Programming effects of glucose, fructose or galactose in post-weaning diet on adiposity and serum adipokines in adult mice
Bouwman, L.M.S. ; Fernández Calleja, J.M.S. ; Keijer, J. ; Oosting, A. ; Schothorst, E.M. van - \ 2016
programming effects - glucose - fructose - post-weaning diet - adiposity - serum adipokines
Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity
Vrieze, A. ; Out, C. ; Fuentes Enriquez de Salamanca, S. ; Jonker, L. ; Reuling, I. ; Kootte, R.S. ; Nood, E. van; Holleman, F. ; Knaapen, M. ; Romijn, J.A. ; Soeters, M.R. ; Blaak, E.E. ; Dallinga-Thie, G.M. ; Reijnders, D. ; Ackermans, M.T. ; Serlie, M.J. ; Knop, F.K. ; Holst, J.J. ; Ley, C.V. ; Kema, I.P. ; Zoetendal, E.G. ; Vos, W.M. de; Hoekstra, J.B. ; Stroes, E.S. ; Groen, A.K. ; Nieuwdorp, M. - \ 2014
Journal of Hepatology 60 (2014)4. - ISSN 0168-8278 - p. 824 - 831.
salt hydrolase activity - diet-induced obesity - intestinal microbiota - energy-expenditure - mice - resistance - adiposity - glucagon - capacity - humans
BACKGROUND: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism. METHODS: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500mg t.i.d. or 7 days of vancomycin 500mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p
Effects of diet history on energy metabolism and physiological parameters in C57BL/6J mice
Hoevenaars, F.P.M. ; Keijer, J. ; Swarts, J.J.M. ; Snaas-Alders, S.H. ; Bekkenkamp-Grovenstein, M. ; Schothorst, E.M. van - \ 2013
Experimental Physiology 98 (2013)5. - ISSN 0958-0670 - p. 1053 - 1062.
body-weight - skeletal-muscle - settling points - induced obesity - fat-metabolism - set points - follow-up - expenditure - maintenance - adiposity
Understanding body weight regulation is essential to fight obesity. Mouse studies, using different types of diets, showed conflicting results in terms of body weight persistence after changing from an ad libitum high-fat diet to an ad libitum low-fat diet. In this study, we questioned specifically whether the energy content of the diet has a lasting effect on energy balance and body weight, using multiple switches and two purified diets with a different fat-to-sugar ratio, but otherwise identical ingredients. Young-adult obesity-prone male C57BL/6J mice were fed single or double switches of semi-purified diets with either 10 energy % (en%) fat (LF) or 40en% fat (HF), with starch replaced by fat, while protein content remained equal. After none, one or two dietary changes, energy metabolism was assessed at 5, 14 and 19 weeks. We observed no systematic continuous compensation in diet and energy intake when returning to LF after HF consumption. Body weight, white adipose tissue mass and histology, serum metabolic parameters, energy expenditure and substrate usage all significantly reflected the current diet intake, independent of dietary changes. This contrasts with studies that used diets with different ingredients and showed persistent effects of dietary history on body weight, suggesting diet-dependent metabolic set points. We conclude that body weight and metabolic parameters 'settle', based on current energetic input and output. This study also highlights the importance of considering the choice of diet in physiological and metabolic intervention studies.
Richness of human gut microbiome correlates with metabolic markers
Chatelier, E. Le; Nielsen, T. ; Qin, J. ; Prifti, E. ; Hildebrand, F. ; Falony, G. ; Almeida, M. ; Arumugam, M. ; Batto, J.M. ; Kennedy, S. ; Leonard, P. ; Li, J. ; Burgdorf, K. ; Grarup, N. ; Jorgensen, T. ; Branslund, I. ; Nielsen, H.B. ; Juncker, A.S. ; Bertalan, M. ; Levenez, F. ; Pons, N. ; Rasmussen, S. ; Sunagawa, S. ; Tap, J. ; Tims, S. ; Zoetendal, E.G. ; Brunak, S. ; Clement, K. ; Dore, J. ; Kleerebezem, M. ; Kristiansen, K. ; Renault, P. ; Sicheritz-Ponten, T. ; Vos, W.M. de; Zucker, J.D. ; Raes, J. ; Hansen, T. ; Bork, P. ; Wang, J. ; Ehrlich, S.D. ; Pederson, O. ; Guedon, E. ; Delorme, C. ; Layec, S. ; Khaci, G. ; Guchte, M. van de; Vandemeulebrouck, G. ; Jamet, A. ; Dervyn, R. ; Sanchez, N. ; Maguin, E. ; Haimet, F. ; Winogradski, Y. ; Cultrone, A. ; Leclerc, M. ; Juste, C. ; Blottière, H. ; Pelletier, E. ; LePaslier, D. ; Artiguenave, F. ; Bruls, T. ; Weissenbach, J. ; Turner, K. ; Parkhill, J. ; Antolin, M. ; Manichanh, C. ; Casellas, F. ; Boruel, N. ; Varela, E. ; Torrejon, A. ; Guarner, F. ; Denariaz, G. ; Derrien, M. ; Hylckama Vlieg, J.E.T. van; Veiga, P. ; Oozeer, R. ; Knol, J. ; Rescigno, M. ; Brechot, C. ; M'Rini, C. ; Mérieux, A. ; Yamada, T. - \ 2013
Nature 500 (2013)7464. - ISSN 0028-0836 - p. 541 - 546.
body-mass index - diet-induced obesity - insulin-resistance - wide association - reared apart - weight-loss - inflammation - adiposity - disease - twins
We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness. They contain known and previously unknown bacterial species at different proportions; individuals with a low bacterial richness (23% of the population) are characterized by more marked overall adiposity, insulin resistance and dyslipidaemia and a more pronounced inflammatory phenotype when compared with high bacterial richness individuals. The obese individuals among the lower bacterial richness group also gain more weight over time. Only a few bacterial species are sufficient to distinguish between individuals with high and low bacterial richness, and even between lean and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities.
Phenotyping the effect of diet on non-alcoholic fatty liver disease
Wit, N.J.W. de; Afman, L.A. ; Mensink, M.R. ; Muller, M.R. - \ 2012
Journal of Hepatology 57 (2012)6. - ISSN 0168-8278 - p. 1370 - 1373.
biomarker discovery - hepatic steatosis - steatohepatitis - progression - intervention - consumption - metabolism - expression - adiposity - mice
Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and progression of NAFLD. In general, saturated fat and fructose seem to stimulate hepatic lipid accumulation and progression into NASH, whereas unsaturated fat, choline, antioxidants, and high-protein diets rich in isoflavones seem to have a more preventive effect. Knowledge of the underlying mechanisms by which diet affects NAFLD is expanding, not in the least due to innovative techniques, such as genomics tools that provide detailed comprehensive information on a large high-throughput scale. Although most nutrients seem to interfere with the balance between hepatic de novo lipogenesis (endogenous synthesis of fatty acids) and lipid oxidation (burning fat for energy), there are also indications that diet can trigger or prevent hepatic lipid accumulation by influencing the interaction between liver, gut, and adipose tissue. This review now gives a current detailed overview of diet-mediated mechanisms underlying NAFLD development and progression and summarizes recent results of genomics (transcriptomics, proteomics and metabolomics) studies that contribute to improved staging, monitoring and understanding of NAFLD pathophysiology
Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine
Wit, N.J.W. de; Derrien, M. ; Bosch-Vermeulen, H. ; Oosterink, E. ; Keshtkar, S. ; Duval, C.N.C. ; Vogel-van den Bosch, H.M. de; Kleerebezem, M. ; Muller, M.R. ; Meer, R. van der - \ 2012
American Journal of Physiology. Gastrointestinal and Liver Physiology 303 (2012)5. - ISSN 0193-1857 - p. G589 - G599.
insulin-resistance - metabolic syndrome - lipid-metabolism - c57bl/6j mice - acids - hormones - adiposity - capacity - receptor - gpr41
We studied the effect of dietary fat type, varying in polyunsaturated-to-saturated fatty acid ratios (P/S), on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1), or safflower oil (HF-SO; P/S 7.8) for 8 wk. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared with the HF-OO, HF-SO, or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes-to-Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.
Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct Study
Ekelund, U. ; Feskens, E.J.M. - \ 2012
Diabetologia 55 (2012)7. - ISSN 0012-186X - p. 1944 - 1952.
10 european countries - body-mass index - life-style - insulin sensitivity - fat distribution - heart-rate - mellitus - adiposity - accelerometry - improves
Aims/hypothesis We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. Methods The InterAct case–cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. Results A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. Conclusions/interpretation Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women.
The impact of body mass index in old age on cause-specific mortality
Hollander, E.L. de; Zutphen, M. van; Bogers, R.P. ; Bemelmans, W.J.E. ; Groot, C.P.G.M. de - \ 2012
Journal of Nutrition, Health and Aging 16 (2012)1. - ISSN 1279-7707 - p. 100 - 106.
obesity - overweight - men - consequences - underweight - guidelines - adiposity - whitehall - weight - height
Objectives: To assess the association between Body Mass Index (BMI) and cause-specific mortality in older adults and to assess which BMI was associated with lowest mortality. Design: Prospective study. Setting: European towns. Participants: 1,980 older adults, aged 70-75 years from the SENECA (Survey in Europe on Nutrition and the Elderly: a concerted action) study. Measurements: BMI, examined in 1988/1989, and mortality rates and causes of death during 10 years of follow-up. Results: Cox proportional hazards model including both BMI and BMI2, accounting for sex, smoking status, educational level and age at baseline showed that BMI was associated with all-cause mortality (p0.3). The lowest all-cause mortality risk was found at 27.1 (95%CI 24.1, 29.3) kg/m2, and this risk was increased with statistical significance when higher than 31.4 kg/m2 and lower than 21.1 kg/m2. The lowest cardiovascular mortality risk was found at 25.6 (95%CI 17.1, 28.4) kg/m2, and was increased with statistical significance when higher than 30.9 kg/m2. Conclusion: In this study, BMI was associated with all-cause mortality risk in older people. This risk was mostly driven by an increased cardiovascular mortality risk, as no association was found for mortality risk from cancer or respiratory disease. Our results indicate that the WHO cut-off point of 25 kg/m2 for overweight might be too low in old age, but more studies are needed to define specific cut-off points.
Supplementary dietary calcium stimulates faecal fat and bile acid excretion, but does not protect against obesity and insulin resistance in C57BL/6J mice
Wit, N.J.W. de; Bosch-Vermeulen, H. ; Oosterink, E. ; Müller, M.R. ; Meer, R. van der - \ 2011
The British journal of nutrition 105 (2011)7. - ISSN 0007-1145 - p. 1005 - 1011.
metabolism-related proteins - body-weight - lipid-metabolism - energy-expenditure - rna expression - dairy - milk - gain - rats - adiposity
There is increased interest in the potential protective role of dietary Ca in the development of metabolic disorders related to the metabolic syndrome. Ca-induced intestinal precipitation of fatty acids and bile acids as well as systemic metabolic effects of Ca on adipose tissue is proposed to play a causal role. In this experiment, we have studied all these aspects to validate the suggested protective effect of Ca supplementation, independent of other dietary changes, on the development of diet-induced obesity and insulin resistance. In our diet intervention study, C57BL/6J mice were fed high-fat diets differing in Ca concentrations (50 v. 150 mmol/kg). Faecal excretion analyses showed an elevated precipitation of intestinal fatty acids (2.3-fold; P
Baseline leptin and leptin reduction predict improvements in metabolic variables and long-term fat loss in obese children and adolescents: a prospective study of an inpatient weight-loss program
Murer, S.B. ; Knopfli, B.H. ; Aeberli, I. ; Jung, A. ; Wildhaber, J. ; Wildhaber-Brooks, J. ; Zimmermann, M.B. - \ 2011
American Journal of Clinical Nutrition 93 (2011)4. - ISSN 0002-9165 - p. 695 - 702.
blood-brain-barrier - serum leptin - body-weight - insulin-resistance - loss maintenance - plasma leptin - overweight - adiposity - life - intervention
Background: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain. Objective: The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss. Design: In obese children and adolescents [n = 203; mean age: 14.1 y, >98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo. Results: During the 2-mo program, mean (±SD) weight and fat loss were 13.9 ± 4.0 kg and 9.2 ± 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P <0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P <0.02). Conclusions: Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short- and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.
“Infectobesity: viral infections (especially with human adenovirus-36: Ad-36) may be a cause of obesity
Ginneken, V.J.T. van; Sitnyakowsky, L. ; Jeffery, J.E. - \ 2009
Medical Hypotheses 72 (2009)4. - ISSN 0306-9877 - p. 383 - 388.
canine-distemper virus - metabolic syndrome - national-health - us adults - prevalence - overweight - adiposity - disease - model - preadipocytes
In recent years viral infections have been recognized as possible cause of obesity, alongside the traditionally recognized causes (genetic inheritance, and behaviour/environmental causes such as diet exercise, cultural practices and stress). Although four viruses have been reported to induce obesity (infectoobesity) in animal models (chickens, mice, sheep, goat, dogs, rats and hamsters), until recently the viral etiology of human obesity has not received sufficient attention, possibly because the four viruses are not able to infect humans. In a series of papers over the last ten years, however, the group of Prof. Dhurandhar (Pennington Biomedical Research Center, LA, USA) demonstrated that a human adenovirus, adenovirus-36 (Ad-36), is capable of inducing adiposity in experimentally infected chickens, mice and non-human primates (marmosets). Ad-36 is known to increase the replication, differentiation, lipid accumulation and insulin sensitivity in fat cells and reduces those cells’ leptin secretion and expression. It also affects human primary preadipocytes. In rats increased adiposity was observed due to Ad-36 infection. Recent studies have shown that, in the USA, antibodies to Ad-36 were more prevalent in obese subjects (30%) than in non-obese subjects (11%). We postulate that Ad-36 may be a contributing factor to the worldwide rising problem of obesity. We suggest the extension of comparative virological studies between North America and Europe, and studies between discordant twins (both dizygous and monozygous)
Body mass index and waist circumference predict both 10-year nonfatal and fatal cardiovascular disease risk: study conducted in 20000 Dutch men and women aged 2-65 years
Dis, I. van; Kromhout, D. ; Geleijnse, J.M. ; Boer, J.M.A. ; Verschuren, W.M.M. - \ 2009
European Journal of Cardiovascular Prevention and Rehabilitation 16 (2009)6. - ISSN 1741-8267 - p. 729 - 734.
coronary-heart-disease - to-hip ratio - abdominal obesity - cholesterol determination - physical-activity - all-cause - mortality - adiposity - bmi - metaanalysis
Aims: Body mass index (BMI) and waist circumference (WC) are both predictors of cardiovascular diseases (CVD). We compared absolute risk, hazard ratio (HR), and population attributable risk of nonfatal and fatal CVD for BMI and WC in a large prospective cohort study with an average follow-up of 10 years. Methods and results: Anthropometric data were measured between 1993 and 1997 in a general population sample of over 20 000 men and women aged 20-65 years in the Netherlands. All risks were adjusted for age and sex. Absolute risk of nonfatal CVD was on average 10 times higher than that of fatal CVD. In obese respondents (BMI >=30 kg/m2), relative risk of fatal CVD was four-fold higher [HR=4.0 95% confidence interval (CI)=2.4-6.6], whereas risk of nonfatal CVD was two-fold higher (HR=1.8 95% CI=1.6-2.2) than in normal-weight respondents. Similar associations were observed for WC (>=88 vs. =102 vs. 94 cm in men). In persons with overweight or obesity (BMI >=25 kg/m2), half of all fatal CVD (attributable risk=54%, 95% CI=30-70) and a quarter of nonfatal CVD was ascribed to their overweight. On the population level, one-third of all fatal CVD cases could be attributed to overweight and obesity (population attributable risk=35%, 95% CI=14-52), and about one in seven of nonfatal CVD cases. Conclusion: The associations of BMI and WC with CVD risk were equally strong. Overweight and obesity had a stronger impact on fatal CVD than on nonfatal CVD