Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: the METS-microbiome study.

The relationship between microbiota, short chain fatty acids (SCFAs), and obesity remains enigmatic. We employ amplicon sequencing and targeted metabolomics in a large (n = 1904) African origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US. Microbiota diversity and fecal SCFAs are greatest in Ghanaians, and lowest in Americans, representing each end of the urbanization spectrum. Obesity is significantly associated with a reduction in SCFA concentration, microbial diversity, and SCFA synthesizing bacteria, with country of origin being the strongest explanatory factor. Diabetes, glucose state, hypertension, obesity, and sex can be accurately predicted from the global microbiota, but when analyzed at the level of country, predictive accuracy is only universally maintained for sex. Diabetes, glucose, and hypertension are only predictive in certain low-income countries. Our findings suggest that adiposity-related microbiota differences differ between low-to-middle-income compared to high-income countries. Further investigation is needed to determine the factors driving this association.

Gut microbiota and fecal short chain fatty acids differ with adiposity and country of origin: The METS-Microbiome Study.

The relationship between the gut microbiota, short chain fatty acid (SCFA) metabolism, and obesity remains unclear due to conflicting reports from studies with limited statistical power. Additionally, this association has rarely been explored in large scale diverse populations. Here, we investigated associations between fecal microbial composition, predicted metabolic potential, SCFA concentrations, and obesity in a large ( N = 1,934) adult cohort of African-origin spanning the epidemiologic transition, from Ghana, South Africa, Jamaica, Seychelles, and the United States (US). The greatest gut microbiota diversity and total fecal SCFA concentration was found in the Ghanaian population, while the lowest levels were found in the US population, respectively representing the lowest and the highest end of the epidemiologic transition spectrum. Country-specific bacterial taxa and predicted-functional pathways were observed, including an increased prevalence of Prevotella , Butyrivibrio , Weisella and Romboutsia in Ghana and South Africa, while Bacteroides and Parabacteroides were enriched in Jamaican and the US populations. Importantly, 'VANISH' taxa, including Butyricicoccus and Succinivibrio , were significantly enriched in the Ghanaian cohort, reflecting the participants' traditional lifestyles. Obesity was significantly associated with lower SCFA concentrations, a decrease in microbial richness, and dissimilarities in community composition, and reduction in the proportion of SCFA synthesizing bacteria including Oscillospira , Christensenella , Eubacterium , Alistipes , Clostridium and Odoribacter . Further, the predicted proportions of genes in the lipopolysaccharide (LPS) synthesis pathway were enriched in obese individuals, while genes associated with butyrate synthesis via the dominant pyruvate pathway were significantly reduced in obese individuals. Using machine learning, we identified features predictive of metabolic state and country of origin. Country of origin could accurately be predicted by the fecal microbiota (AUC = 0.97), whereas obesity could not be predicted as accurately (AUC = 0.65). Participant sex (AUC = 0.75), diabetes status (AUC = 0.63), hypertensive status (AUC = 0.65), and glucose status (AUC = 0.66) could all be predicted with different success. Interestingly, within country, the predictive accuracy of the microbiota for obesity was inversely correlated to the epidemiological transition, being greatest in Ghana (AUC = 0.57). Collectively, our findings reveal profound variation in the gut microbiota, inferred functional pathways, and SCFA synthesis as a function of country of origin. While obesity could be predicted accurately from the microbiota, the variation in accuracy in parallel with the epidemiological transition suggests that differences in the microbiota between obesity and non-obesity may be larger in low-to-middle countries compared to high-income countries. Further examination of independent study populations using multi-omic approaches will be necessary to determine the factors that drive this association.

The effect of wasting and stunting during severe acute malnutrition in infancy on insulin sensitivity and insulin clearance in adult life.

Adults who had non-edematous severe acute malnutrition (SAM) during infancy (i.e., marasmus) have worse glucose tolerance and beta-cell function than survivors of edematous SAM (i.e., kwashiorkor). We hypothesized that wasting and/or stunting in SAM is associated with lower glucose disposal rate (M) and insulin clearance (MCR) in adulthood.We recruited 40 nondiabetic adult SAM survivors (20 marasmus survivors (MS) and 20 kwashiorkor survivors (KS)) and 13 matched community controls. We performed 150-minute hyperinsulinaemic, euglycaemic clamps to estimate M and MCR. We also measured serum adiponectin, anthropometry, and body composition. Data on wasting (weight-for-height) and stunting (height-for-age) were abstracted from the hospital records.Children with marasmus had lower weight-for-height z-scores (WHZ) (-3.8 ± 0.9 vs. -2.2 ± 1.4; P < 0.001) and lower height-for-age z-scores (HAZ) (-4.6 ± 1.1 vs. -3.4 ± 1.5; P = 0.0092) than those with kwashiorkor. As adults, mean age (SD) of participants was 27.2 (8.1) years; BMI was 23.6 (5.0) kg/m2. SAM survivors and controls had similar body composition. MS and KS and controls had similar M (9.1 ± 3.2; 8.7 ± 4.6; 6.9 ± 2.5 mg.kg-1.min-1 respectively; P = 0.3) and MCR. WHZ and HAZ were not associated with M, MCR or adiponectin even after adjusting for body composition.Wasting and stunting during infancy are not associated with insulin sensitivity and insulin clearance in lean, young, adult survivors of SAM. These data are consistent with the finding that glucose intolerance in malnutrition survivors is mostly due to beta-cell dysfunction.

Liver fat in adult survivors of severe acute malnutrition.

The association between severe acute malnutrition (SAM) in early childhood and liver fat in adults is unknown. We hypothesized that exposure to SAM, especially severe wasting, is associated with fatty liver later in life. In this observational study, abdominal CT was used to quantify mean liver attenuation (MLA) and liver:spleen attenuation ratio (L/S). Birth weight (BW), serum lipids, insulin resistance (homeostatic model assessment), anthropometry and intrabdominal fat were collected. Mean differences between diagnostic groups were tested and hierarchical regression analysis determined the best predictors of liver fat. We studied 88 adult SAM survivors and 84 community participants (CPs); age 29.0 ± 8.4 years, BMI 23.5 ± 5.0 kg/m2 (mean ± SDs). SAM survivors had less liver fat than CPs (using L/S) (p = 0.025). Severe wasting survivors (SWs) had lower BW (-0.51 kg; p = 0.02), were younger, thinner and had smaller waist circumference than oedematous malnutrition survivors (OMs). In the final regression model adjusting for age, sex, birth weight and SAM phenotype (i.e., oedematous malnutrition or severe wasting), SWs had more liver fat than OMs (using MLA) (B = 2.6 ± 1.3; p = 0.04) but similar liver fat using L/S (p = 0.07) and lower BW infants had less liver fat (MLA) (B = -1.8 ± 0.8; p = 0.03). Greater liver fat in SWs than OMs, despite having less body fat, supports our hypothesis of greater cardiometabolic risk in SWs. Other postnatal factors might influence greater liver fat in survivors of severe wasting, suggesting the need to monitor infants exposed to SAM beyond the acute episode.

Gut microbiota alterations in response to sleep length among African-origin adults.

Sleep disorders are increasingly being characterized in modern society as contributing to a host of serious medical problems, including obesity and metabolic syndrome. Changes to the microbial community in the human gut have been reportedly associated with many of these cardiometabolic outcomes. In this study, we investigated the impact of sleep length on the gut microbiota in a large cohort of 655 participants of African descent, aged 25-45, from Ghana, South Africa (SA), Jamaica, and the United States (US). The sleep duration was self-reported via a questionnaire. Participants were classified into 3 sleep groups: short (<7hrs), normal (7-<9hrs), and long (≥9hrs). Forty-seven percent of US participants were classified as short sleepers and 88% of SA participants as long sleepers. Gut microbial composition analysis (16S rRNA gene sequencing) revealed that bacterial alpha diversity negatively correlated with sleep length (p<0.05). Furthermore, sleep length significantly contributed to the inter-individual beta diversity dissimilarity in gut microbial composition (p<0.01). Participants with both short and long-sleep durations exhibited significantly higher abundances of several taxonomic features, compared to normal sleep duration participants. The predicted relative proportion of two genes involved in the butyrate synthesis via lysine pathway were enriched in short sleep duration participants. Finally, co-occurrence relationships revealed by network analysis showed unique interactions among the short, normal and long duration sleepers. These results suggest that sleep length in humans may alter gut microbiota by driving population shifts of the whole microbiota and also specific changes in Exact Sequence Variants abundance, which may have implications for chronic inflammation associated diseases. The current findings suggest a possible relationship between disrupted sleep patterns and the composition of the gut microbiota. Prospective investigations in larger and more prolonged sleep researches and causally experimental studies are needed to confirm these findings, investigate the underlying mechanism and determine whether improving microbial homeostasis may buffer against sleep-related health decline in humans.

Evolution of water conservation in humans.

To sustain life, humans and other terrestrial animals must maintain a tight balance of water gain and water loss each day.1-3 However, the evolution of human water balance physiology is poorly understood due to the absence of comparative measures from other hominoids. While humans drink daily to maintain water balance, rainforest-living great apes typically obtain adequate water from their food and can go days or weeks without drinking4-6. Here, we compare isotope-depletion measures of water turnover (L/d) in zoo- and rainforest-sanctuary-housed apes (chimpanzees, bonobos, gorillas, and orangutans) with 5 diverse human populations, including a hunter-gatherer community in a semi-arid savannah. Across the entire sample, water turnover was strongly related to total energy expenditure (TEE, kcal/d), physical activity, climate (ambient temperature and humidity), and fat free mass. In analyses controlling for those factors, water turnover was 30% to 50% lower in humans than in other apes despite humans' greater sweating capacity. Water turnover in zoo and sanctuary apes was similar to estimated turnover in wild populations, as was the ratio of water intake to dietary energy intake (∼2.8 mL/kcal). However, zoo and sanctuary apes ingested a greater ratio of water to dry matter of food, which might contribute to digestive problems in captivity. Compared to apes, humans appear to target a lower ratio of water/energy intake (∼1.5 mL/kcal). Water stress due to changes in climate, diet, and behavior apparently led to previously unknown water conservation adaptations in hominin physiology.

Childhood severe acute malnutrition is associated with metabolic changes in adulthood.

BACKGROUNDSevere acute malnutrition (SAM) is a major contributor to global mortality in children under 5 years. Mortality has decreased; however, the long-term cardiometabolic consequences of SAM and its subtypes, severe wasting (SW) and edematous malnutrition (EM), are not well understood. We evaluated the metabolic profiles of adult SAM survivors using targeted metabolomic analyses.METHODSThis cohort study of 122 adult SAM survivors (SW = 69, EM = 53) and 90 age-, sex-, and BMI-matched community participants (CPs) quantified serum metabolites using direct flow injection mass spectrometry combined with reverse-phase liquid chromatography. Univariate and sparse partial least square discriminant analyses (sPLS-DAs) assessed differences in metabolic profiles and identified the most discriminative metabolites.RESULTSSeventy-seven metabolite variables were significant in distinguishing between SAM survivors (28.4 ± 8.8 years, 24.0 ± 6.1 kg/m2) and CPs (28.4 ± 8.9 years, 23.3 ± 4.4 kg/m2) (mean ± SDs) in univariate and sPLS-DA models. Compared with CPs, SAM survivors had less liver fat; higher branched-chain amino acids (BCAAs), urea cycle metabolites, and kynurenine/tryptophan (KT) ratio (P < 0.001); and lower ß-hydroxybutyric acid and acylcarnitine/free carnitine ratio (P < 0.001), which were both associated with hepatic steatosis (P < 0.001). SW and EM survivors had similar metabolic profiles as did stunted and nonstunted SAM survivors.CONCLUSIONAdult SAM survivors have distinct metabolic profiles that suggest reduced ß-oxidation and greater risk of type 2 diabetes (BCAAs, KT ratio, urea cycle metabolites) compared with CPs. This indicates that early childhood SAM exposure has long-term metabolic consequences that may worsen with age and require targeted clinical management.FUNDINGHealth Research Council of New Zealand, Caribbean Public Health Agency, Centre for Global Child Health at the Hospital for Sick Children. DST is an Academic Fellow and a Restracomp Fellow at the Centre for Global Child Health. GBG is a postdoctoral fellow of the Research Foundation Flanders.

Nonalcoholic Fatty Liver Disease in Nonobese Subjects of African Origin Has Atypical Metabolic Characteristics.

BACKGROUND: Nonobese nonalcoholic fatty liver disease is reported in several populations. However, because persons of African origin display unique fat accumulation, insulin resistance, and lipid profiles, we investigated fatty liver in nonobese persons of African origin. METHOD: We recruited 78 urban Jamaican volunteers. CT was used to estimate liver and abdominal fat and dual-energy X-ray absorptiometry to measure body composition. Fasting blood was collected for lipids, alanine aminotransferase (ALT), adiponectin, and fetuin-A. Homeostatic model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), insulinogenic index (IGI), and oral disposition index (oDI) were calculated after a 75-g oral glucose tolerance test. RESULTS: Fifty-two percent of participants were male; mean (±SD) age was 28.5 ± 7.8 years, and body mass index was 22.4 ± 3.0 kg/m2. Mean liver attenuation (MLA) and liver/spleen (LS) ratio, both inversely correlated to liver fat, were 62.8 ± 4.3 HU and 1.2 ± 0.1, respectively; 3.8% of participants had liver fat >30% (LS ratio < 1). In age, sex, and BMI-adjusted correlations, MLA was negatively associated with weight (r = -0.30; P = 0.009) and height (r = -0.28; P = 0.017) and was associated with fasting glucose (r = 0.23; P = 0.05), fasting insulin (r = 0.42; P ≤ 0.001) and HOMA-IR (r = 0.35; P = 0.004). Serum lipids, ALT, adiponectin, fetuin-A, WBISI, IGI, and oDI were not associated with liver fat. CONCLUSIONS: In nonobese Afro-Caribbean participants, greater liver fat was associated with weight and height and lower fasting insulin and hyperinsulinemia appears to be influential in the reduction of NAFLD. These findings may be influenced by ethnicity, body size, and method of estimating liver fat.

The human microbiota is associated with cardiometabolic risk across the epidemiologic transition.

Oral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, and Prevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associated Streptococcus, Prevotella, and Veillonella were enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.

Gut microbiota, short chain fatty acids, and obesity across the epidemiologic transition: the METS-Microbiome study protocol.

BACKGROUND: While some of the variance observed in adiposity and weight change within populations can be accounted for by traditional risk factors, a new factor, the gut microbiota, has recently been associated with obesity. However, the causal mechanisms through which the gut microbiota and its metabolites, short chain fatty acids (SCFAs) influence obesity are unknown, as are the individual obesogenic effects of the individual SCFAs (butyrate, acetate and propionate). This study, METS-Microbiome, proposes to examine the influence of novel risk factors, the gut microbiota and SCFAs, on obesity, adiposity and weight change in an international established cohort spanning the epidemiologic transition. METHODS: The parent study; Modeling the Epidemiologic Transition Study (METS) is a well-established and ongoing prospective cohort study designed to assess the association between body composition, physical activity, and relative weight, weight gain and cardiometabolic disease risk in five diverse population-based samples in 2500 people of African descent. The cohort has been prospectively followed since 2009. Annual measures of obesity risk factors, including body composition, objectively measured physical activity and dietary intake, components which vary across the spectrum of social and economic development. In our new study; METS-Microbiome, in addition to continuing yearly measures of obesity risk, we will also measure gut microbiota and stool SCFAs in all contactable participants, and follow participants for a further 3 years, thus providing one of the largest gut microbiota population-based studies to date. DISCUSSION: This new study capitalizes upon an existing, extensively well described cohort of adults of African-origin, with significant variability as a result of the widespread geographic distributions, and therefore variation in the environmental covariate exposures. The METS-Microbiome study will substantially advance the understanding of the role gut microbiota and SCFAs play in the development of obesity and provide novel obesity therapeutic targets targeting SCFAs producing features of the gut microbiota. TRIAL REGISTRATION: Registered NCT03378765 Date first posted: December 20, 2017.

The Association of Dietary Fiber Intake with Cardiometabolic Risk in Four Countries across the Epidemiologic Transition.

The greatest burden of cardiovascular disease is now carried by developing countries with cardiometabolic conditions such as metabolic syndrome, obesity and inflammation believed to be the driving force behind this epidemic. Dietary fiber is known to have protective effects against obesity, type 2 diabetes, cardiovascular disease and the metabolic syndrome. Considering the emerging prevalence of these cardiometabolic disease states across the epidemiologic transition, the objective of this study is to explore these associations of dietary fiber with cardiometabolic risk factors in four countries across the epidemiologic transition. We examined population-based samples of men and women, aged 25⁻45 of African origin from Ghana, Jamaica, the Seychelles and the USA. Ghanaians had the lowest prevalence of obesity (10%), while Jamaicans had the lowest prevalence of metabolic syndrome (5%) across all the sites. Participants from the US presented with the highest prevalence of obesity (52%), and metabolic syndrome (22%). Overall, the Ghanaians consumed the highest dietary fiber (24.9 ± 9.7 g), followed by Jamaica (16.0 ± 8.3 g), the Seychelles (13.6 ± 7.2 g) and the lowest in the USA (14.2 ± 7.1 g). Consequently, 43% of Ghanaians met the fiber dietary guidelines (14 g/1000 kcal/day), 9% of Jamaicans, 6% of Seychellois, and only 3% of US adults. Across all sites, cardiometabolic risk (metabolic syndrome, inflammation and obesity) was inversely associated with dietary fiber intake, such that the prevalence of metabolic syndrome was 13% for those in the lowest quartile of fiber intake, compared to 9% those in the highest quartile of fiber intake. Notably, twice as many of participants (38%) in the lowest quartile were obese compared to those in the highest quartile of fiber intake (18%). These findings further support the need to incorporate strategies and policies to promote increased dietary fiber intake as one component for the prevention of cardiometabolic risk in all countries spanning the epidemiologic transition.

Independent association of resting energy expenditure with blood pressure: confirmation in populations of the African diaspora.

BACKGROUND: Obesity is a major risk factor for hypertension, however, the physiologic mechanisms linking increased adiposity to elevations in blood pressure are not well described. An increase in resting energy expenditure (REE) is an obligatory consequence of obesity. Previous survey research has demonstrated that REE is an independent predictor of blood pressure, and eliminates the co-linear association of body mass index. This observation has received little attention and there have been no attempts to provide a causal explanation. METHODS: At baseline in an international comparative study on obesity, 289 participants aged 25-44 were recruited from communities in the US, the Seychelles, Ghana and South Africa and had REE measured with indirect calorimetry. All participants were thought to be free of major illness. RESULTS: In multivariate regression models, both systolic and diastolic blood pressure were positively associated with REE (p < 0.01), while body mass index and fat mass were negatively correlated with systolic blood pressure (p < 0.01, and p < 0.05 respectively), but not diastolic blood pressure. CONCLUSIONS: These data confirm previous reports and suggest that a common physiologic abnormality links REE and blood pressure. Elevated catecholamines, a putative metabolic characteristic of obesity, is a possible candidate to explain this association. The direct role of excess adipose tissue is open to question.

Cardiovascular risk status of Afro-origin populations across the spectrum of economic development: findings from the Modeling the Epidemiologic Transition Study.

BACKGROUND: Cardiovascular risk factors are increasing in most developing countries. To date, however, very little standardized data has been collected on the primary risk factors across the spectrum of economic development. Data are particularly sparse from Africa. METHODS: In the Modeling the Epidemiologic Transition Study (METS) we examined population-based samples of men and women, ages 25-45 of African ancestry in metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. Key measures of cardiovascular disease risk are described. RESULTS: The risk factor profile varied widely in both total summary estimates of cardiovascular risk and in the magnitude of component factors. Hypertension ranged from 7% in women from Ghana to 35% in US men. Total cholesterol was well under 200 mg/dl for all groups, with a mean of 155 mg/dl among men in Ghana, South Africa and Jamaica. Among women total cholesterol values varied relatively little by country, following between 160 and 178 mg/dl for all 5 groups. Levels of HDL-C were virtually identical in men and women from all study sites. Obesity ranged from 64% among women in the US to 2% among Ghanaian men, with a roughly corresponding trend in diabetes. Based on the Framingham risk score a clear trend toward higher total risk in association with socioeconomic development was observed among men, while among women there was considerable overlap, with the US participants having only a modestly higher risk score. CONCLUSIONS: These data provide a comprehensive estimate of cardiovascular risk across a range of countries at differing stages of social and economic development and demonstrate the heterogeneity in the character and degree of emerging cardiovascular risk. Severe hypercholesterolemia, as characteristic in the US and much of Western Europe at the onset of the coronary epidemic, is unlikely to be a feature of the cardiovascular risk profile in these countries in the foreseeable future, suggesting that stroke may remain the dominant cardiovascular event.

Socioeconomic factors associated with severe acute malnutrition in Jamaica.

OBJECTIVES: Severe acute malnutrition (SAM) is an important risk factor for illness and death globally, contributing to more than half of deaths in children worldwide. We hypothesized that SAM is positively correlated to poverty, low educational attainment, major crime and higher mean soil concentrations of lead, cadmium and arsenic. METHODS: We reviewed admission records of infants admitted with a diagnosis of SAM over 14 years (2000-2013) in Jamaica. Poverty index, educational attainment, major crime and environmental heavy metal exposure were represented in a Geographic Information System (GIS). Cases of SAM were grouped by community and the number of cases per community/year correlated to socioeconomic variables and geochemistry data for the relevant year. RESULTS: 375 cases of SAM were mapped across 204 urban and rural communities in Jamaica. The mean age at admission was 9 months (range 1-45 months) and 57% were male. SAM had a positive correlation with major crime (r = 0.53; P < 0.001), but not with educational attainment or the poverty index. For every one unit increase in the number of crimes reported, the rate of occurrence of SAM cases increased by 1.01% [Incidence rate ratio (IRR) = 1.01 (95% CI = 1.006-1.014); P P<0.001]. The geochemistry data yielded no correlation between levels of heavy metals and the prevalence of malnutrition. CONCLUSION: Major crime has an independent positive association with severe acute malnutrition in Jamaican infants. This could suggest that SAM and major crime might have similar sociological origins or that criminality at the community level may be indicative of reduced income opportunities with the attendant increase in poor nutrition in the home.

Accelerometer-measured physical activity is not associated with two-year weight change in African-origin adults from five diverse populations.

BACKGROUND: Increasing population-levels of physical activity (PA) is a controversial strategy for managing the obesity epidemic, given the conflicting evidence for weight loss from PA alone per se. We measured PA and weight change in a three-year prospective cohort study in young adults from five countries (Ghana, South Africa, Jamaica, Seychelles and USA). METHODS: A total of 1,944 men and women had baseline data, and at least 1 follow-up examination including measures of anthropometry (weight/BMI), and objective PA (accelerometer, 7-day) following the three-year study period. PA was explored as 1-minute bouts of moderate and vigorous PA (MVPA) as well as daily sedentary time. RESULTS: At baseline; Ghanaian and South African men had the lowest body weights (63.4 ± 9.5, 64.9 ± 11.8 kg, respectively) and men and women from the USA the highest (93.6 ± 25.9, 91.7 ± 23.4 kg, respectively). Prevalence of normal weight ranged from 85% in Ghanaian men to 29% in USA men and 52% in Ghanaian women to 15% in USA women. Over the two-year follow-up period, USA men and Jamaican women experienced the smallest yearly weight change rate (0.1 ± 3.3 kg/yr; -0.03 ± 3.0 kg/yr, respectively), compared to South African men and Ghanaian women greatest yearly change (0.6.0 ± 3.0 kg/yr; 1.22 ± 2.6 kg/yr, respectively). Mean yearly weight gain tended to be larger among normal weight participants at baseline than overweight/obese at baseline. Neither baseline MVPA nor sedentary time were associated with weight gain. Using multiple linear regression, only baseline weight, age and gender were significantly associated with weight gain. DISCUSSION: From our study it is not evident that higher volumes of PA alone are protective against future weight gain, and by deduction our data suggest that other environmental factors such as the food environment may have a more critical role.

The social patterning of risk factors for noncommunicable diseases in five countries: evidence from the modeling the epidemiologic transition study (METS).

BACKGROUND: Associations between socioeconomic status (SES) and risk factors for noncommunicable diseases (NCD-RFs) may differ in populations at different stages of the epidemiological transition. We assessed the social patterning of NCD-RFs in a study including populations with different levels of socioeconomic development. METHODS: Data on SES, smoking, physical activity, body mass index, blood pressure, cholesterol and glucose were available from the Modeling the Epidemiologic Transition Study (METS), with about 500 participants aged 25-45 in each of five sites (Ghana, South Africa, Jamaica, Seychelles, United States). RESULTS: The prevalence of NCD-RFs differed between these populations from five countries (e.g., lower prevalence of smoking, obesity and hypertension in rural Ghana) and by sex (e.g., higher prevalence of smoking and physical activity in men and of obesity in women in most populations). Smoking and physical activity were associated with low SES in most populations. The associations of SES with obesity, hypertension, cholesterol and elevated blood glucose differed by population, sex, and SES indicator. For example, the prevalence of elevated blood glucose tended to be associated with low education, but not with wealth, in Seychelles and USA. The association of SES with obesity and cholesterol was direct in some populations but inverse in others. CONCLUSIONS: In conclusion, the distribution of NCD-RFs was socially patterned in these populations at different stages of the epidemiological transition, but associations between SES and NCD-RFs differed substantially according to risk factor, population, sex, and SES indicator. These findings emphasize the need to assess and integrate the social patterning of NCD-RFs in NCD prevention and control programs in LMICs.

Metabolic acceleration and the evolution of human brain size and life history.

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

Developmental contributions to macronutrient selection: a randomized controlled trial in adult survivors of malnutrition.

BACKGROUND AND OBJECTIVES: Birthweight differences between kwashiorkor and marasmus suggest that intrauterine factors influence the development of these syndromes of malnutrition and may modulate risk of obesity through dietary intake. We tested the hypotheses that the target protein intake in adulthood is associated with birthweight, and that protein leveraging to maintain this target protein intake would influence energy intake (EI) and body weight in adult survivors of malnutrition. METHODOLOGY: Sixty-three adult survivors of marasmus and kwashiorkor could freely compose a diet from foods containing 10, 15 and 25 percentage energy from protein (percentage of energy derived from protein (PEP); Phase 1) for 3 days. Participants were then randomized in Phase 2 (5 days) to diets with PEP fixed at 10%, 15% or 25%. RESULTS: Self-selected PEP was similar in both groups. In the groups combined, selected PEP was 14.7, which differed significantly (P < 0.0001) from the null expectation (16.7%) of no selection. Self-selected PEP was inversely related to birthweight, the effect disappearing after adjusting for sex and current body weight. In Phase 2, PEP correlated inversely with EI (P = 0.002) and weight change from Phase 1 to 2 (P = 0.002). Protein intake increased with increasing PEP, but to a lesser extent than energy increased with decreasing PEP. CONCLUSIONS AND IMPLICATIONS: Macronutrient intakes were not independently related to birthweight or diagnosis. In a free-choice situation (Phase 1), subjects selected a dietary PEP significantly lower than random. Lower PEP diets induce increased energy and decreased protein intake, and are associated with weight gain.

Evidence for daily and weekly rhythmicity but not lunar or seasonal rhythmicity of physical activity in a large cohort of individuals from five different countries.

BACKGROUND: Biological rhythmicity has been extensively studied in animals for many decades. Although temporal patterns of physical activity have been identified in humans, no large-scale, multi-national study has been published, and no comparison has been attempted of the ubiquity of activity rhythms at different time scales (such as daily, weekly, monthly, and annual). METHODS: Using individually worn actigraphy devices, physical activity of 2,328 individuals from five different countries (adults of African descent from Ghana, South Africa, Jamaica, Seychelles, and the United States) was measured for seven consecutive days at different times of the year. RESULTS: Analysis for rhythmic patterns identified daily rhythmicity of physical activity in all five of the represented nationalities. Weekly rhythmicity was found in some, but not all, of the nationalities. No significant evidence of lunar rhythmicity or seasonal rhythmicity was found in any of the groups. CONCLUSIONS: These findings extend previous small-scale observations of daily rhythmicity to a large cohort of individuals from around the world. The findings also confirm the existence of modest weekly rhythmicity but not lunar or seasonal rhythmicity in human activity. These differences in rhythm strength have implications for the management of health hazards of rhythm misalignment.