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1.
Nutrients ; 15(16)2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37630732

RESUMEN

The microbiota gut-brain axis (mGBA) is an important contributor to mental health and neurological and mood disorders. Lipopolysaccharides (LPS) are endotoxins that are components of Gram-negative bacteria cell walls and have been widely shown to induce both systemic and neuro-inflammation. Flaxseed (Linum usitatissimum) is an oilseed rich in fibre, n3-poly-unsaturated fatty acid (alpha-linolenic acid (ALA)), and lignan, secoisolariciresinol diglucoside, which all can induce beneficial effects across varying aspects of the mGBA. The objective of this study was to determine the potential for dietary supplementation with flaxseed or flaxseed oil to attenuate LPS-induced inflammation through modulation of the mGBA. In this study, 72 5-week-old male C57Bl/6 mice were fed one of three isocaloric diets for 3 weeks: (1) AIN-93G basal diet (BD), (2) BD + 10% flaxseed (FS), or (3) BD + 4% FS oil (FO). Mice were then injected with LPS (1 mg/kg i.p) or saline (n = 12/group) and samples were collected 24 h post-injection. Dietary supplementation with FS, but not FO, partially attenuated LPS-induced systemic (serum TNF-α and IL-10) and neuro-inflammation (hippocampal and/or medial prefrontal cortex IL-10, TNF-α, IL-1ß mRNA expression), but had no effect on sickness and nest-building behaviours. FS-fed mice had enhanced fecal microbial diversity with increased relative abundance of beneficial microbial groups (i.e., Lachnospiraceae, Bifidobacterium, Coriobacteriaceae), reduced Akkermansia muciniphila, and increased production of short-chain fatty acids (SCFAs), which may play a role in its anti-inflammatory response. Overall, this study highlights the potential for flaxseed to attenuate LPS-induced inflammation, in part through modulation of the intestinal microbiota, an effect which may not be solely driven by its ALA-rich oil component.


Asunto(s)
Lino , Microbioma Gastrointestinal , Masculino , Animales , Ratones , Aceite de Linaza/farmacología , Lipopolisacáridos , Interleucina-10 , Eje Cerebro-Intestino , Factor de Necrosis Tumoral alfa , Dieta
2.
J Nutr Biochem ; 98: 108818, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34271098

RESUMEN

Gut microbial processing of dietary flaxseed (FS) contributes to its health benefits, but the relative effects of its bioactive components (lignans, omega-3 fatty acids, fiber) on the microbiota are unclear. We investigated the gut microbial compositional and functional responses to whole FS and its isolated components, FS oil (FSO) and secoisolariciresinol diglucoside (SDG) (precursor to microbial-derived enterolignans) to help understand their contribution to whole FS benefits. Cecum content and fecal samples were collected from C57BL/6 female mice fed a basal diet (AIN93G) or isocaloric diets containing 10% FS or 10% FS-equivalent amounts of FSO or SDG for 21 days. Cecal and fecal microbiota composition and predicted genomic functions, and their relationship with serum enterolignans were evaluated. Only FS modified the community structure. Shared- and diet-specific enriched taxa and functions were identified. Carbohydrate and protein processing functions were enriched in FS mice, and there was a positive correlation between select enriched taxa, encompassing fiber degraders and SDG metabolizers, and serum enterolignans. This was not observed in mice receiving isolated FSO and SDG, suggesting that FS fiber supports SDG microbial metabolism. In conclusion, the cooperative activities of a diverse microbiota are necessary to process FS components and, when administered at the amount present in FS, these components may act together to affect SDG-derived enterolignans production. This has implications for the use of FS, FSO and SDG in clinical practice.


Asunto(s)
Lino/química , Microbioma Gastrointestinal/efectos de los fármacos , Lignanos/farmacología , Aceite de Linaza/farmacología , Animales , Butileno Glicoles/farmacología , Ciego/metabolismo , Ciego/microbiología , Dieta/métodos , Fibras de la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Heces/microbiología , Femenino , Glucósidos/farmacología , Ratones , Ratones Endogámicos C57BL
3.
Nutrition ; 91-92: 111388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34298481

RESUMEN

OBJECTIVES: Chronic low-grade inflammation in obesity is partly driven by inflammatory cross talk between adipocytes and interferon-γ-secreting CD4+ T-helper (Th)1 cells, a process we have shown may be mitigated by long-chain (LC) ω-3 polyunsaturated fatty acids (PUFAs). Our objective was to study pivotal mediators of interactions between Th1 cells and adipocytes as potential mechanisms underlying the antiinflammatory effects of LC ω-3 PUFAs. METHODS: Using an in vitro model, 3T3-L1 adipocytes were cocultured with purified splenic CD4+ T cells from C57BL/6 mice consuming one of two isocaloric high-fat (HF) diets (60% kcal fat), containing either 41.2% kcal from lard + 18.7% kcal from corn oil (control, HF) or 41.2% kcal from lard + 13.4% kcal from corn oil + 5.3% kcal from fish oil (HF+FO). Cocultures were stimulated for 48 h with lipopolysaccharide (10 ng/mL). RESULTS: Compared with HF cocultures, HF+FO reduced Th1-cell markers (including secreted interferon-γ) and increased Th2-cell markers, consistent with reduced expression of genes related to major histocompatibility complex II (P < 0.05). HF+FO also blunted markers of priming and activity of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome (P < 0.05). In confirmatory work, 3T3-L1 adipocyte pretreatment with the LC ω-3 PUFA docosahexaenoic acid (100 µM, 24 h) blunted interferon-γ-induced (5 ng/mL, 24 h) expression of genes related to major histocompatibility complex II and priming and activity markers of the NLRP3 inflammasome compared with control (P < 0.05). CONCLUSIONS: Inflammatory interactions between CD4+ T cells and adipocytes may provide a target for LC ω-3 PUFAs to mitigate obesity-associated inflammation.


Asunto(s)
Ácidos Grasos Omega-3 , Inflamasomas , Adipocitos , Tejido Adiposo , Animales , Técnicas de Cocultivo , Dieta Alta en Grasa , Ácidos Grasos Omega-3/farmacología , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Obesidad/tratamiento farmacológico , Células TH1
4.
J Nutr Biochem ; 95: 108763, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33965532

RESUMEN

Obesity is associated with inflammation and has been shown to increase breast cancer severity. The objective of this study was to examine the effect of fish oil (FO) supplementation in obesity-associated mammary tumorigenesis in the MMTV-neu(ndl)-YD5 mouse model of human epidermal growth factor receptor-2 positive BC. Female mice were fed one of three diets for 16 weeks: i) high fat diet [HF, % kacl: 41.2% lard, 18.7% corn oil (CO)], ii) an isocaloric HF plus menhaden FO diet (HF+FO, % kcal: 41.2 lard, 13.4% CO, 5.3% FO), iii) low fat diet (LF, % kcal: 4.7% lard, 6% CO). HF mice had increased body weight, visceral adipose weight and serum hormone concentrations (increased leptin and resistin; decreased adiponectin) versus LF, which was attenuated in the HF+FO group versus HF (P<.05). Compared to HF, tumor onset was delayed in HF+FO and LF mice (P<0.05). Compared to HF, HF+FO reduced mammary tumor multiplicity (-27%), tumor weight (-46%) and total tumor volume (-50%) (P<0.05). Additionally, HF+FO reduced mammary tumor multiplicity (-33%), tumor weight (-39%) and total tumor volume (-60%) versus LF. HF+FO improved mammary tumor apoptosis status with increased expression of pro-apoptotic Bad and decreased expression of anti-apoptotic Bcl-xLmediators versus HF (P<0.05). Additionally, HF+FO decreased tumor protein expression of activated Akt, NFκB p65 and STAT3, versus HF (P<0.05). Tumor mRNA expression of inflammatory mediators TNFα, IL-6 and leptin were reduced in HF+FO, whereas IL-10 expression was increased compared to HF (P<0.05). Collectively these results demonstrate the efficacy of FO supplementation for improving obesity-associated breast cancer outcomes.


Asunto(s)
Apoptosis/efectos de los fármacos , Aceites de Pescado/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inflamación/tratamiento farmacológico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Obesidad/inducido químicamente , Tejido Adiposo/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Neoplasias de la Mama , Línea Celular Tumoral , Suplementos Dietéticos , Ácidos Grasos/química , Femenino , Aceites de Pescado/administración & dosificación , Humanos , Glándulas Mamarias Animales/química , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Distribución Aleatoria , Receptor ErbB-2
5.
Nutrients ; 13(3)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652785

RESUMEN

Cooked common beans (Phaseolus vulgaris) improve intestinal health in lean mice and attenuate intestinal dysbiosis and inflammation when consumed concurrent with obesity development. We determined the effects of a high-fat (HF) bean supplemented diet in mice with established obesity (induced by 12 weeks of HF diet (60% fat as kcal)) compared to obese mice consuming a HF or low-fat (LF) weight loss control diet. Obese C57BL/6 male mice remained consuming HF for eight weeks or were randomly switched from HF to an isocaloric HF with 15.7% cooked navy bean powder diet (HFàHFB) or LF (11% fat as kcal; HFàLF) (n = 12/group). HFàHFB improved the obese phenotype, including (i) fecal microbiome (increased Prevotella, Akkermansia muciniphila, and short-chain fatty acid levels), (ii) intestinal health (increased ZO-1, claudin-2, Muc2, Relmß, and Reg3γ expression), and (iii) reduced adipose tissue (AT) inflammatory proteins (NFκBp65, STAT3, IL-6, MCP-1, and MIP-1α), versus HF (p < 0.05). Conversely, HFàLF reduced body weight and circulating hormones (leptin, resistin, and PAI-1) versus HF and HFàHFB (p < 0.05); however, AT inflammation and intestinal health markers were not improved to the same degree as HFàHFB (p < 0.05). Despite remaining on a HF obesogenic diet, introducing beans in established obesity improved the obese phenotype (intestinal health and adipose inflammation) more substantially than weight loss alone.


Asunto(s)
Dieta Alta en Grasa/métodos , Dieta Reductora/métodos , Suplementos Dietéticos , Obesidad/dietoterapia , Phaseolus , Tejido Adiposo/metabolismo , Animales , Biomarcadores/metabolismo , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Heces/microbiología , Microbioma Gastrointestinal , Inflamación , Mucosa Intestinal/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , Fenotipo , Polvos , Índice de Severidad de la Enfermedad
6.
J Nutr Biochem ; 72: 108216, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31476608

RESUMEN

Impaired intestinal health characterized by a dysbiotic microbial community and a dysfunctional epithelial barrier contributes to host inflammation and metabolic dysfunction in obesity. Fish oil (FO)-derived n-3 polyunsaturated fatty acids have been shown to improve aspects of the obese phenotype; however, their effect on obese intestinal health is unknown. This study aimed to determine the effect of dietary FO on the intestinal microenvironment, including the microbial community and epithelial barrier, in a mouse model of high-fat diet induced obesity and metabolic dysfunction. Male C57BL/6 mice were fed (12 weeks) either a high-fat diet (HF, 60% fat as kcal) or an isocaloric HF supplemented with Menhaden FO (5.3% kcal, HF + FO). 16S rRNA sequencing was used to determine changes in fecal microbiota. Intestinal (ileum and colon) and epididymal adipose tissue RNA was used to assess biomarkers of barrier integrity and inflammatory status, respectively. Serum was used to assess adipokine concentrations and insulin resistance. HF + FO diet altered the fecal microbiota by decreasing the abundance of Firmicutes and increasing the abundance of members of the Bacteroidetes phyla, as well as increasing the abundance of antiobesogenic Akkermansia muciniphila, compared to HF. Intestinal epithelial barrier functions were improved by HF + FO evidenced by increased mRNA expression of tight junction components, antimicrobial defenses and mucus barrier components. HF + FO-fed mice exhibited improvements in homeostatic model assessment of insulin resistance, oral glucose tolerance and serum adipokine concentrations and epididymal mRNA expression (increased adiponectin and decreased leptin) versus HF. HF + FO improved obese intestinal health and attenuated metabolic dysfunction associated with obesity.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Aceites de Pescado/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Obesidad/dietoterapia , Adipoquinas/sangre , Animales , Peso Corporal/efectos de los fármacos , Colon/efectos de los fármacos , Colon/fisiología , Suplementos Dietéticos , Ingestión de Alimentos/efectos de los fármacos , Ácidos Grasos Omega-3/metabolismo , Heces/microbiología , Microbioma Gastrointestinal/genética , Prueba de Tolerancia a la Glucosa , Íleon/efectos de los fármacos , Íleon/fisiología , Intestinos/fisiología , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/patología , Masculino , Ratones Endogámicos C57BL , Obesidad/etiología , Paniculitis/etiología , Paniculitis/prevención & control
7.
Nutrients ; 11(8)2019 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-31405019

RESUMEN

Dietary pulses, including lentils, are protein-rich plant foods that are enriched in intestinal health-promoting bioactives, such as non-digestible carbohydrates and phenolic compounds. The aim of this study was to investigate the effect of diets supplemented with cooked red lentils on the colonic microenvironment (microbiota composition and activity and epithelial barrier integrity and function). C57Bl/6 male mice were fed one of five diets: a control basal diet (BD), a BD-supplemented diet with 5, 10 or 20% cooked red lentils (by weight), or a BD-supplemented diet with 0.7% pectin (equivalent soluble fiber level as found in the 20% lentil diet). Red lentil supplementation resulted in increased: (1) fecal microbiota α-diversity; (2) abundance of short-chain fatty acid (SCFA)-producing bacteria (e.g., Prevotella, Roseburia and Dorea spp.); (3) concentrations of fecal SCFAs; (4) mRNA expression of SCFA receptors (G-protein-coupled receptors (GPR 41 and 43) and tight/adherens junction proteins (Zona Occulden-1 (ZO-1), Claudin-2, E-cadherin). Overall, 20% lentil had the greatest impact on colon health outcomes, which were in part explained by a change in the soluble and insoluble fiber profile of the diet. These results support recent public health recommendations to increase consumption of plant-based protein foods for improved health, in particular intestinal health.


Asunto(s)
Bacterias/metabolismo , Colon/microbiología , Culinaria , Fibras de la Dieta/metabolismo , Microbioma Gastrointestinal , Lens (Planta)/metabolismo , Semillas/metabolismo , Animales , Bacterias/genética , Cadherinas/genética , Cadherinas/metabolismo , Colon/metabolismo , Dieta , Fibras de la Dieta/administración & dosificación , Ácidos Grasos/metabolismo , Heces/microbiología , Calor , Masculino , Ratones Endogámicos C57BL , Mucinas/genética , Mucinas/metabolismo , Valor Nutritivo , Permeabilidad , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Uniones Estrechas/genética , Proteínas de Uniones Estrechas/metabolismo
8.
J Nutr Biochem ; 70: 91-104, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31195365

RESUMEN

Obesity is associated with impaired intestinal epithelial barrier function and an altered microbiota community structure, which contribute to host systemic inflammation and metabolic dysfunction. Fiber-rich common beans (Phaseolus vulgaris) promote intestinal health (microbiota and host epithelial barrier integrity) in lean mice. The objective was to assess the intestinal health promoting effects of navy bean supplementation during high-fat (HF)diet-induced obesity. Male C57BL/6 mice were fed either a high-fat (HF) diet (60% of kcal from fat) or an isocaloric HF diet supplemented with 15.7% (by weight) cooked navy bean powder (HF+B) for 12 weeks. Compared to HF, the HF+B diet altered the fecal microbiota community structure (16S rRNA gene sequencing), most notably increasing abundance of Akkermansia muciniphila (+19-fold), whose abundance typically decreases in obese humans and rodents. Additionally, HF+B fecal abundance of carbohydrate fermenting, short chain fatty acid (SCFA) producing Prevotella (+332-fold) and S24-7 (+1.6-fold) and fecal SCFA levels were increased. HF+B improved intestinal health and epithelial barrier integrity versus HF, evidenced by reduced serum fluorescein isothiocyanate (FITC)-dextran concentration in an in vivo gut permeability test, and increased intestinal mRNA expression of tight junction components (ZO-1, occludin), anti-microbial defenses (Reg3γ, IgA, Defα5, Defß2) and mucins (Muc2). Additionally, HF+B improved the systemic obese phenotype via reduced serum HOMA-IR and leptin:adiponectin ratio, and locally via attenuation of epididymal adipose tissue crown-like structure formation, adipocyte size, and inflammatory transcription factor (NFκBp65 and STAT3) activation. Therefore, navy bean supplementation improved obese intestinal health (microbiota and epithelial barrier integrity) and attenuated the severity of the obese phenotype.


Asunto(s)
Dieta Alta en Grasa , Inflamación/fisiopatología , Mucosa Intestinal/fisiopatología , Phaseolus , Adipoquinas/metabolismo , Tejido Adiposo/metabolismo , Akkermansia , Alimentación Animal , Animales , Peso Corporal , Metabolismo de los Hidratos de Carbono , Fibras de la Dieta , Suplementos Dietéticos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Heces , Fermentación , Fluoresceína-5-Isotiocianato , Microbioma Gastrointestinal , Mucosa Intestinal/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Permeabilidad , Fenotipo , Prevotella , ARN Ribosómico 16S/metabolismo , Verrucomicrobia
9.
J Nutr Biochem ; 56: 215-223, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29631142

RESUMEN

The enriched levels of nondigestible fermentable carbohydrates and phenolic compounds found in common beans can exert immunomodulatory effects within the colon that improve gut health and mitigate the severity of colitis-associated inflammatory pathology. Prior to acute colitis onset, C57Bl/6 mice were prefed isocaloric 20% cooked navy bean (NB) or black bean (BB) diets for 3 weeks and switched to control basal diet (BD) 24 h prior to colitis induction via 5-day exposure to dextran sodium sulfate (2% w/v in drinking water)+3 days of fresh water. The severity of the acute colitis phenotype was attenuated by bean prefeeding, evidenced by reduced colon tissue inflammatory transcription factor activation (NFκB, STAT3) and inflammatory mediator levels in the colon (IL-1ß, IL-6, IL-18 and MCP-1) and serum (TNFα, IL-6, IL-1ß, MCP-1) versus BD (P≤.05). Additionally, biomarkers of enhanced wound repair responses were increased by bean prefeeding including colon tissue protein levels of IL-22, IL-27 and activated (i.e., GTP-bound) Cdc42 and Rac1 versus BD (P≤.05). mRNA expressions of genes involved in normal colonic epithelial function and the promotion of epithelial barrier integrity, defense and/or restitution and wound closure including MUC1, RELMß, IgA and REG3γ were all increased in NB and BB prefed mice versus BD (P≤.05). Collectively, bean supplementation prior to colitis induction (i.e., mimicking disease relapse) primes the colonic microenvironment to attenuate the severity of the colitis inflammatory phenotype and maintain aspects of epithelial barrier function.


Asunto(s)
Colitis/dietoterapia , Enfermedades del Colon/dietoterapia , Suplementos Dietéticos , Epitelio/metabolismo , Inflamación/dietoterapia , Phaseolus , Animales , Biomarcadores/metabolismo , Colitis/patología , Colon/patología , Enfermedades del Colon/patología , Citocinas/metabolismo , Sulfato de Dextran , Dieta , Modelos Animales de Enfermedad , Fermentación , Mucosa Intestinal/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fenotipo
10.
Nutrients ; 9(12)2017 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-29186929

RESUMEN

Obesity is a global health concern with rising prevalence that increases the risk of developing other chronic diseases. A causal link connecting overnutrition, the development of obesity and obesity-associated co-morbidities is visceral adipose tissue (AT) dysfunction, characterized by changes in the cellularity of various immune cell populations, altered production of inflammatory adipokines that sustain a chronic state of low-grade inflammation and, ultimately, dysregulated AT metabolic function. Therefore, dietary intervention strategies aimed to halt the progression of obese AT dysfunction through any of the aforementioned processes represent an important active area of research. In this connection, fish oil-derived dietary long-chain n-3 polyunsaturated fatty acids (PUFA) in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to attenuate obese AT dysfunction through multiple mechanisms, ultimately affecting AT immune cellularity and function, adipokine production, and metabolic signaling pathways, all of which will be discussed herein.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Ácidos Grasos Omega-3/farmacología , Inmunomodulación , Obesidad/tratamiento farmacológico , Adipoquinas/sangre , Tejido Adiposo/metabolismo , Adiposidad/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Humanos , Inmunidad Celular , Inflamación/sangre , Inflamación/tratamiento farmacológico , Obesidad/sangre , Transducción de Señal
11.
Mol Nutr Food Res ; 60(11): 2396-2412, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27349947

RESUMEN

SCOPE: This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. METHODS AND RESULTS: C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). CONCLUSION: These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis.


Asunto(s)
Colitis/inducido químicamente , Sulfato de Dextran/efectos adversos , Rutina/farmacología , Sulfatos/farmacología , Animales , Colon/metabolismo , Citocinas/metabolismo , Suplementos Dietéticos , Modelos Animales de Enfermedad , Inflamación , Interleucinas/metabolismo , Mucosa Intestinal/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Rutina/análisis , Interleucina-22
12.
J Nutr Biochem ; 32: 29-38, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27142734

RESUMEN

Typically fatty acids (FA) exert differential immunomodulatory effects with n-3 [α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and n-6 [linoleic acid (LA) and arachidonic acid (AA)] exerting anti- and pro-inflammatory effects, respectively. This over-simplified interpretation is confounded by a failure to account for conversion of the parent FA (LA and ALA) to longer-chain bioactive products (AA and EPA/DHA, respectively), thereby precluding discernment of the immunomodulatory potential of specific FA. Therefore, we utilized the Δ6-desaturase model, wherein knockout mice (D6KO) lack the Fads2 gene encoding for the rate-limiting enzyme that initiates FA metabolism, thereby providing a model to determine specific FA immunomodulatory effects. Wild-type (WT) and D6KO mice were fed one of four isocaloric diets differing in FA source (9weeks): corn oil (LA-enriched), arachidonic acid single cell oil (AA-enriched), flaxseed oil (ALA-enriched) or menhaden fish oil (EPA/DHA-enriched). Splenic mononuclear cell cytokine production in response to lipopolysaccharide (LPS), T-cell receptor (TCR) and anti-CD40 stimulation was determined. Following LPS stimulation, AA was more bioactive compared to LA, by increasing inflammatory cytokine production of IL-6 (1.2-fold) and TNFα (1.3-fold). Further, LPS-stimulated IFNγ production in LA-fed D6KO mice was reduced 5-fold compared to LA-fed WT mice, indicating that conversion of LA to AA was necessary for cytokine production. Conversely, ALA exerted an independent immunomodulatory effect from EPA/DHA and all n-3 FA increased LPS-stimulated IL-10 production versus LA and AA. These data definitively identify specific immunomodulatory effects of individual FA and challenge the simplified view of the immunomodulatory effects of n-3 and n-6 FA.


Asunto(s)
Suplementos Dietéticos , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Inmunomodulación , Leucocitos Mononucleares/inmunología , Bazo/inmunología , Animales , Células Cultivadas , Cruzamientos Genéticos , Citocinas/metabolismo , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/metabolismo , Femenino , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Noqueados , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo
13.
J Nutr Biochem ; 34: 61-72, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27208584

RESUMEN

Adipocyte-macrophage cross-talk propagates immune responses in obese adipose tissue (AT). Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) mitigate inflammation, partly through up-regulation of adiponectin; however, specific mechanisms are unclear. We determined if adipocyte-macrophage cross-talk could be mitigated by dietary LC n-3 PUFA and if this was dependent on adiponectin-mediated signaling. We utilized an in vitro co-culture model mimicking the ratio of adipocytes:macrophages in obese AT, whereby 3T3-L1 adipocytes were co-cultured with splenic CD11b(+) macrophages from C57BL/6 mice fed high-fat control (HF-CON; 34% w/w fat) or fish oil diets (HF-FO; 34% w/w fat containing 7.6% w/w FO), as well as mice fed low-fat control (LF-CON; 10% w/w fat) or FO diets (LF-FO; 10% w/w fat containing 3% w/w FO). Co-culture conditions tested effects of soluble mediator-driven mechanisms (trans-well system), cell contact and low-dose lipopolysaccharide (LPS) mimicking acute or chronic inflammatory conditions. HF-FO macrophages from acute LPS-stimulated trans-well co-cultures had decreased mRNA expression of Casp1, Il1ß and Il18, as well as cellular caspase-1 activity compared to HF-CON macrophages (P≤.05). Moreover, adipocytes from acute LPS-stimulated HF-FO co-cultures had decreased caspase-1 activity and decreased IL-1ß/IL-18 levels following chronic LPS pretreatment compared to HF-CON co-cultures (P≤.05). Additionally, in contact co-cultures with adiponectin-neutralizing antibody, the FO-mediated modulation of NFκB activity and decrease in phosphorylated p65 NFκB, expression of NLRP3 inflammasome genes, M1 macrophage marker genes and inflammatory cytokine/chemokine secretion were controlled partly through adiponectin, while cellular caspase-1 activity and IL-1ß/1L-18 levels were decreased independently of adiponectin (P≤.05). LC n-3 PUFA may decrease the intensity of adipocyte-macrophage cross-talk to mitigate obesity-associated pathologies.


Asunto(s)
Adipocitos Blancos/metabolismo , Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Inflamasomas/metabolismo , Macrófagos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Obesidad/dietoterapia , Células 3T3-L1 , Adipocitos Blancos/inmunología , Adipocitos Blancos/patología , Animales , Antiinflamatorios no Esteroideos/análisis , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Antígeno CD11b/metabolismo , Comunicación Celular , Células Cultivadas , Técnicas de Cocultivo , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos/análisis , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-3/metabolismo , Femenino , Aceites de Pescado/química , Aceites de Pescado/uso terapéutico , Regulación de la Expresión Génica , Inflamasomas/inmunología , Macrófagos/inmunología , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Obesidad/inmunología , Obesidad/metabolismo , Obesidad/patología , Bazo/inmunología , Bazo/metabolismo , Bazo/patología
14.
J Nutr Biochem ; 28: 129-39, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26878790

RESUMEN

Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmß and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmß, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1ß, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies.


Asunto(s)
Colitis/dietoterapia , Dieta , Inflamación/dietoterapia , Microbiota , Phaseolus , Animales , Heces/microbiología , Mediadores de Inflamación/metabolismo , Factor 4 Similar a Kruppel , Ratones , Ratones Endogámicos C57BL , Filogenia , ARN Mensajero/genética
15.
Mol Nutr Food Res ; 60(3): 621-30, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26616354

RESUMEN

SCOPE: CD8(+) T cell/adipocyte paracrine interactions represent a critical step in the development of the obese inflammatory phenotype that is disrupted by long-chain n-3 PUFA. Our objective was to determine the effect of flaxseed-derived n-3 PUFA (α-linolenic acid) on these paracrine interactions. METHODS AND RESULTS: C57BL/6 mice were fed 3.5% flaxseed oil (FX) + 3.5% corn oil diet w/w or an isocaloric 7% corn oil w/w control diet (CON) for 3 wk. 3T3-L1 adipocytes and purified primary splenic CD8(+) T cells were cocultured at an obese cellular ratio (10% CD8(+) T cells) and LPS-stimulated (10 ng/mL mimicking obese circulating endotoxin levels) for 24 h. FX cocultures reduced (i) secreted IL-6, tumor necrosis factor α (TNF-α), macrophage chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α), and RANTES (regulated on activation, normal T cell expressed and secreted) levels; (ii) activation of inflammatory transcription factors NFκB (nuclear factor kappa-light-chain-enhancer of activated B cell) p65 and signal transducer and activator of transcription-3 (STAT3); and (iii) RAW264.7 macrophage chemotaxis versus CON (p ≤ 0.05). Coculture of pre-inflamed adipocytes (10 ng/mL LPS, 24 h prior to CD8(+) T-cell addition) resulted in reduced secretion of IL-6, IL-1ß, MCP-1, MCP-3, MIP-1ß, and RANTES in FX cocultures versus CON (p ≤ 0.05). CONCLUSION: FX exerts an anti-chemotactic and anti-inflammatory effect on CD8(+) T cell/adipocyte paracrine interactions (cross-talk), which has the potential to mitigate macrophage chemotaxis which drives components of the obese phenotype.


Asunto(s)
Adipocitos/efectos de los fármacos , Antiinflamatorios no Esteroideos/farmacología , Linfocitos T CD8-positivos/efectos de los fármacos , Quimiotaxis/efectos de los fármacos , Aceite de Linaza/farmacología , Adipocitos/metabolismo , Animales , Linfocitos T CD8-positivos/metabolismo , Comunicación Celular/efectos de los fármacos , Técnicas de Cocultivo , Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos/metabolismo , Ácidos Grasos Omega-3/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Ratones Endogámicos C57BL
16.
J Nutr ; 145(4): 829-38, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25833786

RESUMEN

BACKGROUND: Obese adipose tissue (AT) inflammation is characterized by dysregulated adipokine production and immune cell accumulation. Cluster of differentiation (CD) 8+ T cell AT infiltration represents a critical step that precedes macrophage infiltration. n-3 (ω-3) Polyunsaturated fatty acids (PUFAs) exert anti-inflammatory effects in obese AT, thereby disrupting AT inflammatory paracrine signaling. OBJECTIVE: We assessed the effect of n-3 PUFAs on paracrine interactions between adipocytes and primary CD8+ T cells co-cultured at the cellular ratio observed in obese AT. METHODS: C57BL/6 mice were fed either a 3% menhaden fish-oil + 7% safflower oil (FO) diet (wt:wt) or an isocaloric 10% safflower oil (wt:wt) control (CON) for 3 wk, and splenic CD8+ T cells were isolated by positive selection (via magnetic microbeads) and co-cultured with 3T3-L1 adipocytes. Co-cultures were unstimulated (cells alone), T cell receptor stimulated, or lipopolysaccharide (LPS) stimulated for 24 h. RESULTS: In LPS-stimulated co-cultures, FO reduced secreted protein concentrations of interleukin (IL)-6 (-42.6%), tumor necrosis factor α (-67%), macrophage inflammatory protein (MIP) 1α (-52%), MIP-1ß (-62%), monocyte chemotactic protein (MCP) 1 (-23%), and MCP-3 (-19%) vs. CON, which coincided with a 74% reduction in macrophage chemotaxis toward secreted chemotaxins in LPS-stimulated FO-enriched co-culture-conditioned media. FO increased mRNA expression of the inflammatory signaling negative regulators monocyte chemoattractant 1-induced protein (Mcpip; +9.3-fold) and suppressor of cytokine signaling 3 (Socs3; +1.7-fold), whereas FO reduced activation of inflammatory transcription factors nuclear transcription factor κB (NF-κB) p65 and signal transducer and activator of transcription 3 (STAT3) by 27% and 33%, respectively. Finally, mRNA expression of the inflammasome components Caspase1 (-36.4%), Nod-like receptor family pyrin domain containing 3 (Nlrp3; -99%), and Il1b (-68.8%) were decreased by FO compared with CON (P ≤ 0.05). CONCLUSION: FO exerted an anti-inflammatory and antichemotactic effect on the cross-talk between CD8+ T cells and adipocytes and has implications in mitigating macrophage-centered AT-driven components of the obese phenotype.


Asunto(s)
Adipoquinas/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado/administración & dosificación , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular/efectos de los fármacos , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiocina CCL3/genética , Quimiocina CCL3/metabolismo , Quimiocina CCL4/genética , Quimiocina CCL4/metabolismo , Quimiocina CCL7/genética , Quimiocina CCL7/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Factor de Transcripción ReIA/genética , Factor de Transcripción ReIA/metabolismo
17.
Nutrients ; 6(11): 4760-93, 2014 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-25360510

RESUMEN

Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Ácidos Grasos Omega-3/administración & dosificación , Obesidad/tratamiento farmacológico , Obesidad/epidemiología , Comunicación Paracrina/efectos de los fármacos , Adiponectina/metabolismo , Aromatasa/metabolismo , Neoplasias de la Mama/complicaciones , Citocinas/metabolismo , Estrógenos/metabolismo , Ácidos Grasos Omega-6/administración & dosificación , Femenino , Humanos , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Leptina/metabolismo , Obesidad/complicaciones , Prevalencia
18.
Am J Physiol Gastrointest Liver Physiol ; 306(12): G1042-55, 2014 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-24763556

RESUMEN

Flaxseed (FS), a dietary oilseed, contains a variety of anti-inflammatory bioactives, including fermentable fiber, phenolic compounds (lignans), and the n-3 polyunsaturated fatty acid (PUFA) α-linolenic acid. The objective of this study was to determine the effects of FS and its n-3 PUFA-rich kernel or lignan- and soluble fiber-rich hull on colitis severity in a mouse model of acute colonic inflammation. C57BL/6 male mice were fed a basal diet (negative control) or a basal diet supplemented with 10% FS, 6% kernel, or 4% hull for 3 wk prior to and during colitis induction via 5 days of 2% (wt/vol) dextran sodium sulfate (DSS) in their drinking water (n = 12/group). An increase in anti-inflammatory metabolites (hepatic n-3 PUFAs, serum mammalian lignans, and cecal short-chain fatty acids) was associated with consumption of all FS-based diets, but not with anti-inflammatory effects in DSS-exposed mice. Dietary FS exacerbated DSS-induced acute colitis, as indicated by a heightened disease activity index and an increase in colonic injury and inflammatory biomarkers [histological damage, apoptosis, myeloperoxidase, inflammatory cytokines (IL-6 and IL-1ß), and NF-κB signaling-related genes (Nfkb1, Ccl5, Bcl2a1a, Egfr, Relb, Birc3, and Atf1)]. Additionally, the adverse effect of the FS diet was extended systemically, as serum cytokines (IL-6, IFNγ, and IL-1ß) and hepatic cholesterol levels were increased. The adverse effects of FS were not associated with alterations in fecal microbial load or systemic bacterial translocation (endotoxemia). Collectively, this study demonstrates that although consumption of a 10% FS diet enhanced the levels of n-3 PUFAs, short-chain polyunsaturated fatty acids, and lignans in mice, it exacerbated DSS-induced colonic injury and inflammation.


Asunto(s)
Colitis/metabolismo , Colon/lesiones , Lino/toxicidad , Mucosa Intestinal/metabolismo , Enfermedad Aguda , Animales , Colitis/inducido químicamente , Colitis/patología , Colon/metabolismo , Colon/patología , Sulfato de Dextran , Suplementos Dietéticos/toxicidad , Modelos Animales de Enfermedad , Ácidos Grasos Omega-3/metabolismo , Mucosa Intestinal/patología , Masculino , Ratones , Ratones Endogámicos C57BL
19.
Cell Mol Life Sci ; 66(24): 3873-94, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19669093

RESUMEN

Together with the estrogen receptor (ER) alpha, estrogen receptor beta (ER beta ) mediates many of the physiological effects of estrogens. As ER beta is crucially involved in a variety of important physiological processes, its activity should be tightly regulated. ER beta regulation is achieved by hormone binding as well as by posttranslational modifications of the receptor. Furthermore, ER beta expression levels are under circadian control and can be regulated by DNA methylation of the ER beta promoter region. There are also a number of factors that can interfere with ER beta activity, such as phytoestrogens, endocrine disruptive chemicals, and growth factors. In this article, we outline different mechanisms of ER beta regulation and how they are implicated in various diseases. We also discuss how these insights might help to specifically target ER beta in drug design.


Asunto(s)
Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Neoplasias/patología , Empalme Alternativo , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Humanos , Modelos Biológicos , Neoplasias/genética , Neoplasias/metabolismo , Fitoestrógenos/metabolismo , Unión Proteica , Procesamiento Proteico-Postraduccional
20.
J Steroid Biochem Mol Biol ; 112(1-3): 13-9, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18703142

RESUMEN

Previously we have shown that MCF-7 human breast tumor growth is stimulated after prolonged treatment with dietary soy protein isolate (SPI). However, the effects are attenuated when SPI is combined with flaxseed (FS). This study determined the changes that occur in tumor growth biomarkers, after both short- and long-term treatment with SPI, FS or their combination, to help identify signaling pathways potentially involved in SPI-stimulated tumor growth. Ovariectomized mice with established MCF-7 tumors were fed basal diet (control), 20%SPI, 10%FS, or SPI+FS for 2 or 25 weeks. After 2 weeks, there were no differences in tumor size, however, compared with control, SPI-treated tumors had higher IGF-IR and cyclin D1 while FS and SPI+FS-fed mice had lower pMAPK expression. After 25 weeks, SPI-treated tumors were larger, had higher proliferation, ERalpha, cyclin D1, IGF-IR, and pMAPK and lower ERbeta and HER2 levels. When combined with FS, however, the effects on these tumor biomarkers induced by SPI were attenuated. This study demonstrates that SPI and FS differently modulate tumor biomarkers of estrogen and growth factor signaling pathways, after both short- and long-term treatment, which may indicate a role of these pathways in the tumor stimulatory effects of SPI and the tumor inhibitory effects of FS.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Lino/química , Péptidos y Proteínas de Señalización Intercelular/fisiología , Neoplasias Experimentales/metabolismo , Preparaciones de Plantas/farmacología , Receptores de Estrógenos/metabolismo , Proteínas de Soja/efectos adversos , Animales , Línea Celular Tumoral , Proliferación Celular , Ciclina D1/metabolismo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/patología , Ovariectomía , Preparaciones de Plantas/efectos adversos , Receptor IGF Tipo 1/metabolismo , Transducción de Señal , Proteínas de Soja/administración & dosificación , Trasplante Heterólogo
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