat %, and blood cholesterol. Habitual food group intake was estimated using a 5 day nonconsecutive estimated food record and a 30 day, 220 item semi-quantitative Food Frequency Questionnaire. Higher intake of 'egg' and 'dairy' products was associated with enterotype 3, whereas 'non-starchy vegetables', 'nuts and seeds' and 'plant-based fats' were positively associated with enterotype 1. In contrast, these same food groups were inversely associated with enterotype 2. Fecal water content, as a proxy for stool consistency/colonic transit time, was associated with microbiota taxonomic composition and gene pools reflective of particular bacterial biochemical pathways. The fecal microbiotas of women of Pacific and New Zealand European ethnicities are characterized by distinctive enterotypes, most likely due to differential dietary intake and fecal consistency/colonic transit time. These parameters need to be considered in future analyses of human fecal microbiotas.

Outcomes of a culturally informed weight-loss competition for New Zealand Indigenous and Pacific peoples: a quasi-experimental trial.

BACKGROUND: Reducing obesity prevalence among marginalised subgroups with disproportionately high obesity rates is challenging. Given the promise of incentives and group-based programmes we trialled a culturally tailored, team-based weight-loss competition with New Zealand Maori (Indigenous) and Pacific Island people. METHODS: A quasi-experimental 12-months trial was designed. The intervention consisted of three six-months competitions, each with seven teams of seven members. Eligible participants were aged 16 years and older, with a BMI ≥30 kg/m2 and being at risk of or already diagnosed with type-2 diabetes or cardiovascular disease. Height, weight and waist circumference were measured at baseline, 6 and 12 months. RESULTS: Recruitment of a control group (n = 29) versus the intervention (n = 132) was poor and retention rates were low (52 and 27% of intervention participants were followed-up at six and 12 months, respectively). Thus, analysis of the primary outcome of individual percentage weight loss was restricted to the 6-months follow-up data. Although not significant, the intervention group appeared to lose more weight than the control group, in both the intention to treat and complete-case analyses. CONCLUSIONS: The intervention promoted some behaviour change in eating behaviours, and a resulting trend toward a reduction in waist circumference. TRIAL REGISTRATION: ACTRN12617000871347 Registered 15/6/2017 Retrospectively registered.

Objectively Measured Physical Activity Is Associated With Body Composition and Metabolic Profiles of Pacific and New Zealand European Women With Different Metabolic Disease Risks.

Objective: To assess associations between physical activity (PA), body composition, and biomarkers of metabolic health in Pacific and New Zealand European (NZE) women who are known to have different metabolic disease risks. Methods: Pacific (n = 142) or NZE (n = 162) women aged 18-45 years with a self-reported body mass index (BMI) of either 18.5-25.0 kg⋅m-2 or ≥30.0 kg⋅m-2 were recruited and subsequently stratified as either low (<35%) or high (≥35%) BF%, with approximately half of each group in either category. Seven-day accelerometery was used to assess PA levels. Fasting blood was analysed for biomarkers of metabolic health, and whole body dual-energy X-ray absorptiometry (DXA) was used to estimate body composition. Results: Mean moderate-to-vigorous physical activity (MVPA; min⋅day-1) levels differed between BF% (p < 0.05) and ethnic (p < 0.05) groups: Pacific high- 19.1 (SD 15.2) and low-BF% 26.3 (SD 15.6) and NZE high- 30.5 (SD 19.1) and low-BF% 39.1 (SD 18.4). On average Pacific women in the low-BF% group engaged in significantly less total PA when compared to NZE women in the low-BF% group (133 cpm); no ethnic difference in mean total PA (cpm) between high-BF% groups were observed: Pacific high- 607 (SD 185) and low-BF% 598 (SD 168) and NZE high- 674 (SD 210) and low-BF% 731 (SD 179). Multiple linear regression analysis controlling for age and deprivation showed a significant inverse association between increasing total PA and fasting plasma insulin among Pacific women; every 100 cpm increase in total PA was associated with a 6% lower fasting plasma insulin; no significant association was observed in NZE women. For both Pacific and NZE women, there was an 8% reduction in fasting plasma insulin for every 10-min increase in MVPA (p ≤ 0.05). Conclusion: Increases in total PA and MVPA are associated with lower fasting plasma insulin, thus indicating a reduction in metabolic disease risk. Importantly, compared to NZE, the impact of increased total PA on fasting insulin may be greater in Pacific women. Considering Pacific women are a high metabolic disease risk population, these pre-clinical responses to PA may be important in this population; indicating promotion of PA in Pacific women should remain a priority.

Predictors Linking Obesity and the Gut Microbiome (the PROMISE Study): Protocol and Recruitment Strategy for a Cross-Sectional Study on Pathways That Affect the Gut Microbiome and Its Impact on Obesity.

BACKGROUND: The prevalence of obesity has increased substantially over recent decades and is associated with considerable health inequalities. Although the causes of obesity are complex, key drivers include overconsumption of highly palatable, energy-dense, and nutrient-poor foods, which have a profound impact on the composition and function of the gut microbiome. Alterations to the microbiome may play a critical role in obesity by affecting energy extraction from food and subsequent energy metabolism and fat storage. OBJECTIVE: We report the study protocol and recruitment strategy of the PRedictors linking Obesity and the gut MIcrobiomE (PROMISE) study, which characterizes the gut microbiome in 2 populations with different metabolic disease risk (Pacific and European women) and different body fat profiles (normal and obese). It investigates (1) the role of gut microbiome composition and functionality in obesity and (2) the interactions between dietary intake; eating behavior; sweet, fat, and bitter taste perception; and sleep and physical activity; and their impact on the gut microbiome, metabolic and endocrine regulation, and body fat profiles. METHODS: Healthy Pacific and New Zealand (NZ) European women aged between 18 and 45 years from the Auckland region were recruited for this cross-sectional study. Participants were recruited such that half in each group had either a normal weight (body mass index [BMI] 18.5-24.9 kg/m2) or were obese (BMI ≥30.0 kg/m2). In addition to anthropometric measurements and assessment of the body fat content using dual-energy x-ray absorptiometry, participants completed sweet, fat, and bitter taste perception tests; food records; and sleep diaries; and they wore accelerometers to assess physical activity and sleep. Fasting blood samples were analyzed for metabolic and endocrine biomarkers and DNA extracted from fecal samples was analyzed by shotgun sequencing. Participants completed questionnaires on dietary intake, eating behavior, sleep, and physical activity. Data were analyzed using descriptive and multivariate regression methods to assess the associations between dietary intake, taste perception, sleep, physical activity, gut microbiome complexity and functionality, and host metabolic and body fat profiles. RESULTS: Of the initial 351 women enrolled, 142 Pacific women and 162 NZ European women completed the study protocol. A partnership with a Pacific primary health and social services provider facilitated the recruitment of Pacific women, involving direct contact methods and networking within the Pacific communities. NZ European women were primarily recruited through Web-based methods and special interest Facebook pages. CONCLUSIONS: This cross-sectional study will provide a wealth of data enabling the identification of distinct roles for diet, taste perception, sleep, and physical activity in women with different body fat profiles in modifying the gut microbiome and its impact on obesity and metabolic health. It will advance our understanding of the etiology of obesity and guide future intervention studies involving specific dietary approaches and microbiota-based therapies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000432213; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370874. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/14529.

Dietary Patterns in New Zealand Women: Evaluating Differences in Body Composition and Metabolic Biomarkers.

The combinations of food consumed together (dietary patterns) may have a greater influence on health than nutrients or food groups consumed independently. This study investigated the relationship between dietary patterns, body composition and metabolic biomarkers of premenopausal New Zealand women from three ethnic groups. In total, 408 New Zealand European, Maori and Pacific women aged 16-45 years participated in the Women's EXPLORE (EXamining Predictors Linking Obesity Related Elements) study. Participants completed a 220-item food frequency questionnaire. Several body composition parameters and metabolic biomarkers were measured. Dietary patterns were extracted by principal component analysis and dietary pattern scores were categorised into tertiles to assess links with other measured parameters. Women with higher scores for the 'refined and processed' pattern were younger, had higher body mass index, total body fat, plasma leptin and plasma insulin (p < 0.001), and lower plasma ghrelin levels (p < 0.05) than women with lower scores. In addition, more Maori (51%) and Pacific (68%) women followed the 'refined and processed' pattern, while more New Zealand European women (40%) followed the 'sweet and savoury snacking' pattern. These data show that dietary pattern analysis is a useful tool to assess links between diet and metabolic health. It further reveals interesting ethnic group-specific differences in dietary pattern use.

Adherence to daily dietary and activity goals set within a Maori and Pacific weight loss competition.

BACKGROUND: New Zealand Pacific and Maori populations measure disproportionately high on the international body mass index (BMI). Information is needed on what behavioural weight loss goals to recommend and how to attract and retain them in interventions. Our team weight loss competition trial for participants with a BMI ≥30 used cash prizes to incentivise completion of nine daily behaviour goals. This paper evaluates the theoretical merit of and adherence to these goals. METHODS: A qualitative component evaluation methodology was used. Trial data on team activity, demographics and anthropometric outcome data were extracted to determine frequency of daily goal completion by teams throughout the competition and to describe participant characteristics. T-tests were used to compare completion rates of the challenges, challenge completion by day of week and between weekdays and weekends. To examine adherence to the daily challenge activity over 24 weeks the total amount of completed challenges adjusted for number of active teams was plotted by week. A Body Shape Index (ABSI) was used to determine individual anthropometric change from baseline to 8, 16 and 24 weeks. Program documents were analysed to identify barriers to adherence and retention of participants. RESULTS: Of 19 teams (N = 130) who began only five teams performed daily goals across the whole 24 weeks. Adherence was highest during the first 8 weeks. No difference in performance between goals was found suggesting they were equally viable, though tasks worth less points were performed more frequently. Goal completion was higher on weekdays. The behaviour goals appeared to have theoretical merit in that more members of high performing teams experienced a positive change in their ABSI. CONCLUSIONS: Incentives offer a promising strategy for encouraging retention in weight loss interventions. This study suggests that participants in a competition will perform incentivised tasks. The findings however, are limited by missing data and high drop out of individuals and whole teams. Further research is needed on how to increase retention.

Fat Sensation: Fatty Acid Taste and Olfaction Sensitivity and the Link with Disinhibited Eating Behaviour.

Perception of fat taste, aroma, and texture are proposed to influence food preferences, thus shaping dietary intake and eating behaviour and consequently long-term health. In this study, we investigated associations between fatty acid taste, olfaction, mouthfeel of fat, dietary intake, eating behaviour, and body mass index (BMI). Fifty women attended three sessions to assess oleic acid taste and olfaction thresholds, the olfactory threshold for n-butanol and subjective mouthfeel ratings of custard samples. Dietary intake and eating behaviour were evaluated using a Food Frequency and Three-Factor Eating Questionnaire, respectively. Binomial regression analysis was used to model fat taste and olfaction data. Taste and olfactory detection for oleic acid were positively correlated (r = 0.325; p < 0.02). Oleic acid taste hypersensitive women had significantly increased n-butanol olfactory sensitivity (p < 0.03). The eating behaviour disinhibition and BMI were higher in women who were hyposensitive to oleic acid taste (p < 0.05). Dietary intake of nuts, nut spreads, and seeds were significantly correlated with high olfactory sensitivity to oleic acid (p < 0.01). These findings demonstrate a clear link between fatty acid taste sensitivity and olfaction and suggest that fat taste perception is associated with specific characteristics of eating behaviour and body composition.

Is Sweet Taste Perception Associated with Sweet Food Liking and Intake?

A range of psychophysical taste measurements are used to characterize an individual's sweet taste perception and to assess links between taste perception and dietary intake. The aims of this study were to investigate the relationship between four different psychophysical measurements of sweet taste perception, and to explore which measures of sweet taste perception relate to sweet food intake. Forty-four women aged 20-40 years were recruited for the study. Four measures of sweet taste perception (detection and recognition thresholds, and sweet taste intensity and hedonic liking of suprathreshold concentrations) were assessed using glucose as the tastant. Dietary measurements included a four-day weighed food record, a sweet food-food frequency questionnaire and a sweet beverage liking questionnaire. Glucose detection and recognition thresholds showed no correlation with suprathreshold taste measurements or any dietary intake measurement. Importantly, sweet taste intensity correlated negatively with total energy and carbohydrate (starch, total sugar, fructose, glucose) intakes, frequency of sweet food intake and sweet beverage liking. Furthermore, sweet hedonic liking correlated positively with total energy and carbohydrate (total sugar, fructose, glucose) intakes. The present study shows a clear link between sweet taste intensity and hedonic liking with sweet food liking, and total energy, carbohydrate and sugar intake.

Exploring the challenges in obtaining physical activity data from women using hip-worn accelerometers.

Quality objective physical activity data are required to inform physical activity-based health improvement initiatives, however, various challenges undermine acquisition of such data. We examined the efficacy and challenges of a hip-worn accelerometry protocol in women. Specific objectives included determining accelerometer-wear-compliance rates and understanding the barriers and acceptability of wearing accelerometers. Healthy New Zealand women (n = 406) of three ethnicities (Maori (indigenous New Zealander), Pacific, European) aged 16-45 years (30.9 ± 8.7 y) wore hip-mounted Actigraph wGT3X+ accelerometers for 7 consecutive days under a 24-h wear protocol. Post hoc, a sub-sample (n = 45; age: 29.4 ± 9.0 y) was interviewed to investigate comfort/convenience and burdens of accelerometer-wear. Wear-compliance (≥10 h/day, ≥4 day) was 86%. European women returned more valid data (92.7%, p < .04) than Pacific (73.0%) or Maori women (82.1%). Twenty-two participants (5.4%) had completely missing data; 13 due to lost accelerometers. Burden of accelerometer-wear was greatest during sleeping (66.7%) due to discomfort. Embarrassment of accelerometer visibility through clothing and consequent restricted clothing choices caused high burden in social settings (45.2%). Discomfort during sleeping, embarrassment due to perceived appearance in social settings and ethnicity are key factors affecting the efficacy of collecting physical activity data from women using hip-worn accelerometers. Refining accelerometer design to reduce size and subsequently participant burden should improve acceptability and wear-compliance. Increasing overall participant compliance by reducing burden and ensuring appropriate understanding of study aims and relevance should reduce attrition and improve wear-compliance and data quality when collecting accelerometry data from women of different ethnicities.

Effect of mouth rinsing and ingestion of carbohydrate solutions on mood and perceptual responses during exercise.

BACKGROUND: The aim of this study was to investigate whether mouth rinsing or ingesting carbohydrate (CHO) solutions impact on perceptual responses during exercise. METHODS: Nine moderately trained male cyclists underwent a 90-min glycogen-reducing exercise, and consumed a low CHO meal, prior to completing an overnight fast. A 1-h cycle time trial was performed the following morning. Four trials, each separated by 7 days, were conducted in a randomized, counterbalanced study design: 15% CHO mouth rinse (CHOR), 7.5% CHO ingestion (CHOI), placebo mouth rinse (PLAR) and placebo ingestion (PLAI). Solution volumes (1.5 ml · kg-1 ingestion trials and 0.33 ml · kg-1 rinsing trials) were provided after every 12.5% of completed exercise. Perceptual scales were used to assess affective valence (feeling scale, FS), arousal (felt arousal scale, FAS), exertion (ratings of perceived exertion, RPE) and mood (profile of mood states, POMS) before, during and immediately after exercise. RESULTS: There was no difference in RPE (CHOI, 14.0 ± 1.9; CHOR, 14.2 ± 1.7; PLAI, 14.6 ± 1.8; PLAR, 14.6 ± 2.0; P = 0.35), FS (CHOI, 0.0 ± 1.7; CHOR, -0.2 ± 1.5; PLAI, -0.8 ± 1.4; PLAR, -0.8 ± 1.6; P = 0.15), or FAS (CHOI, 3.6 ± 1.1; CHOR, 3.5 ± 1.0; PLAI, 3.4 ± 1.4; PLAR, 3.3 ± 1.3; P = 0.725) scores between trials. While overall POMS score did not appear to differ between trials, the 'vigour' subscale indicated that CHOI may facilitate the maintenance of 'vigour' scores over time, in comparison to the steady decline witnessed in other trials (P = 0.04). There was no difference in time trial performance between trials (CHOI, 65.3 ± 4.8 min; CHOR, 68.4 ± 3.9 min; PLAI, 68.7 ± 5.3 min; PLAR, 68.3 ± 5.2 min; P = 0.21) but power output was higher in CHOI (231.0 ± 33.2 W) relative to other trials (221-223.6 W; P < 0.01). CONCLUSIONS: In a CHO-reduced state, mouth rinsing with a CHO solution did not impact on perceptual responses during high-intensity exercise in trained cyclists and triathletes. On the other hand CHO ingestion improved perceived ratings of vigour and increased power output during exercise.

Could Vaping be a New Weapon in the Battle of the Bulge?

IMPLICATIONS: Obesity is set to overtake tobacco smoking in many countries as the primary cause of several high-cost diseases. Tobacco smoking mitigates weight gain through nicotine's effect on the brain and metabolism. Smoking, however, is associated with many illnesses and premature death and appropriately has been discouraged leading to declining prevalence rates. This article explores the emerging perception that vaping electronic cigarettes with nicotine and flavors could deliver similar appetite and weight control effects as smoking. The potential to reduce risks associated with excess weight deserves exploration. An initial research agenda is suggested.

An innovative team-based weightloss competition to reduce cardiovascular and diabetes risk among Maori and Pacific people: rationale and method for the study and its evaluation.

BACKGROUND: Obesity rates for New Zealand (NZ) Pacific and Maori (NZ indigenous people) are among the highest in the world. Long-term results of weight management programmes for adults have been modest but primarily focused on individuals. This paper describes the rationale and methodology for a trial of a culturally tailored team-based weightloss competition conducted online with community level support. METHODS/DESIGN: A quasi-experimental design was used to compare an intervention and control group. Three six-month competitions with seven teams of seven Maori or Pacific people (N = 147) were run. Eligible participants were: Maori or Pacific, 16 years of age and above, obese (BMI ≥30 kg/m2) and either at risk of or already diagnosed with type 2 diabetes (HbA1c >50 mmol/mol) or cardiovascular disease.The intervention facilitated group use of an internet-based competition offering financial incentives, education and support. The primary outcome was percentage of individual weight lost at 12-months. Secondary outcomes were percentage reduced total cholesterol and glycated haemoglobin (HbA1c). Data collected at baseline, 6-months and 12-months included: height, body weight, blood lipids and HbA1c, eating and dieting habits, family support, food access, alcohol use, nutrition literacy, activity levels, perceptions of weight, stress and sleep, and, perceived contagion effect. Process evaluation tasks will inform acceptability. DISCUSSION: An attractive, easy to understand weight change programme that effectively reduces disease risk among Maori and Pacific is desperately needed. Web-based delivered support and information to largely self-directed teams could also ease exponential rises in costs to the health system. TRIAL REGISTRATION: Trial Id: ACTRN12617000871347.

Carbohydrate mouth rinsing has no effect on power output during cycling in a glycogen-reduced state.

BACKGROUND: The effect of mouth rinsing with a carbohydrate (CHO) solution on exercise performance is inconclusive with no benefits observed in the fed state. This study examined the effect of CHO mouth rinse or CHO ingestion on performance in 9 moderately trained male cyclists. METHODS: Four trials were undertaken, separated by 7 days, in a randomized, counterbalanced design. Each trial included a 90-min glycogen-reducing exercise protocol, immediately followed by a low CHO meal and subsequent overnight fast; the following morning a 1-h cycling time trial was conducted. The trials included 15 % CHO mouth rinse (CHOR), 7.5 % CHO ingestion (CHOI), placebo mouth rinse and placebo ingestion. Solutions were provided after every 12.5 % of completed exercise: 1.5 mL · kg(-1) and 0.33 mL · kg(-1) body mass during ingestion and rinse trials, respectively. During rinse trials participants swirled the solution for 8 s before expectorating. Blood samples were taken at regular intervals before and during exercise. RESULTS: Performance time was not different between trials (P = 0.21) but the 4.5-5.2 % difference between CHOI and other trials showed moderate practical significance (Cohen's d 0.57-0.65). Power output was higher in CHOI relative to other trials (P < 0.01). There were no differences between CHOR and placebo groups for any performance variables. Plasma glucose, insulin and lactate concentrations were higher in CHOI relative to other groups (P < 0.05). CONCLUSIONS: In a fasted and glycogen-reduced state ingestion of a CHO solution during high-intensity exercise enhanced performance through stimulation of insulin-mediated glucose uptake. The CHO mouth rinsing had neither ergogenic effects nor changes in endocrine or metabolic responses relative to placebo.

Diet-induced obesity and prenatal undernutrition lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei.

Previously we reported that prenatal undernutrition (UN) leads to a dysregulation of appetite suppression through alterations in hypothalamic neuropeptide gene expression. In the current study, we expand our observations and investigate neuroendocrine transcriptional responses and central leptin sensitivity within the arcuate nucleus of rats exposed to prenatal UN or a postnatal high-fat diet (HF). Pregnant Wistar rats were fed a standard chow diet either ad libitum (AD) or at 30 % of AD intake throughout gestation (UN) resulting in either control or intrauterine growth-restricted female offspring. At weaning, AD offspring were fed either a chow (C) or a HF (30 % fat wt/wt) diet ad libitum for the remainder of the study, whereas UN offspring were fed a chow diet only. At ~142 days, AD and UN offspring received either recombinant rat leptin (L) or saline (S) subcutaneously for 14 days. Prenatal UN had a significant effect on hypothalamic NPY (P < 0.0001), AgRP (P < 0.01) and ObRb (P < 0.02) mRNA expression compared to AD chow-fed offspring. A postnatal HF diet had a significant effect on AgRP mRNA expression (P < 0.001), compared to AD chow-fed offspring, but no effect on NPY and ObRb expression. Leptin treatment, in both UN and HF offspring, was ineffective in reducing NPY and AgRP mRNA expression, and had no effect on ObRb expression. These findings suggest that prenatal UN and a postnatal HF diet lead to differential neuroendocrine gene expression in the hypothalamic arcuate nuclei and reduced sensitivity to leptin's anorexigenic effects.

Metabolic programming of adipose tissue structure and function in male rat offspring by prenatal undernutrition.

BACKGROUND: A number of different pathways to obesity with different metabolic outcomes are recognised. Prenatal undernutrition in rats leads to increased fat deposition in adulthood. However, the form of obesity is metabolically distinct from obesity induced through other pathways (e.g. diet-induced obesity). Previous rat studies have shown that maternal undernutrition during pregnancy led to insulin hyper-secretion and obesity in offspring, but not to systemic insulin resistance. Increased muscle and liver glycogen stores indicated that glucose is taken up efficiently, reflecting an active physiological function of these energy storage tissues. It is increasingly recognised that adipose tissue plays a central role in the regulation of metabolism and pathophysiology of obesity development. The present study investigated the cell size and endocrine responsiveness of subcutaneous and visceral adipose tissue from prenatally undernourished rats. We aimed to identify whether these adipose tissue depots contribute to the altered energy metabolism observed in these offspring. METHODS: Adipocyte size was measured in both subcutaneous (ScAT) and retroperitoneal adipose tissue (RpAT) in male prenatally ad libitum fed (AD) or prenatally undernourished (UN) rat offspring. Metabolic responses were investigated in adipose tissue explants stimulated by insulin and beta3 receptor agonists ex vivo. Expression of markers of insulin signalling was determined by Western blot analyses. Data were analysed by unpaired t-test or Two Way ANOVA followed by Fisher's PLSD post-hoc test, where appropriate. RESULTS: Adipocytes in offspring of undernourished mothers were larger, even at a lower body weight, in both RpAT and ScAT. The insulin response of adipose tissue was reduced in ScAT, and statistically absent in RpAT of UN rats compared with control. This lack of RpAT insulin response was associated with reduced expression of insulin signalling pathway proteins. Adrenergic receptor-driven lipolysis was observed in both adipose depots; however insulin failed to express its anti-lipolytic effect in RpAT in both, AD and UN offspring. CONCLUSIONS: Metabolic dysregulation in offspring of undernourished mothers is mediated by increased adipocyte size and reduced insulin responsiveness in both ScAT and especially in RpAT. These functional and morphological changes in adipocytes were accompanied by impaired activity of the insulin signalling cascade highlighting the important role of different adipose tissue depots in the pathogenesis of metabolic disorders.

Postnatal development of metabolic flexibility and enhanced oxidative capacity after prenatal undernutrition.

Metabolic flexibility is the body's ability to adapt to changing energy demand and nutrient supply. Maternal undernutrition causes growth restriction at birth and subsequent obesity development. Intriguingly, metabolic flexibility is maintained due to adaptations of muscle tissue. The aim of the present study was to investigate developmental pathways of these adaptive changes. Wistar rats received standard chow at either ad libitum (AD) or 30% of ad libitum intake (UN) throughout pregnancy. At all ages, metabolic status indicated similar insulin sensitivity in AD and UN offspring despite the development of adiposity in UN offspring at weaning. Type IIA fiber size was reduced in soleus muscle of UN offspring at weaning and they had a higher percentage of type I fibers in adulthood with a concomitantly higher oxidative capacity. Plasticity of muscle was present during the postnatal period and proposes novel pathways for the dynamic development of metabolic flexibility throughout postnatal life.

Dietary methyl donor deficiency during pregnancy in rats shapes learning and anxiety in offspring.

Two important lines of research have enhanced our understanding of the molecular role of nutrition in influencing behavior. First, exposure to an adverse environment during early life can influence the long-term behavior of the offspring. Second, regulation of the nervous system development and functioning appears to involve epigenetic mechanisms that require a continuous supply of methyl group donors in food. We hypothesized that a maternal diet during pregnancy deficient in methyl donors (MDD) may lead to altered behavior in offspring through permanent changes in hippocampal DNA methylation. We used a rat model of prenatal dietary MDD to test this hypothesis in female offspring as they aged. Prenatal MDD reduced birth weight, litter size, and newborn viability. Aged female offspring of MDD mothers showed increased anxiety and increased learning ability in comparison with control diet group offspring. To explore the role of MDD on epigenetic mechanisms in the brain of adult offspring, we studied expression and methylation of 4 selected genes coding for glucocorticoid receptor, hydroxysteroid dehydrogenase 11 type 2, neuronatin, and reelin proteins in the hippocampus. No major group differences in methylation or expression of the studied genes were detected, except for a significant down-regulation of the reelin gene in the MDD female offspring. The prenatal MDD diet caused intrauterine growth restriction, associated with long-term effects on the behavior of the offspring. However, the observed behavioral differences between the MDD and control diet offspring cannot be explained by epigenetic regulation of the specific genes investigated in this study.

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes.

BACKGROUND: Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue. METHODS: The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways. RESULTS: Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor ß protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue. CONCLUSIONS: A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.

Pre- and postnatal methyl deficiency in the rat differentially alters glucose homeostasis.

BACKGROUND/AIMS: Early-life methyl-donor deficiency is implicated in growth restriction and later-life development of type 2 diabetes mellitus. We ascertained whether dietary methyl-donor deficiency in the mother during pregnancy or during postweaning growth in the rat would impair glucose homeostasis, insulin secretion and pancreatic endocrine development in young adults. METHODS: Effects of maternal methyl deficiency (90% deficiency in methionine, folate and choline) were compared with those of postweaning methyl deficiency and with control diets for effects on growth, impaired glucose tolerance, insulin secretion and pancreas development in offspring. Studies focussed on male offspring, which have been shown more susceptible to early-life influences on later disease development. RESULTS: Prenatal methyl deficiency delayed delivery, restricted birthweight by 22%, reduced litter size by 33% and increased offspring mortality to 23% shortly after birth. It reduced relative endocrine pancreatic mass in adult male offspring to 46% of endocrine mass in controls, but only mildly impaired their glucose tolerance and insulin secretion. In contrast, postweaning methyl deficiency restricted growth of male rats and reduced relative pancreatic endocrine mass (-40%), but improved their glucose tolerance, despite decreased insulin secretion. CONCLUSION: It is clear that the global undernutrition (UN) during pregnancy in rodents alters glucose metabolism in adult offspring. It has been hypothesised that alterations in epigenetic mechanisms may underlie this phenotype. However, removing all methyl donors during pregnancy, which are essential for epigenetic processes in development, did not cause any alteration in glucose metabolism in offspring as seen in the global UN model.

Maternal supplementation with a complex milk lipid mixture during pregnancy and lactation alters neonatal brain lipid composition but lacks effect on cognitive function in rats.

Complex milk lipids (CMLs) provide a critical nutritional source for generating both energy and essential nutrients for the growth of the newborn. The present study investigated nutritional supplementation with a CML containing gangliosides and phospholipids in pregnant and lactating rats on learning behavior and postnatal growth in male offspring. Wistar female rats were supplemented during pregnancy and lactation with either control or CML to provide gangliosides at a dose of 0.01% (low) and 0.05% (high) based on total food intake. The CML-supplemented dams showed no differences in comparison to controls regarding growth, food intake, and litter characteristics. There were significant differences in brain composition in male offspring at postnatal day 2 (P2) with higher concentrations of gangliosides (high dose, P < .05) and lower concentrations of phospholipids (low and high dose, P < .05) in the CML-supplemented groups. The distribution of individual ganglioside species was not significantly different between treatment groups. Brain weight at P2 was also significantly higher in the CML groups. Differences in the brain composition and weight were not significant by weaning (P21). As adults (P80), adiposity was reduced in the low CML-supplemented group compared to controls. No significant differences were detected between any of the treatment groups in any of the behavioral tasks (water maze, object recognition, and operant learning). These data suggest that maternal supplementation with a CML during pregnancy and lactation is safe and has a significant early impact on brain weight and ganglioside and phospholipid content in offspring but did not alter long-term behavioral function using standard behavioral techniques.