Effects of Casein, Chicken, and Pork Proteins on the Regulation of Body Fat and Blood Inflammatory Factors and Metabolite Patterns Are Largely Dependent on the Protein Level and Less Attributable to the Protein Source
Song, Shangxin ; Xia, Tianlan ; Zhu, Changqing ; Xue, Jingqi ; Fu, Qingquan ; Hua, Chun ; Hooiveld, Guido J.E.J. ; Müller, Michael ; Li, Chunbao - \ 2020
Journal of Agricultural and Food Chemistry 68 (2020)35. - ISSN 0021-8561 - p. 9398 - 9407.
high-fat diet - meat protein - obesity - rats - untargeted metabolomics
The impact of meat protein on metabolic regulation is still disputed and may be influenced by protein level. This study aimed to explore the effects of casein, pork, and chicken proteins at different protein levels (40% E vs 20% E) on body weight regulation, body fat accumulation, serum hormone levels, and inflammatory factors/metabolites in rats maintained on high-fat (45% E fat) diets for 84 d. Increased protein levels resulted in a significant reduction in body fat mass and an increase in the serum levels of the anti-inflammatory cytokine IL-10, independent of protein source. Analysis of blood via untargeted metabolomics analysis identified eight, four, and four metabolites significantly altered by protein level, protein source, and a protein level-source interaction, respectively. Together, the effects of casein, chicken, and pork protein on the regulation of body fat accumulation and blood metabolite profile are largely dependent on protein level and less attributable to the protein source.
Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr−/−.Leiden mice
Tengeler, Anouk C. ; Gart, Eveline ; Wiesmann, Maximilian ; Arnoldussen, Ilse A.C. ; Duyvenvoorde, Wim van; Hoogstad, Marloes ; Dederen, Pieter J. ; Verweij, Vivienne ; Geenen, Bram ; Kozicz, Tamas ; Kleemann, Robert ; Morrison, Martine C. ; Kiliaan, Amanda J. - \ 2020
FASEB Journal 34 (2020)7. - ISSN 0892-6638 - p. 9575 - 9593.
cerebral vasoreactivity - cognition - liver fibrosis - neuroimaging - obesity
The obesity epidemic increases the interest to elucidate impact of short-chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr−/−.Leiden mice. Ldlr−/−.Leiden mice received 16 weeks either a high-fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD-fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD-control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD-induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1-positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD-induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD-induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.
Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice
Depommier, Clara ; Hul, Matthias Van; Everard, Amandine ; Delzenne, Nathalie M. ; Vos, Willem M. de; Cani, Patrice D. - \ 2020
Gut Microbes 11 (2020)5. - ISSN 1949-0976 - p. 1231 - 1245.
Akkermansia muciniphila - brown adipose tissue metabolism - carbohydrates absorption - indirect calorimetry - intestinal turnover - mice - motor activity - obesity - pasteurization - perilipins - white adipose tissue metabolism
Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.
Ultra-Processing or Oral Processing? A Role for Energy Density and Eating Rate in Moderating Energy Intake from Processed Foods
Forde, Ciarán G. ; Mars, Monica ; Graaf, Kees De - \ 2020
Current Developments in Nutrition 4 (2020)3. - ISSN 2475-2991
eating rate - energy density - energy intake rate - food texture - metabolic disease - obesity - ultra-processed foods - unprocessed foods
Background: Recent observational data and a controlled in-patient crossover feeding trial show that consumption of "ultra-processed foods" (UPFs), as defined by the NOVA classification system, is associated with higher energy intake, adiposity, and at a population level, higher prevalence of obesity. A drawback of the NOVA classification is the lack of evidence supporting a causal mechanism for why UPFs lead to overconsumption of energy. In a recent study by Hall the energy intake rate in the UPF condition (48 kcal/min) was >50% higher than in the unprocessed condition (31 kcal/min). Extensive empirical evidence has shown the impact that higher energy density has on increasing ad libitum energy intake and body weight. A significant body of research has shown that consuming foods at higher eating rates is related to higher energy intake and a higher prevalence of obesity. Energy density can be combined with eating rate to create a measure of energy intake rate (kcal/min), providing an index of a food's potential to promote increased energy intake. Objective: The current paper compared the association between measured energy intake rate and level of processing as defined by the NOVA classification. Methods: Data were pooled from 5 published studies that measured energy intake rates across a total sample of 327 foods. Results: We show that going from unprocessed, to processed, to UPFs that the average energy intake rate increases from 35.5 ± 4.4, to 53.7 ± 4.3, to 69.4 ± 3.1 kcal/min (P < 0.05). However, within each processing category there is wide variability in the energy intake rate. Conclusions: We conclude that reported relations between UPF consumption and obesity should account for differences in energy intake rates when comparing unprocessed and ultra-processed diets. Future research requires well-controlled human feeding trials to establish the causal mechanisms for why certain UPFs can promote higher energy intake.
Trained Immunity: Linking Obesity and Cardiovascular Disease across the Life-Course?
Bekkering, Siroon ; Saner, Christoph ; Riksen, Niels P. ; Netea, Mihai G. ; Sabin, Matthew A. ; Saffery, Richard ; Stienstra, Rinke ; Burgner, David P. - \ 2020
Trends in Endocrinology & Metabolism 31 (2020)5. - ISSN 1043-2760 - p. 378 - 389.
atherosclerosis - cardiovascular disease - inflammation - obesity - trained immunity
Obesity, a chronic inflammatory disease, is the most prevalent modifiable risk factor for cardiovascular disease. The mechanisms underlying inflammation in obesity are incompletely understood. Recent developments have challenged the dogma of immunological memory occurring exclusively in the adaptive immune system and show that the innate immune system has potential to be reprogrammed. This innate immune memory (trained immunity) is characterized by epigenetic and metabolic reprogramming of myeloid cells following endogenous or exogenous stimulation, resulting in enhanced inflammation to subsequent stimuli. Trained immunity phenotypes have now been reported for other immune and non-immune cells. Here, we provide a novel perspective on the putative role of trained immunity in mediating the adverse cardiovascular effects of obesity and highlight potential translational pathways.
HILPDA Uncouples Lipid Droplet Accumulation in Adipose Tissue Macrophages from Inflammation and Metabolic Dysregulation
Dierendonck, Xanthe A.M.H. van; Rosa Rodriguez, Montserrat A. de la; Georgiadi, Anastasia ; Mattijssen, Frits ; Dijk, Wieneke ; Weeghel, Michel van; Singh, Rajat ; Borst, Jan Willem ; Stienstra, Rinke ; Kersten, Sander - \ 2020
Cell Reports 30 (2020)6. - ISSN 2211-1247 - p. 1811 - 1822.e6.
ATGL - fatty acid metabolism - Hilpda - inflammation - lipid droplets - macrophages - obesity
Obesity leads to a state of chronic, low-grade inflammation that features the accumulation of lipid-laden macrophages in adipose tissue. Here, we determined the role of macrophage lipid-droplet accumulation in the development of obesity-induced adipose-tissue inflammation, using mice with myeloid-specific deficiency of the lipid-inducible HILPDA protein. HILPDA deficiency markedly reduced intracellular lipid levels and accumulation of fluorescently labeled fatty acids. Decreased lipid storage in HILPDA-deficient macrophages can be rescued by inhibition of adipose triglyceride lipase (ATGL) and is associated with increased oxidative metabolism. In diet-induced obese mice, HILPDA deficiency does not alter inflammatory and metabolic parameters, despite markedly reducing lipid accumulation in macrophages. Overall, we find that HILPDA is a lipid-inducible, physiological inhibitor of ATGL-mediated lipolysis in macrophages and uncouples lipid storage in adipose tissue macrophages from inflammation and metabolic dysregulation. Our data question the contribution of lipid droplet accumulation in adipose tissue macrophages in obesity-induced inflammation and metabolic dysregulation.
Mice Deficient in the IL-1β Activation Genes Prtn3, Elane, and Casp1 Are Protected Against the Development of Obesity-Induced NAFLD
Mirea, Andreea Manuela ; Stienstra, Rinke ; Kanneganti, Thirumala Devi ; Tack, Cees J. ; Chavakis, Triantafyllos ; Toonen, Erik J.M. ; Joosten, Leo A.B. - \ 2020
Inflammation Research 43 (2020). - ISSN 0360-3997 - p. 1054 - 1064.
IL-1 beta - inflammation - neutrophil serine proteases - obesity
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Inflammatory pathways contribute to disease pathogenesis; however, regulation of the underlying mechanism is not completely understood. IL-1β, a pro-inflammatory cytokine, participates in the development and progression of NAFLD. To become bioactive, IL-1β requires enzymatic processing. Mechanisms that activate IL-1β include the classical NLRP3 inflammasome-caspase-1 and the neutrophil serine proteases, neutrophil elastase, and proteinase-3. Several studies have shown that both caspase-1 and the neutrophil serine proteases are important for NAFLD development. However, it is unknown whether these pathways interact and if they have a synergistic effect in promoting NAFLD. In the present study, we developed a novel and unique mouse model by intercrossing caspase-1/11 knockout mice with neutrophil elastase/proteinase-3 double knockout mice. Subsequently, these mice were examined regarding the development of high-fat diet–induced NAFLD. Our results show that mice deficient in caspase-1, neutrophil elastase, and proteinase-3 were protected from developing diet-induced weigh gain, liver steatosis, and adipose tissue inflammation when compared with controls. We conclude that pathways that process pro-IL-1β to bioactive IL-1β play an important role in promoting the development of NAFLD and obesity-induced inflammation. Targeting these pathways could have a therapeutic potential in patients with NAFLD.
Editorial : Diet, Inflammation and Colorectal Cancer
Gessani, Sandra ; Duijnhoven, Fränzel J. Van; Moreno-Aliaga, Maria Jesus - \ 2019
Frontiers in Immunology 10 (2019). - ISSN 1664-3224
colorectal cancer - diet - dietary factors - inflammation - obesity
Interleukin-1α deficiency reduces adiposity, glucose intolerance and hepatic de-novo lipogenesis in diet-induced obese mice
Almog, Tal ; Kandel Kfir, Michal ; Levkovich, Hana ; Shlomai, Gadi ; Barshack, Iris ; Stienstra, Rinke ; Lustig, Yaniv ; Leikin Frenkel, Alicia ; Harari, Ayelet ; Bujanover, Yoram ; Apte, Roni ; Shaish, Aviv ; Harats, Dror ; Kamari, Yehuda - \ 2019
BMJ Open Diabetes Research and Care 7 (2019)1. - ISSN 2052-4897
de novo lipogenesis - glucose intolerance - interleukin-1 - obesity
Objective While extensive research revealed that interleukin (IL)-1β contributes to insulin resistance (IR) development, the role of IL-1α in obesity and IR was scarcely studied. Using control, whole body IL-1α knockout (KO) or myeloid-cell-specific IL-1α-deficient mice, we tested the hypothesis that IL-1α deficiency would protect against high-fat diet (HFD)-induced obesity and its metabolic consequences. Research design and methods To induce obesity and IR, control and IL-1α KO mice were given either chow or HFD for 16 weeks. Glucose tolerance test was performed at 10 and 15 weeks, representing early and progressive stages of glucose intolerance, respectively. Liver and epididymal white adipose tissue (eWAT) samples were analyzed for general morphology and adipocyte size. Plasma levels of adiponectin, insulin, total cholesterol and triglyceride (TG), lipoprotein profile as well as hepatic lipids were analyzed. Expression of lipid and inflammation-related genes in liver and eWAT was analyzed. Primary mouse hepatocytes isolated from control mice were treated either with dimethyl sulfoxide (DMSO) (control) or 20 ng/mL recombinant IL-1α for 24 hours and subjected to gene expression analysis. Results Although total body weight gain was similar, IL-1α KO mice showed reduced adiposity and were completely protected from HFD-induced glucose intolerance. In addition, plasma total cholesterol and TG levels were lower and HFD-induced accumulation of liver TGs was completely inhibited in IL-1α KO compared with control mice. Expression of stearoyl-CoA desaturase1 (SCD1), fatty acid synthase (FASN), elongation of long-chain fatty acids family member 6 (ELOVL6), acetyl-CoA carboxylase (ACC), key enzymes that promote de-novo lipogenesis, was lower in livers of IL-1α KO mice. Treatment with recombinant IL-1α elevated the expression of ELOVL6 and FASN in mouse primary hepatocytes. Finally, mice with myeloid-cell-specific deletion of IL-1α did not show reduced adiposity and improved glucose tolerance. Conclusions We demonstrate a novel role of IL-1α in promoting adiposity, obesity-induced glucose intolerance and liver TG accumulation and suggest that IL-1α blockade could be used for treatment of obesity and its metabolic consequences.
Combined Treatment with L-Carnitine and Nicotinamide Riboside Improves Hepatic Metabolism and Attenuates Obesity and Liver Steatosis
Salic, Kanita ; Gart, Eveline ; Seidel, Florine ; Verschuren, Lars ; Caspers, Martien ; Duyvenvoorde, Wim van; Wong, Kari E. ; Keijer, Jaap ; Bobeldijk-Pastorova, Ivana ; Wielinga, Peter Y. ; Kleemann, Robert - \ 2019
International Journal of Molecular Sciences 20 (2019)18. - ISSN 1661-6596
acylcarnitines - lipid peroxidation - metabolomics - mitochondria - non-alcoholic fatty liver disease - obesity - transcriptomics - β-oxidation
Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for β-oxidation and the TCA cycle, respectively. Ldlr -/-.Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC; 0.4% w/w), nicotinamide riboside (NR; 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (-17%) and hepatic steatosis (-22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.
Sex-Specific Differences in Fat Storage, Development of Non-Alcoholic Fatty Liver Disease and Brain Structure in Juvenile HFD-Induced Obese Ldlr-/-.Leiden Mice
Jacobs, Sophie A.H. ; Gart, Eveline ; Vreeken, Debby ; Franx, Bart A.A. ; Wekking, Lotte ; Verweij, Vivienne G.M. ; Worms, Nicole ; Schoemaker, Marieke H. ; Gross, Gabriele ; Morrison, Martine C. ; Kleemann, Robert ; Arnoldussen, Ilse A.C. ; Kiliaan, Amanda J. - \ 2019
Nutrients 11 (2019)8. - ISSN 2072-6643
juvenile - obesity - sex
BACKGROUND: Sex-specific differences play a role in metabolism, fat storage in adipose tissue, and brain structure. At juvenile age, brain function is susceptible to the effects of obesity; little is known about sex-specific differences in juvenile obesity. Therefore, this study examined sex-specific differences in adipose tissue and liver of high-fat diet (HFD)-induced obese mice, and putative alterations between male and female mice in brain structure in relation to behavioral changes during the development of juvenile obesity. METHODS: In six-week-old male and female Ldlr-/-.Leiden mice (n = 48), the impact of 18 weeks of HFD-feeding was examined. Fat distribution, liver pathology and brain structure and function were analyzed imunohisto- and biochemically, in cognitive tasks and with MRI. RESULTS: HFD-fed female mice were characterized by an increased perigonadal fat mass, pronounced macrovesicular hepatic steatosis and liver inflammation. Male mice on HFD displayed an increased mesenteric fat mass, pronounced adipose tissue inflammation and microvesicular hepatic steatosis. Only male HFD-fed mice showed decreased cerebral blood flow and reduced white matter integrity. CONCLUSIONS: At young age, male mice are more susceptible to the detrimental effects of HFD than female mice. This study emphasizes the importance of sex-specific differences in obesity, liver pathology, and brain function.
Sweet Snacks Are Positively and Fruits and Vegetables Are Negatively Associated with Visceral or Liver Fat Content in Middle-Aged Men and Women
Eekelen, Esther Van; Geelen, Anouk ; Alssema, Marjan ; Lamb, Hildo J. ; Roos, Albert De; Rosendaal, Frits R. ; Mutsert, Rencrossed De - \ 2019
The Journal of Nutrition 149 (2019)2. - ISSN 0022-3166 - p. 304 - 313.
food groups - liver fat - middle-aged men and women - obesity - visceral fat
Visceral adipose tissue (VAT) and hepatic triglyceride content (HTGC) are major risk factors for cardiometabolic diseases. Objective: We aimed to investigate the association of dietary intake of the main food groups with VAT and HTGC in middle-aged men and women. Methods: We used data from the Netherlands Epidemiology of Obesity study, a population-based study including 6671 participants aged 45-65 y at baseline. In this cross-sectional analysis, VAT and HTGC were assessed by magnetic resonance imaging and spectroscopy, respectively, as the primary outcomes. Habitual intake of main food groups (dairy, meat, fish, fruits and vegetables, sweet snacks, and fats and oils) was estimated through the use of a food-frequency questionnaire. We examined associations of intake of different food groups with VAT and HTGC by linear regression analysis stratified by sex and adjusted for age, smoking, education, ethnicity, physical activity, basal metabolic rate, energy-restricted diet, menopausal state, and total energy intake. Results: In women, a 100-g/d higher intake of dairy was associated with 2.0 cm2 less VAT (95% CI: -3.4, -0.7 cm2) and a 0.95-fold lower HTGC (95% CI: 0.90-, 0.99-fold). Moreover, a 100-g/d higher intake of fruit and vegetables was associated with 1.6 cm2 less VAT (95% CI: -2.9, -0.2 cm2) in women. Fruit and vegetables were negatively associated (0.95; 95% CI: 0.91, 1.00) with HTGC, and sweet snacks were positively associated (1.29; 95% CI: 1.03, 1.63). Patterns were weaker but similar in men. Fish intake was not associated with VAT or HTGC and plant-based fat and oil intake were only associated with VAT after adjustment for total body fat. Conclusions: Despite some variation in the strength of the associations between men and women, dietary intake of sweet snacks was positively associated with HTGC, and fruit and vegetable intake were negatively associated with visceral and liver fat content. Prospective studies are needed to confirm these results. The Netherlands Epidemiology of Obesity study is registered at clinicaltrials.gov with identifier NCT03410316. J Nutr 2019;149:304-313.
B Vitamins Can Reduce Body Weight Gain by Increasing Metabolism-related Enzyme Activities in Rats Fed on a High-Fat Diet
Zheng, Ying ; Ma, A. ; Zheng, Ming C. ; Wang, Qiuzhen ; Liang, Hui ; Han, Xiuxia ; Schouten, Evert G. - \ 2018
Current Medical Science 38 (2018)1. - ISSN 2096-5230 - p. 174 - 183.
B vitamins - body weight gain - enzyme activities - obesity - rats
B vitamins are enzyme cofactors that play an important role in energy metabolism. The aim of this study was to elucidate whether B vitamin administration can reduce body weight (BW) gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet. Fifty rats were randomly assigned to one of the following five groups: control group (C), including rats fed on standard rat chow; four treatment groups (HO, HI, H2, and H3), in which rats were fed on a high-fat diet. Rats in the HI group were treated daily with 100 mg/kg BW thiamine (VB1), 100 mg/kg BW riboflavin (VB2), and 250 mg/kg BW niacin (VPP); rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine (VB6), 100 mg/kg BW cobalamin (VB12), and 5 mg/kg BW folate (FA); and rats in the H3 group were treated daily with all of the B vitamins administered to the HI and H2 groups. After 12 weeks, the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the HI and C groups, respectively, which were significantly less than the changes in the HO group (285.2±14.8 g, P<0.05). In the HO group, the plasma total cholesterol (CHO) and triglyceride (TG) levels were 1.59±0.30 mmol/L and 1,55±0.40 mmol/L, respectively, which were significantly greater than those in the HI group (1.19±0.18 mmol/L and 0.76±0.34 mmol/L, respectively, P<0.05). The activities of transketolase (TK), glutathione reductase, and Na+/K+ adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the HO group (P<0.05). Furthermore, the glucose-6-phosphate dehydrogenase, pyruvic acid kinase, and succinate dehydrogenase activities also were increased after treatment with B vitamins. Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats, thus possibly providing potential benefits to humans.
Data and analysis of diet-induced and obesity-associated alterations of gut microbiota of 129S6/Sv and C57BL/6J mice
Xiao, Liang ; Sonne, Si Brask ; Feng, Qiang ; Chen, Ning ; Xia, Zhongkui ; Li, Xiaoping ; Fang, Zhiwei ; Fjære, Even ; Derrien, M.M.N. ; Hugenholtz, F. ; Kleerebezem, M. - \ 2017
Beijing Genome Institute (BGI)
PRJEB10308 - ERP011540 - C57BL/6J mice - 129S6/Sv mice - obesity - high fat feeding - microbiota - indomethacin
High fat feeding rather than obesity drives taxonomical and functional changes in the gut microbiota in mice. It is well known that the microbiota of high fat (HF) diet-induced obese mice differs from that of lean mice, but to what extent this difference reflects the obese state or the diet is unclear. To dissociate changes in the gut microbiota associated with high HF feeding from those associated with obesity, we took advantage of the different susceptibility of C57BL/6JBomTac (BL6) and 129S6/SvEvTac (Sv129) mice to diet-induced obesity and of their different responses to inhibition of cyclooxygenase (COX) activity, where inhibition of COX activity in BL6 mice prevents HF diet-induced obesity, but in Sv129 mice accentuates obesity. Using HiSeq-based whole genome sequencing we identified taxonomic and functional differences in the gut microbiota of the two mouse strains fed regular low fat or HF diets with or without supplementation with the COX-inhibitor, indomethacin. Here we present the sequence assemblies and annotations for those 54 samples, together with the gene catalogue and relevative abundance levels of both genes and OTUs. It is hoped these data can be used for comparison in future studies of a similar design.
Data from: Intestinal Ralstonia pickettii augments glucose intolerance in obesity
Udayappan, Shanthadevi D. ; Kovatcheva-Datchary, Petia ; Bakker, Guido J. ; Havik, Stefan R. ; Herrema, Hilde ; Cani, Patrice D. ; Bouter, Kristien E. ; Belzer, C. ; Witjes, Julia J. ; Vrieze, Anne ; Sonnaville, Noor De; Chaplin, Alice ; Raalte, Daniël H. van; Aalvink, S. ; Dallinga-Thie, Geesje M. ; Heilig, G.H.J. ; Bergström, Göran ; Meij, Suzan Van Der; Wagensveld, Bart A. Van; Hoekstra, Joost B.L. ; Holleman, Frits ; Stroes, Erik S.G. ; Groen, Albert K. ; Bäckhed, Fredrik ; Vos, W.M. de; Nieuwdorp, Max - \ 2017
University of Amsterdam
microbiome - obesity - glucose intolerance - inflammation - Ralstonia pickettii
An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.
Between odours and overeating : behavioural and neurobiological mechanisms of olfactory food-cue reactivity
Zoon, Harriët F.A. - \ 2017
Wageningen University. Promotor(en): Cees de Graaf, co-promotor(en): Sanne Boesveldt. - Wageningen : Wageningen University - ISBN 9789463431675 - 178
geurstoffen - overeten - neurobiologie - voedingsgedrag - reukstimulatie - obesitas - eetlust - overgewicht - buik bypass - verzadigdheid - odours - overeating - neurobiology - feeding behaviour - olfactory stimulation - obesity - appetite - overweight - gastric bypass - satiety
The obesogenic environment we live in is characterized by an abundance of available foods and food cues that tempt us to eat. Throughout our lives we learn to associate these food cues (odours, pictures) with physiological consequences of food consumption. The sense of smell is suggested to be very important for determining food quality, guiding us away from spoilt food and towards rewarding foods. Increased sensitivity to environmental cues of rewarding food, decreased sensitivity to physiological cues of hunger and a decreased ability to control impulses are thought to contribute to overeating and obesity. With the research in this thesis we aimed to elucidate the role of odours in (over)eating, to better understand how sensory food cues and hunger feelings are involved in determining our eating pattern.
We assessed the appetizing effects of exposure to odours signalling food with a certain taste (sweet/savoury) and energy density (high/low). Our findings show that smelling a food odour increases appetite for foods that are similar to the odour, both in terms of taste and energy density. These appetizing effects were present when participants were hungry but also when they had just eaten, indicating a possible role in overeating.
Further, consumption of a high-energy food with a certain taste (sweet/savoury) led to a decrease in liking and wanting of foods with a similar taste and energy density. Next to this, we observed more pronounced changes in early neural processing of pictures of high-energy/sweet food after consumption of a high-energy/sweet meal.
Food preferences and -intake after ambient exposure to odours signalling high-energy food, low-energy food and non-food were not different. Odours did not affect these measures of eating behaviour differently in a hungry or satiated state and in normal-weight or overweight participants.
In a group of patients who underwent Roux-en-Y Gastric Bypass weight-loss surgery, we found a shift in food preferences away from high-fat/high-sugar and towards low-fat/low-sugar foods and altered activation in the frontoparietal neural network during (food) cue processing. After compared to before surgery we also found altered prefrontal neural responses when patients inhibited their responses to pictures of high-energy food. These results suggest that RYGB leads to changes in cognitive control of attention and increased neural inhibitory control over behavioural responses.
In conclusion, odours have a specific appetizing function in the anticipatory phase of eating. They are important in determining the taste quality and energy-density and may be involved in the selection of foods for macronutrient regulation. Orthonasal odours should be used to guide food selection towards a healthier eating pattern.
Endocannabinoids derived from n-3 PUFAs - Formation, release and possible roles in inflammation and obesity
Wang, Ya - \ 2017
Wageningen University. Promotor(en): R.F. Witkamp, co-promotor(en): J. Meijerink; J.-P. Vincken. - Wageningen : Wageningen University - ISBN 9789463432016 - 195
polyunsaturated fats - health promotion - obesity - inflammation - cannabinoids - neurology - energy restricted diets - meervoudig onverzadigde vetten - gezondheidsbevordering - obesitas - ontsteking - cannabinoïden - neurologie - energiearme diëten
The fatty acid composition of our daily diet is considered a major determinant of long-term health risk and the development of disease. Several lines of evidence point toward a state of chronic ‘low-grade’ inflammation as an overarching process that is modulated by fatty acids and their different metabolites. Diets rich in omega-3 polyunsaturated fatty acids (PUFAs), among which docosahexaenoic acid (22:6n-3; DHA) have been found to be associated with a reduction of inflammatory activity. However, the mechanisms underlying these immune-modulatory effects of n-3 PUFAs are only partly known. Earlier data from our group and from other labs have provided evidence for an as yet largely unexplored mechanism involving the formation of DHA-derived fatty acid amides. Fatty acid amides (FAAs) are a group of lipids formed from fatty acids and biogenic amines, which are widely occurring in nature. An increasing number of FAAs, including conjugates of fatty acids with neurotransmitters and mono-amines, have been detected as endogenous molecules in different cells and tissues. However, their bioactivities have remained largely unknown so far.
In the first experimental part (chapter 2 and 3) of this thesis, we explored the immune-modulatory profiles of two relatively unknown DHA-derived FAAs conjugates with dopamine and serotonin, respectively. In chapter 2, we enzymatically synthesised the dopamine conjugate of DHA, N-docosahexaenoyl dopamine (DHDA), and demonstrated that DHDA significantly suppressed the production of several mediators involved in (neuro-)inflammation. We showed that these immune-modulatory effects involved the enzyme cyclooxygenase-2 (COX-2), as its gene-expression and (or) production of its metabolite PGE2 were down-regulated by DHDA in both activated macrophages as well as microglia. Additionally, the immune-modulatory activities of DHDA were compared with those of N-arachidonoyl dopamine (NADA) and similar potencies were found in the cell types tested. In chapter 3, we investigated the effects of docosahexaenoyl serotonin (DHA-5-HT), the serotonin conjugate of DHA on inflammatory processes in human PBMCs. By comparing the immune-modulatory potencies of 6 serotonin-conjugates with palmitic acid (PA-5-HT), stearic acid (SA-5-HT), oleic acid (OA-5-HT), arachidonic acid (AA-5-HT), eicosapentaenoic acid (EPA-5-HT) and docosahexaenoic acid (DHA-5-HT), DHA-5-HT turned out to exert the strongest inhibitory effects on the production of IL-17 from ConA-stimulated human PBMCs. Furthermore, DHA-5-HT concentration-dependently inhibited the production of IL-17 and CCL-20, two important Th17 mediators involved in the pathogenesis of IBD. Also, we demonstrated the in vivo presence of N-acyl serotonins in human intestine. Taken together, we revealed the immune-modulatory effects of two n-3 PUFA-derived fatty acid amides with thus far largely unknown functions and showed that these compounds were far more potent than its parent compound DHA. These findings were shown not only for innate inflammatory processes in stimulated mouse macrophages, but were also found to be present in human PBMCs and likely involved the adaptive CD4+ Th17 response.
In order to study the effects of dietary omega-3 fatty acids on endocannabinoid tone in relation to obesity and metabolic health, a parallel-designed, randomized human study was conducted in the second part of the thesis. In this 12 weeks intervention hundred men and women with abdominal obesity were assigned to either a Western type energy restricted (ER) diet, a Targeted ER diet or a control group. The two ER diet groups were both subjected to energy restriction but their diets differed in nutrient composition. The traditional, more Western-style diet (Western ER diet) included both saturated as well as unsaturated fats, whereas the Targeted ER diet was amongst others enriched with monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). This intervention resulted in significant weight loss and significant improvements of metabolic parameters in both energy restriction (ER) dietary intervention groups. In chapter 4, we revealed that the two weight loss regimes (ER-diets) with different fatty acid composition did not significantly affect fasting peripheral levels of AEA and 2-AG in both plasma and abdominal adipose tissues. By contrast, plasma DHEA was found to be significantly decreased in the Western ER group compared with the Targeted ER group. Additionally, circulating EC-related compounds DHEA, DHAGly, PEA and SEA were significantly decreased in the Western ER diet group after intervention. Furthermore, decreased levels of DHEA were positively associated with body weight reduction. In chapter 5, by performing a high calorie mixed meal test (MMT) before and after the intervention, we found that postprandial AEA and 2-AG levels were significantly reduced in the targeted ER group upon the intervention. By contrast, the DHA-derived compounds DHEA and DHAGly showed a significant increase in the Targeted ER group after 12 weeks of intervention. Additionally, all measured endocannabinoids and related compounds, with the exception of 2-AG, showed a similar characteristic time curve in response to the MMT, with EC levels reaching their highest concentration as early as 5 minutes after food intake (T=10min in experiment).
In conclusion, we showed here that two largely unknown amidated DHA conjugates are more potent mediators of inflammatory processes than their parent compound DHA. These findings support our previously proposed idea that DHA-derived FAAs play a role in the underlying mechanism of the beneficial health effects of DHA. We further uncovered that a combination of ER and n-3 PUFAs in the diet alters the postprandial endocannabinoid tone. Given the fact that the endocannabinoid system (ECS) plays an important role in both the central and peripheral regulation of food intake and energy homeostasis, these findings provide new insights in the potentially mechanisms involved in an over-activated endocannabinoid system during obesity.
External cues challenging the internal appetite control system—Overview and practical implications
Bilman, Els ; Kleef, Ellen van; Trijp, Hans van - \ 2017
Critical Reviews in Food Science and Nutrition 57 (2017)13. - ISSN 1040-8398 - p. 2825 - 2834.
Food environment - food intake - obesity - satiation - satiety
Inadequate regulation of food intake plays an important role in the development of overweight and obesity, and is under the influence of both the internal appetite control system and external environmental cues. Especially in environments where food is overly available, external cues seem to override and/or undermine internal signals, which put severe challenges on the accurate regulation of food intake. By structuring these external cues around five different phases in the food consumption process this paper aims to provide an overview of the wide range of external cues that potentially facilitate or hamper internal signals and with that influence food intake. For each of the five phases of the food consumption process, meal initiation, meal planning, consumption phase, end of eating episode and time till next meal, the most relevant internal signals are discussed and it is explained how specific external cues exert their influence.
How to measure health improvement? : assessment of subtle shifts in metabolic phenotype
Fazelzadeh, Parastoo - \ 2017
Wageningen University. Promotor(en): A.H. Kersten; J.P.M. van Duynhoven, co-promotor(en): M.V. Boekschoten. - Wageningen : Wageningen University - ISBN 9789463430739 - 187
health promotion - improvement - measurement - metabolic profiling - elderly - obesity - microarrays - rna - peripheral blood mononuclear cells - gezondheidsbevordering - verbetering - meting - metabolische profilering - ouderen - obesitas - microarrays - rna - perifere mononucleaire bloedcellen
Human health is impacted by a complex network of interactions between biological pathways, mechanisms, processes, and organs, which need to be able to adapt to a continuously changing environment to maintain health. This adaptive ability is called ‘phenotypic flexibility’. It is thought that health is compromised and diseases develop when these adaptive processes fail. As the product of interactions between several factors such as genetic makeup, diet, lifestyle, environment and the gut microbiome, the ‘metabolic phenotype’ provides a readout of the metabolic state of an individual. Understanding these relationships will be one of a major challenges in nutrition and health research in the next decades. To address this challenge, the development of high-throughput omics tools combined with the application of elaborate statistical analyses will help characterize the complex relationship of (bio) chemicals in human systems and their interaction with other variables including environment and lifestyle to produce the measured phenotype. An important aim of this thesis was to identify phenotype shifts by looking at effect of prolonged resistance-type exercise training on skeletal muscle tissue in older subjects and the possible shift toward the features of younger subjects as a reference for a healthier phenotype. A second aim was to identify phenotype shifts by looking at the response to a challenge in obese subjects and the possible shift toward lean subjects as a reference for a healthier phenotype.
Chapter 2 and 3 of this thesis show how the significant remaining plasticity of ageing skeletal muscle can adapt to resistance-type exercise training. The data indicate that frail and healthy older subjects have two distinct phenotypes according to the skeletal muscle tissue metabolite profiles and that exercise training shifts aged muscle towards a younger phenotype. We showed that the effect of exercise on amino acid derived acylcarnitines (AAAC’s) in older subjects points towards decreased branched chain amino acid catabolism, likely due to compromised activation of the branched chain α-keto acid hydrogenase (BCKDH) complex. Furthermore, we found that the protocadherin gamma gene cluster might be involved in aged-muscle denervation and re-innervation. Finally, plasma was found to be a poor indicator of muscle metabolism, emphasizing the need for direct assessment of metabolites in muscle tissue.
Chapter 4 of this thesis examines whether a mixed meal challenge response provides a readout for a shift in phenotype upon weight loss in obese male subjects. We concluded that weight loss moderately affects the mixed meal challenge response of both plasma metabolome and transcriptome of peripheral blood mononuclear cells in obese subjects. Measurements at the fasted and postprandial state also provide us with a different type of information.
In Chapter 5 it is demonstrated that the global testing of pathways could provide a concise summary of the multiple univariate testing approach used in Chapter 4. In Chapter 6 it is discussed how the findings of this thesis increase our understanding of how to measure phenotypic flexibility as a proxy of health. In this thesis it is shown that the correlations between tissue and plasma metabolites are rather weak, emphasising the need to perform organ-specific studies. Availability of less invasive/painful sampling techniques and the use of small amounts of tissue would enable larger scale human studies on adipose tissue and skeletal muscle to more accurately define phenotypical shifts due to diet or lifestyle interventions. With respect to the assessment of phenotypical flexibility by omics approaches, significant complications can be expected in trying to relate plasma metabolism to PBMC gene expression. Organ-focussed approaches that integrate multiple omics levels using system biology approaches are considered to be a lot more promising.
Food-grade Micro-encapsulation Systems that May Induce Satiety via Delayed Lipolysis: A Review
Corstens, M.N. ; Berton-Carabin, C.C. ; Vries, R.J. de; Troost, F.J. ; Masclee, A.A.M. ; Schroen, C.G.P.H. - \ 2017
Critical Reviews in Food Science and Nutrition 57 (2017)10. - ISSN 1040-8398 - p. 2218 - 2244.
In vitro digestion - Ileal brake - emulsion - Food - obesity
The increasing prevalence of overweight and obesity requires new, effective prevention and treatment strategies. One approach to reduce energy intake is by developing novel foods with increased satiating properties, which may be accomplished by slowing down lipolysis to deliver substrates to the ileum, thereby enhancing natural gut-brain signalling pathways of satiety that are normally induced by meal intake. To develop slow release food additives, their processing in the gastrointestinal tract has to be understood; therefore, we start from a general description of the digestive system and relate that to in vitro modelling, satiety and lipolytic mechanisms. The effects of physicochemical lipid composition, encapsulation matrix and interfacial structure on lipolysis are emphasized. We give an overview of techniques and materials used, and discuss partitioning, which may be a key factor for encapsulation performance. Targeted release capsules that delay lipolysis form a real challenge because of the high efficiency of the digestive system; hardly any proof was found that intact orally ingested lipids can be released in the ileum and thereby induce satiety. We expect that this challenge could be tackled with structured o/w-emulsion-based systems that have some protection against lipase, e.g., by hindering bile salt adsorption and/or delaying lipase diffusion.