RESUMEN
Background: Interesterification is an industrial processing technique used widely where hard fats are essential for functionality and consumer acceptability, e.g. margarines and lower fat spreads. Objective: The aim of this study was to compare acute cardiovascular effects of functionally equivalent spreads (similar solid fat content) made with interesterified (IE) or non-IE palm-based fats, or spreadable butter. Methods: A randomised, controlled, 4-armed crossover, double-blind study (25 men, 25 women; 35-75 years; healthy; mean BMI 24.5, SD 3.8), compared effects of mixed nutrient meals containing 50 g fat from functionally equivalent products [IE spread, non-IE spread and spreadable butter (SB), with rapeseed oil (RO) as a reference treatment: with 16.7%, 27.9%, 19.3% and 4% palmitic acid, respectively] on 8 h postprandial changes in plasma triacylglycerol (TAG) and endothelial dysfunction (flow-mediated dilatation; FMD). Circulating reactive oxygen species (estimated using a neutrophil oxidative burst assay), glucose, insulin, NEFA, lipoprotein particle profiles, inflammatory markers (glycoprotein acetylation (Glyc-A) and IL-6), and biomarkers of endotoxemia were measured. Results: Postprandial plasma TAG concentrations after test meals were similar. However following RO versus the 3 spreads, there were significantly higher postprandial apolipoprotein B concentrations, and small HDL and LDL particle concentrations, and lower postprandial extra-large, large, and medium HDL particle concentrations, as well as smaller average HDL and LDL particle sizes. There were no differences following IE compared to the other spreads. Postprandial FMD% did not decrease after high-fat test meals, and there were no differences between treatments. Postprandial serum IL-6 increased similarly after test meals, but RO provoked a greater increase in postprandial concentrations of glycoprotein acetyls (GlycA), as well as 8 h sCD14, an endotoxemia marker. All other postprandial outcomes were not different between treatments. Conclusions: In healthy adults, a commercially-available IE-based spread did not evoke a different postprandial triacylglycerol, lipoprotein subclass, oxidative stress, inflammatory or endotoxemic response to functionally-equivalent, but compositionally-distinct alternative spreads. Clinical trial registry number: NCT03438084 (https://ClinicalTrials.gov).
Asunto(s)
Endotoxemia , Ácido Palmítico , Adulto , Masculino , Humanos , Femenino , Grasas de la Dieta , Interleucina-6 , Triglicéridos , Mantequilla , Lipoproteínas , Glicoproteínas , Periodo Posprandial , Estudios CruzadosRESUMEN
Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.
Asunto(s)
Microbioma Gastrointestinal , Probióticos , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Metabolismo de los Lípidos , Aumento de Peso , Probióticos/farmacología , Probióticos/uso terapéutico , Hígado/metabolismo , Triglicéridos , ARN Mensajero/metabolismo , ARN Mensajero/farmacología , Ratones Endogámicos C57BL , Ácidos y Sales Biliares/metabolismoRESUMEN
SCOPE: Lipopolysaccharides and their transporters, LBP and sCD14, are involved in systemic inflammation following a high-fat diet. Natural emulsifiers such as soy lecithin, rich in soybean polar lipids (SPL), are often used by the food industry but little is known about effects of associating SPL with different oils. METHODS AND RESULTS: Thus, this study investigates the effects of 4 weeks feeding of palm (P) or rapeseed (R) oil-enriched diets with or without SPL in mice, on white adipose tissue (WAT) inflammation, on ileum permeability, and on microbiota composition. When SPL are associated with rapeseed oil, a greater gene expression of leptin and inflammation in WAT is observed compared to P-SPL. In ileum, R-SPL group results in a lower expression of TLR4, IAP that detoxify bacterial LPS and tight junction proteins than R group. In turn, the gene expression of Reg3ß and Reg3γ, which have antimicrobial activity, is higher in ileum of R-SPL group than in R group. SPL in rapeseed oil increases specific bacterial species belonging to Lachnospiraceae, Alistipes, and Bacteroidales. CONCLUSION: The incorporation of SPL in a diet with rapeseed oil exerts differential effect on WAT and ileum, with respectively an inflammation of WAT and an antimicrobial activity in ileum, associated with specific microbiota changes.
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Antiinfecciosos , Dieta Alta en Grasa , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Lecitinas , Aceite de Brassica napus/farmacología , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco , Inflamación/metabolismo , Glycine max , Íleon/metabolismo , Antiinfecciosos/farmacologíaRESUMEN
This study evaluates the capacity of a bread enriched with fermentable dietary fibres to modulate the metabolism and nutrients handling between tissues, gut and peripheral, in a context of overfeeding. Net fluxes of glucose, lactate, urea, short chain fatty acids (SCFA), and amino acids were recorded in control and overfed female mini-pigs supplemented or not with fibre-enriched bread. SCFA in fecal water and gene expressions, but not protein levels or metabolic fluxes, were measured in muscle, adipose tissue, and intestine. Fibre supplementation increased the potential for fatty acid oxidation and mitochondrial activity in muscle (acox, ucp2, sdha and cpt1-m, p < 0.05) as well as main regulatory transcription factors of metabolic activity such as pparα, pgc-1α and nrf2. All these features were associated with a reduced muscle fibre cross sectional area, resembling to controls (i.e., lean phenotype). SCFA may be direct inducers of these cross-talk alterations, as their feces content (+52%, p = 0.05) was increased in fibre-supplemented mini-pigs. The SCFA effects could be mediated at the gut level by an increased production of incretins (increased gcg mRNA, p < 0.05) and an up-regulation of SCFA receptors (increased gpr41 mRNA, p < 0.01). Hence, consumption of supplemented bread with fermentable fibres can be an appropriate strategy to activate muscle energy catabolism and limit the establishment of an obese phenotype.
Asunto(s)
Tejido Adiposo/metabolismo , Fibras de la Dieta/administración & dosificación , Metabolismo Energético/efectos de los fármacos , Músculo Esquelético/metabolismo , Hipernutrición/metabolismo , Aminoácidos/metabolismo , Animales , Pan , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles/metabolismo , Heces/química , Femenino , Alimentos Fermentados , Glucosa/metabolismo , Incretinas/metabolismo , Intestinos/metabolismo , Ácido Láctico/metabolismo , Porcinos , Porcinos Enanos , Urea/metabolismoRESUMEN
SCOPE: Synthetic emulsifiers have recently been shown to promote metabolic syndrome and considerably alter gut microbiota. Yet, data are lacking regarding the effects of natural emulsifiers, such as plant lecithins rich in essential α-linolenic acid (ALA), on gut and metabolic health. METHODS AND RESULTS: For 5 days, male Swiss mice are fed diets containing similar amounts of ALA and 0, 1, 3, or 10% rapeseed lecithin (RL) or 10% soy lecithin (SL). Following an overnight fast, they are force-fed the same oil mixture and euthanized after 90 minutes. The consumption of lecithin significantly increased fecal levels of the Clostridium leptum group (p = 0.0004), regardless of origin or dose, without altering hepatic or intestinal expression of genes of lipid metabolism. 10%-RL increased ALA abundance in plasma triacylglycerols at 90 minutes, reduced cecal bile acid hydrophobicity, and increased their sulfatation, as demonstrated by the increased hepatic RNA expression of Sult2a1 (p = 0.037) and cecal cholic acid-7 sulfate (CA-7S) concentration (p = 0.05) versus 0%-lecithin. CONCLUSION: After only 5 days, nutritional doses of RL and SL modified gut bacteria in mice, by specifically increasing C. leptum group. RL also increased postprandial ALA abundance and induced beneficial modifications of the bile acid profile. ALA-rich lecithins, especially RL, may then appear as promising natural emulsifiers.
Asunto(s)
Ácidos y Sales Biliares/análisis , Brassica napus , Microbioma Gastrointestinal/efectos de los fármacos , Glycine max , Lecitinas/administración & dosificación , Metabolismo de los Lípidos/efectos de los fármacos , Animales , Ácidos y Sales Biliares/metabolismo , Lípidos/sangre , Masculino , Ratones , Periodo Posprandial/fisiología , Ácido alfa-Linolénico/administración & dosificaciónRESUMEN
Circulating levels of lipopolysaccharide-binding protein (LBP) and soluble cluster of differentiation 14 (sCD14) are recognized as clinical markers of endotoxemia. In obese men, postprandial endotoxemia is modulated by the amount of fat ingested, being higher compared to normal-weight (NW) subjects. Relative variations of LBP/sCD14 ratio in response to overfeeding are also considered important in the inflammation set-up, as measured through IL-6 concentration. We tested the hypothesis that postprandial LBP and sCD14 circulating concentrations differed in obese vs. overweight and NW men after a fat-rich meal. We thus analyzed the postprandial kinetics of LBP and sCD14 in the context of two clinical trials involving postprandial tests in normal-, over-weight and obese men. In the first clinical trial eight NW and 8 obese men ingested breakfasts containing 10 vs. 40 g of fat. In the second clinical trial, 18 healthy men were overfed during 8 weeks. sCD14, LBP and Il-6 were measured in all subjects during 5 h after test meal. Obese men presented a higher fasting and postprandial LBP concentration in plasma than NW men regardless of fat load, while postprandial sCD14 was similar in both groups. Irrespective of the overfeeding treatment, we observed postprandial increase of sCD14 and decrease of LBP before and after OF. In obese individuals receiving a 10 g fat load, whereas IL-6 increased 5h after meal, LBP and sCD14 did not increase. No direct association between the postprandial kinetics of endotoxemia markers sCD14 and LBP and of inflammation in obese men was observed in this study.
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Peso Corporal , Proteínas Portadoras/sangre , Dieta Alta en Grasa/efectos adversos , Receptores de Lipopolisacáridos/sangre , Glicoproteínas de Membrana/sangre , Sobrepeso/sangre , Periodo Posprandial , Proteínas de Fase Aguda/genética , Adulto , Biomarcadores/sangre , Proteínas Portadoras/genética , Estudios Cruzados , Humanos , Receptores de Lipopolisacáridos/genética , Masculino , Glicoproteínas de Membrana/genética , Obesidad/sangreRESUMEN
(1) Background: Nutrition is a major lifestyle factor that can prevent the risk of cognitive impairment and dementia. Diet-induced metabolic endotoxemia has been proposed as a major root cause of inflammation and these pathways emerge as detrimental factors of healthy ageing. The aim of this paper was to update research focusing on the relationship between a fat-rich diet and endotoxemia, and to discuss the potential role of endotoxemia in cognitive performances. (2) Methods: We conducted a non-systematic literature review based on the PubMed database related to fat-rich meals, metabolic endotoxemia and cognitive disorders including dementia in humans. A total of 40 articles out of 942 in the first screening met the inclusion criteria. (3) Results: Evidence suggested that a fat-rich diet, depending on its quality, quantity and concomitant healthy food components, could influence metabolic endotoxemia. Since only heterogeneous cross-sectional studies are available, it remains unclear to what extent endotoxemia could be associated or not with cognitive disorders and dementia. (4) Conclusions: A fat-rich diet has the capability to provide significant increases in circulating endotoxins, which highlights nutritional strategies as a promising area for future research on inflammatory-associated diseases. The role of endotoxemia in cognitive disorders and dementia remains unclear and deserves further investigation.
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Bacterias/metabolismo , Envejecimiento Cognitivo/psicología , Disfunción Cognitiva/etiología , Grasas de la Dieta/efectos adversos , Endotoxemia/etiología , Microbioma Gastrointestinal , Adulto , Factores de Edad , Anciano , Cognición , Disfunción Cognitiva/sangre , Disfunción Cognitiva/microbiología , Disfunción Cognitiva/psicología , Endotoxemia/sangre , Endotoxemia/microbiología , Endotoxemia/psicología , Femenino , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Valor Nutritivo , Pronóstico , Medición de Riesgo , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Identifying the mechanisms involved in the pathogenesis of Alzheimer's disease (AD) remains crucially important. Chronic age-related low-grade inflammation is considered to be one such mechanism, although its causes are unclear. Lipopolysaccharide (LPS)-type endotoxins, a major component of the outer membrane of Gram-negative bacteria, are known as potent pro-inflammatory molecules. Therefore, we hypothesized that greater exposure to circulating LPS, potentially mediated by the inflammatory pathway, would be a key step of the onset of AD. OBJECTIVE: The aim of this study was to investigate the link between plasma endotoxin-exposure, inflammation, and AD. METHODS: Applying a nested case-control design, we evaluated the associations among baseline plasma endotoxin-exposure (assessed by measuring LPS-binding protein (LBP) and soluble cluster of differentiation-14 (sCD14) levels), inflammation (assessed by measuring interleukin-6 (IL6) levels), and the odds of developing AD over 12 years. Selected from a population-based cohort, 212 incident cases of AD were matched with 424 controls without dementia with regard to age, gender, and education level. RESULTS: After adjusting for a large set of confounders, including the use of anti-inflammatory drugs, only higher LBP levels were significantly associated with a 30% higher odds of developing AD over 12 years (OR 1.30, 95% CIs [1.07-1.59]), regardless of IL6 levels. CONCLUSION: This large case-control study provides preliminary results concerning plasma endotoxin-exposure among the elderly and suggests that higher LBP levels, an acute-phase reactant involved in the pro-inflammatory response to LPS, are associated with higher odds of developing AD.
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Proteínas de Fase Aguda/genética , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , Proteínas Portadoras/genética , Receptores de Lipopolisacáridos/genética , Glicoproteínas de Membrana/genética , Anciano , Anciano de 80 o más Años , Proteínas Portadoras/sangre , Estudios de Casos y Controles , Femenino , Francia/epidemiología , Humanos , Incidencia , Vida Independiente , Interleucina-6/sangre , Receptores de Lipopolisacáridos/sangre , Masculino , Glicoproteínas de Membrana/sangre , Proyectos Piloto , Población UrbanaRESUMEN
Milk polar lipids (MPL) are specifically rich in milk sphingomyelin (MSM) which represents 24% of MPL. Beneficial effects of MPL or MSM have been reported on lipid metabolism, but information on gut physiology is scarce. Here we assessed whether MPL and MSM can impact tight junction expression. Human epithelial intestinal Caco-2/TC7 cells were incubated with mixed lipid micelles devoid of MSM (Control) or with 0.2 or 0.4 mM of MSM via pure MSM or via total MPL. C57Bl/6 mice received 5 or 10 mg of MSM via MSM or via MPL (oral gavage); small intestinal segments were collected after 4 h. Impacts on tight junction and cytokine expressions were assessed by qPCR; IL-8 and IL-8 murine homologs (Cxcl1, Cxcl2) were analyzed. In vitro, MSM increased tight junction expression (Occludin, ZO-1) vs Control, unlike MPL. However, no differences were observed in permeability assays (FITC-dextran, Lucifer yellow). MSM increased the secretion and gene expression of IL-8 but not of other inflammatory cytokines. Moreover, cell incubation with IL-8 induced an overexpression of tight junction proteins. In mice, mRNA level of Cxcl1 and Cxcl2 in the ileum were increased after gavage with MSM vs NaCl but not with MPL. Altogether, these results suggest a specific action of MSM on intestinal tight junction expression, possibly mediated by IL-8. Our study provides clues to shed light on the beneficial effects of MPL on intestinal functions and supports the need for further mechanistic exploration of the direct vs indirect effects of MSM and IL-8 on the gut barrier.
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Interleucina-8/metabolismo , Lípidos/farmacología , Leche/química , Uniones Estrechas/metabolismo , Animales , Células CACO-2 , Quimiocina CXCL1/genética , Quimiocina CXCL2/genética , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Intestinos/citología , Lípidos/química , Masculino , Ratones Endogámicos C57BL , Esfingomielinas/administración & dosificación , Esfingomielinas/farmacología , Proteínas de Uniones Estrechas/genéticaRESUMEN
SCOPE: Enhanced adiposity and metabolic inflammation are major features of obesity associated with altered gut microbiota and intestinal barrier. How these metabolic outcomes can be impacted by milk polar lipids (MPL), naturally containing 25% of sphingomyelin, is investigated in mice fed a mixed high-fat (HF) diet . METHODS AND RESULTS: Male C57Bl/6 mice receive a HF-diet devoid of MPL (21% fat, mainly palm oil, in chow), or supplemented with 1.1% or 1.6% of MPL (HF-MPL1; HF-MPL2) via a total-lipid extract from butterserum concentrate for 8 weeks. HF-MPL2 mice gain less weight versus HF (p < 0.01). Diets do not impact plasma markers of inflammation but in the liver, HF-MPL2 tends to decrease hepatic gene expression of macrophage marker F4/80 versus HF-MPL1 (p = 0.06). Colonic crypt depth is the maximum in HF-MPL2 (p < 0.05). In cecal microbiota, HF-MPL1 increases Bifidobacterium animalis versus HF (p < 0.05). HF-MPL2 decreases Lactobacillus reuteri (p < 0.05), which correlates negatively with the fecal loss of milk sphingomyelin-specific fatty acids (p < 0.05). CONCLUSION: In mice fed a mixed HF diet, MPL can limit HF-induced body weight gain and modulate gut physiology and the abundance in microbiota of bacteria of metabolic interest. This supports further exploration of how residual unabsorbed lipids reaching the colon can impact HF-induced metabolic disorders.
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Ácidos Grasos/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Lípidos/farmacología , Leche/química , Animales , Dieta Alta en Grasa , Ácidos Grasos/análisis , Heces , Absorción Intestinal , Lípidos/administración & dosificación , Lípidos/análisis , Lípidos/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Esfingomielinas/farmacología , Aumento de Peso/efectos de los fármacosRESUMEN
Obesity and its metabolic complications are characterized by subclinical systemic and tissue inflammation. In rodent models of obesity, inflammation and metabolic impairments are linked with intestinal barrier damage. However, whether intestinal permeability is altered in human obesity remains to be investigated. In a cohort of 122 severely obese and non-obese patients, we analyzed intestinal barrier function combining in vivo and ex vivo investigations. We found tight junction impairments in the jejunal epithelium of obese patients, evidenced by a reduction of occludin and tricellulin. Serum levels of zonulin and LPS binding protein, two markers usually associated with intestinal barrier alterations, were also increased in obese patients. Intestinal permeability per se was assessed in vivo by quantification of urinary lactitol/mannitol (L/M) and measured directly ex vivo on jejunal samples in Ussing chambers. In the fasting condition, L/M ratio and jejunal permeability were not significantly different between obese and non-obese patients, but high jejunal permeability to small molecules (0.4 kDa) was associated with systemic inflammation within the obese cohort. Altogether, these results suggest that intestinal barrier function is subtly compromised in obese patients. We thus tested whether this barrier impairment could be exacerbated by dietary lipids. To this end, we challenged jejunal samples with lipid micelles and showed that a single exposure increased permeability to macromolecules (4 kDa). Jejunal permeability after the lipid load was two-fold higher in obese patients compared to non-obese controls and correlated with systemic and intestinal inflammation. Moreover, lipid-induced permeability was an explicative variable of type 2 diabetes. In conclusion, intestinal barrier defects are present in human severe obesity and exacerbated by a lipid challenge. This paves the way to the development of novel therapeutic approaches to modulate intestinal barrier function or personalize nutrition therapy to decrease lipid-induced jejunal leakage in metabolic diseases. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Diabetes Mellitus Tipo 2/metabolismo , Inflamación/metabolismo , Absorción Intestinal/efectos de los fármacos , Yeyuno/efectos de los fármacos , Lípidos/administración & dosificación , Obesidad/metabolismo , Proteínas de Fase Aguda , Adulto , Anciano , Células CACO-2 , Proteínas Portadoras/sangre , Estudios de Casos y Controles , Toxina del Cólera/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Haptoglobinas , Humanos , Inflamación/complicaciones , Inflamación/fisiopatología , Yeyuno/metabolismo , Yeyuno/fisiopatología , Proteína 2 con Dominio MARVEL/metabolismo , Masculino , Glicoproteínas de Membrana/sangre , Micelas , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/fisiopatología , Ocludina/metabolismo , Permeabilidad , Precursores de Proteínas , Uniones Estrechas/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Postprandial hyperlipemia is recognized as a major cardio-metabolic risk factor, recently linked to the co-absorption of pro-inflammatory lipopolysaccharides with dietary lipids. This causes endotoxemia that is involved in the pathophysiology of obesity and insulin resistance, but to date the impact of food formulation is unknown. We tested a novel concept that endotoxin absorption can be modulated by fat emulsified structure in the meal, and potentially differently in obese vs. lean men. METHODS: In a randomized controlled crossover study, eight normal-weight and eight obese age-matched healthy men ingested two isocaloric, isolipidic breakfasts of identical composition including 40 g of milk fat that was emulsified or unemulsified. Plasma- and chylomicron-endotoxemia and chylomicron-triglycerides were measured during 8 h after breakfast ingestion. RESULTS: After emulsion consumption, parallel to an enhanced chylomicronemia, obese subjects presented an early and sharp increase in chylomicron-endotoxemia at 60 min (P time = 0.02), which was higher than (i) after spread fat in obese subjects (P < 0.05) and (ii) after both spread and emulsified fat in normal-weight subjects (P < 0.05). However in obese subjects, the iAUC of plasma endotoxemia over 8 h was lower after emulsion than after spread fat (P < 0.05) whereas in NW subjects such reduction of plasma LPS-iAUC was not observed (P = 0.67). CONCLUSION: This study provides initial evidence that optimizing fat structure in the meal can be part of a dietary strategy to lower the metabolic impact of postprandial endotoxemia in obese men. TRIAL REGISTRATION: Registered at ClinicalTrials.gov # NCT01249378 on July 13, 2010.
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Grasas de la Dieta/farmacología , Endotoxemia/dietoterapia , Hiperlipoproteinemia Tipo I/dietoterapia , Obesidad/dietoterapia , Adulto , Estudios Cruzados , Endotoxemia/metabolismo , Humanos , Hiperlipoproteinemia Tipo I/metabolismo , Masculino , Obesidad/metabolismo , Periodo PosprandialRESUMEN
Obesity and its related disorders have been associated with the presence in the blood of gut bacteria-derived lipopolysaccharides (LPS). However, the factors underlying this low-grade elevation in plasma LPS, so-called metabolic endotoxemia, are not fully elucidated. We aimed to investigate the effects of Western diet (WD) feeding on intestinal and hepatic LPS handling mechanisms in a rat model of diet-induced obesity (DIO). Rats were fed either a standard chow diet (C) or a Western Diet (WD, 45% fat) for 6 wk. They were either fed ad libitum or pair-fed to match the caloric intake of C rats for the first week, then fed ad libitum for the remaining 5 wk. Six-week WD feeding led to a mild obese phenotype with increased adiposity and elevated serum LPS-binding protein (LBP) levels relative to C rats, irrespective of initial energy intake. Serum LPS was not different between dietary groups but exhibited strong variability. Disrupted ileal mucus secretion and decreased ileal Reg3-γ and -ß gene expression along with high ileal permeability to LPS were observed in WD compared with C-fed rats. Ileal and cecal intestinal alkaline phosphatase (IAP) activity as well as Verrucomicrobia and Bifidobacterium cecal levels were increased in WD-fed rats compared with C-fed rats. WD consumption did not impact mRNA levels of LPS-handling hepatic enzymes. Correlation analysis revealed that ileal passage of LPS, IAP activity, Proteobacteria levels and hepatic aoah gene expression correlated with serum LPS and LBP, suggesting that ileal mucosal defense impairment induced by WD feeding contribute to metabolic endotoxemia.
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Dieta Occidental , Ingestión de Alimentos/fisiología , Endotoxemia/metabolismo , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Animales , Células Cultivadas , Endotoxemia/patología , Conducta Alimentaria , Íleon/patología , Mucosa Intestinal/patología , Masculino , Técnicas de Cultivo de Órganos , Permeabilidad , Ratas , Ratas WistarRESUMEN
Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.
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Proteínas de Fase Aguda/metabolismo , Proteínas Portadoras/metabolismo , Glycine max/química , Aceite de Linaza/farmacología , Glicoproteínas de Membrana/metabolismo , Aceite de Palma/farmacología , Paniculitis/etiología , Animales , Dieta Alta en Grasa , Suplementos Dietéticos , Ácidos Grasos/análisis , Receptores de Lipopolisacáridos/metabolismo , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BLRESUMEN
SCOPE: Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. METHODS AND RESULTS: Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p < 0.05), with larger adipocytes (p < 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p < 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p < 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p < 0.05), and more goblet cells in the colon (p < 0.05). CONCLUSIONS: Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak.
Asunto(s)
Colon/efectos de los fármacos , Emulsionantes/farmacología , Glycine max/química , Células Caliciformes/efectos de los fármacos , Leche/química , Tejido Adiposo Blanco/efectos de los fármacos , Adiposidad/efectos de los fármacos , Animales , Células CACO-2/efectos de los fármacos , Colon/citología , Dieta con Restricción de Grasas , Dieta Alta en Grasa/efectos adversos , Humanos , Lecitinas/química , Lecitinas/farmacología , Lípidos/análisis , Lípidos/química , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Paniculitis/inducido químicamente , Paniculitis/metabolismoRESUMEN
BACKGROUND: Polar lipid (PL) emulsifiers such as milk PLs (MPLs) may affect digestion and subsequent lipid metabolism, but focused studies on postprandial lipemia are lacking. OBJECTIVE: We evaluated the impact of MPLs on postprandial lipemia in mice and on lipid digestion in vitro. METHODS: Female Swiss mice were gavaged with 150 µL of an oil-in-water emulsion stabilized with 5.7 mg of either MPLs or soybean PLs (SPLs) and killed after 1, 2, or 4 h. Plasma lipids were quantified and in the small intestine, gene expression was analyzed by reverse transcriptase-quantitative polymerase chain reaction. Emulsions were lipolyzed in vitro using a static human digestion model; triglyceride (TG) disappearance was followed by thin-layer chromatography. RESULTS: In mice, after 1 h, plasma TGs tended to be higher in the MPL group than in the SPL group (141 µg/mL vs. 90 µg/mL; P = 0.07) and nonesterified fatty acids (NEFAs) were significantly higher (64 µg/mL vs. 44 µg/mL; P < 0.05). The opposite was observed after 4 h with lower TGs (21 µg/mL vs. 35 µg/mL; P < 0.01) and NEFAs (20 µg/mL vs. 32 µg/mL; P < 0.01) in the MPL group compared with the SPL group. This was associated at 4 h with a lower gene expression of apolipoprotein B (Apob) and Secretion Associated, Ras related GTPase 1 gene homolog B (Sar1b), in the duodenum of MPL mice compared with SPL mice (P < 0.05). In vitro, during the intestinal phase, TGs were hydrolyzed more in the MPL emulsion than in the SPL emulsion (decremental AUCs were 1750%/min vs. 180%/min; P < 0.01). MPLs enhance lipid intestinal hydrolysis and promote more rapid intestinal lipid absorption and sharper kinetics of lipemia. CONCLUSIONS: Postprandial lipemia in mice can be modulated by emulsifying with MPLs compared with SPLs, partly through differences in chylomicron assembly, and TG hydrolysis rate as observed in vitro. MPLs may thereby contribute to the long-term regulation of lipid metabolism.
Asunto(s)
Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/farmacología , Lipólisis/efectos de los fármacos , Leche/química , Animales , Emulsionantes , Femenino , Regulación de la Expresión Génica , Intestino Delgado/metabolismo , Lecitinas , Lípidos/química , Ratones , Periodo PosprandialRESUMEN
CONTEXT: Postprandial endotoxemia is a metabolic risk factor, which has been shown to originate from the intestinal absorption of gut lipopolysaccharides (LPS) using nonphysiological high-fat tests. OBJECTIVE: This study aimed to determine whether different realistic fat amounts can modulate postprandial dynamics and handling of LPS by varying postprandial lipidemia in humans of different body mass indices. DESIGN, SETTING, AND PARTICIPANTS: In a randomized, controlled, cross-over study in nutrition research center, eight normal-weight (NW) and eight obese age-matched men, without diabetes nor dyslipidemia, ingested breakfasts containing 10 vs 40 g fat. Blood samples, leukocytes, and chylomicron-rich fractions were obtained during 8 h. Plasma and chylomicron-endotoxemia, plasma LPS transporters (LBP, sCD14) and IL-6, nuclear factor κB (NF-κB) translocation, and IL-6 gene expression of immune cells were measured. MAIN OUTCOME: The postprandial fatty acid handling after ingesting 40 g fat was previously published as primary outcome. The secondary outcomes were inflammatory ones including postprandial endotoxemia, LPS handling, and plasma markers of inflammation after ingesting 10 or 40 g fat. RESULTS: Chylomicronemia increased in all subjects according to ingested fat amount (P < .01), but only obese had higher postprandial endotoxemia after 40 g (P < .05). Obese subject chylomicrons were more enriched with LPS compared with NW (PBMI < .01). We observed neither NF-κB translocation, nor variation of IL-6 expression in leukocytes. In both groups, fat amount did not modify postprandial response of plasma IL-6. However, the area under the curve (AUC) of IL-6 in obese was higher than in NW (P < .05) parallel to higher fasting LPS-binding protein (LBP; P < .05). AUC of IL-6 was correlated with LBP (P < .01). CONCLUSION: Postprandial endotoxemia is modulated by ingested fat amount in obese men. LPS handling in plasma through chylomicrons and LBP seems critical in driving the acute inflammatory response. The pathophysiological importance of repeated postprandial endotoxemia excursions and their contribution to a vicious cycle of LBP-driven low-grade inflammation deserve further investigation in the nutritional management of cardio-metabolic risk prevention.
Asunto(s)
Quilomicrones/sangre , Endotoxemia/sangre , Lipopolisacáridos/sangre , Obesidad/sangre , Periodo Posprandial/fisiología , Proteínas de Fase Aguda , Adulto , Glucemia , Índice de Masa Corporal , Proteínas Portadoras/sangre , Estudios Cruzados , Grasas de la Dieta , Relación Dosis-Respuesta a Droga , Humanos , Insulina/sangre , Masculino , Glicoproteínas de Membrana/sangreRESUMEN
The impacts of high-fat diets (HFDs) on the onset of metabolic endotoxemia and low-grade inflammation are well established in rodent models. However, the dose-effect of dietary lipid intakes on these parameters is not known. We hypothesized that increasing dietary lipid amounts could be linked to parallel increases of endotoxemia, low-grade inflammation, and metabolic and intestinal alterations. Six-week-old male C57BL/6J mice were fed a low-fat diet (LFD, 2.6 wt% of lipids), a moderate HFD (mHFD, 22 wt% of lipids), or a very HFD (vHFD, 45 wt% of lipids) formulated mainly using chow ingredients and milk fat. After 12 weeks, white adipose tissues, liver, intestine, distal colon contents, and plasma were collected. Only vHFD mice significantly increased body weight and fat mass vs LFD mice. This was associated with increases of plasma concentrations of triglycerides, leptin and adiponectin, and liver lipids. No such differences were observed between LFD and mHFD mice. However, mHFD developed metabolic endotoxemia and inflammation, unlike vHFD mice. In turn, vHFD mice showed more goblet cells in all intestine segments vs both other groups and a decrease of Bacteroides-Prevotella in their microbiota vs LFD mice. Finally, mHFD mice colon exhibited a decrease in lactobacilli and in the levels of occludin phosphorylation. Altogether, using complex HFD, no associations were observed between dietary lipid amounts and the magnitude of endotoxemia, inflammation, and physiological alterations developed. These results reveal the impact of the diet composition on intestinal goblet cells and mucus coat, bringing new insights about further consequences on HFD-induced metabolic disorders.
Asunto(s)
Grasas de la Dieta/administración & dosificación , Endotoxemia/fisiopatología , Células Caliciformes/metabolismo , Inflamación/fisiopatología , Adiponectina/sangre , Tejido Adiposo Blanco/metabolismo , Animales , Colon/metabolismo , Dieta con Restricción de Grasas , Dieta Alta en Grasa , Interleucina-6/sangre , Mucosa Intestinal/metabolismo , Intestinos/citología , Leptina/sangre , Lipopolisacáridos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ocludina/metabolismo , Triglicéridos/sangre , Aumento de Peso , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was to investigate, in vitro and in vivo, how skeletal muscle inflammation develops and how in turn it modulates local and systemic insulin sensitivity in different mice models of T2D and in humans, focusing on the role of the chemokine MCP1. Here, we found that skeletal muscle inflammation and macrophage markers are increased and associated with insulin resistance in mice models and humans. In addition, we demonstrated that intra-muscular TNFα expression is exclusively restricted to the population of intramuscular leukocytes and that the chemokine MCP1 was associated with skeletal muscle inflammatory markers in these models. Furthermore, we demonstrated that exposure of C2C12 myotubes to palmitate elevated the production of the chemokine MCP1 and that the muscle-specific overexpression of MCP1 in transgenic mice induced the local recruitment of macrophages and altered local insulin sensitivity. Overall our study demonstrates that skeletal muscle inflammation is clearly increased in the context of T2D in each one of the models we investigated, which is likely consecutive to the lipotoxic environment generated by peripheral insulin resistance, further increasing MCP1 expression in muscle. Consequently, our results suggest that MCP1-mediated skeletal muscle macrophages recruitment plays a role in the etiology of T2D.
Asunto(s)
Quimiocina CCL2/fisiología , Resistencia a la Insulina/inmunología , Macrófagos/inmunología , Músculo Esquelético/inmunología , Miositis/inmunología , Animales , Línea Celular , Movimiento Celular , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Ratones Transgénicos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Miositis/metabolismoRESUMEN
Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.