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1.
Methods Mol Biol ; 2769: 57-65, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38315388

RESUMO

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD). Obesity is a known risk factor of NASH, which, in turn, increases the risk of developing cirrhosis (liver scarring) and hepatocellular carcinoma (HCC). In addition to being a potentially life-threatening condition, public health concerns surrounding NASH are amplified by the lack of FDA-approved treatments. Although various preclinical models reflecting both the histopathology and the pathophysiological progression of human NASH exist, most of these models are diet-based and require 6-13 months for NASH symptom manifestation. Here, we describe a simple and rapid-progression model of NASH and NASH-driven HCC in mice. Mice received a western diet equivalent (WD; i.e., a high-fat, high-fructose, and high-cholesterol diet), high-sugar water (23.1 g/L fructose and 18.9 g/L glucose), and weekly intraperitoneal injections of carbon tetrachloride (CCl4) at a dose of 0.2 µL/g of body weight. The resulting phenotype, consisting in liver fibrosis and HCC, appeared within 24 weeks of diet/treatment initiation and presented similar histological and transcriptomic features as human NASH and NASH-driven HCC, thereby supporting the adequacy of this preclinical model for the development and evaluation of drugs that can prevent or reverse these diseases.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Carcinoma Hepatocelular/genética , Tetracloreto de Carbono/toxicidade , Neoplasias Hepáticas/patologia , Dieta Ocidental/efeitos adversos , Modelos Animais de Doenças , Cirrose Hepática/patologia , Frutose , Dieta Hiperlipídica/efeitos adversos , Fígado/patologia , Camundongos Endogâmicos C57BL
2.
Sci Rep ; 14(1): 4025, 2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38369624

RESUMO

Prolonged use of antibacterial mouthwash is linked to an increased risk of systemic disease. We aimed to investigate if disturbing the oral microbiota would impact the lower gut microbiome with functional effects in diet-induced obesity. Mice were exposed to oral chlorhexidine and fed a Western diet (WD). Food intake and weight gain were monitored, and metabolic function, blood pressure, and microbiota were analyzed. Chlorhexidine reduced the number of viable bacteria in the mouth and lowered species richness in the gut but with proportional enrichment of some bacteria linked to metabolic pathways. In mice fed a Western diet, chlorhexidine reduced weight gain, body fat, steatosis, and plasma insulin without changing caloric intake, while increasing colon triglycerides and proteins, suggesting reduced absorption of these nutrients. The mechanisms behind these effects as well as the link between the oral microbiome and small intestinal function need to be pinpointed. While the short-term effects of chlorhexidine in this model appear beneficial, potential long-term disruptions in the oral and gut microbiota and possible malabsorption should be considered.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Antissépticos Bucais/farmacologia , Dieta Ocidental/efeitos adversos , Clorexidina/farmacologia , Dieta Hiperlipídica/efeitos adversos , Aumento de Peso , Tecido Adiposo , Nutrientes , Camundongos Endogâmicos C57BL
3.
J Biochem Mol Toxicol ; 38(2): e23644, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348714

RESUMO

The nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced by WD-rich sugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label-free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up- and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR-treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.


Assuntos
Carnosina , Hepatopatia Gordurosa não Alcoólica , Humanos , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Carnosina/farmacologia , Carnosina/uso terapêutico , Dieta Ocidental/efeitos adversos , Proteômica/métodos , Fígado/metabolismo , Modelos Animais , Dieta Hiperlipídica , Metabolismo dos Lipídeos , Modelos Animais de Doenças
4.
Food Funct ; 15(3): 1250-1264, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38194248

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. NAFLD is caused by numerous factors, including the genetic susceptibility, oxidative stress, unhealthy diet, and gut microbiota dysbiosis. Among these, gut microbiota is a key factor and plays an important role in the development of NAFLD. Therefore, modulating the composition and structure of gut microbiota might provide a new intervention strategy for NAFLD. Highland barley ß-glucan (HBG) is a polysaccharide that can interact with gut microbiota after entering the lower gastrointestinal tract and subsequently improves NAFLD. Therefore, a Western diet was used to induce NAFLD in mouse models and the intervention effects and underlying molecular mechanisms of HBG on NAFLD mice based on gut microbiota were explored. The results indicated that HBG could regulate the composition of gut microbiota in NAFLD mice. In particular, HBG increased the abundance of short-chain fatty acids (SCFA)-producing bacteria (Prevotella-9, Bacteroides, and Roseburia) as well as SCFA contents. The increase in SCFA contents might activate the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, thereby improving the liver lipid metabolism disorder and reducing liver lipid deposition.


Assuntos
Microbioma Gastrointestinal , Hordeum , Hepatopatia Gordurosa não Alcoólica , beta-Glucanas , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , beta-Glucanas/farmacologia , Dieta Ocidental/efeitos adversos , Fígado/metabolismo , Suplementos Nutricionais , Lipídeos/farmacologia , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica
5.
Maturitas ; 179: 107868, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37925868

RESUMO

OBJECTIVE: To explore the association between three previously identified and validated dietary patterns (Western, Prudent and Mediterranean) and breast cancer risk by tumour subtype and menopausal status. METHODS: Data from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided epidemiological information (including diet and cancer incidence) from 24,892 women (639 breast cancer cases) recruited between 1992 and 1996. The associations between adherence to the three dietary patterns and breast cancer risk (overall and by tumour subtype) were explored by fitting multivariate Cox proportional hazards regression models stratified by region, among other variables. A possible interaction with menopausal status (changing over time) was explored. RESULTS: No clear association of the Prudent and Mediterranean dietary patterns with breast cancer risk was found. When compared with women with a level of adherence to the Western diet in the first quartile, women with a level of adherence in the third (hazard ratio (95 % confidence interval) (HR(95%CI)):1.37 (1.07;1.77)) and fourth quartiles (1.37 (1.03;1.83)); p for curvature of splines = 0.016) showed a non-linear increased risk, especially postmenopausal women (HR (95 % CI) 1.30 (0.98;1.72) in the third and 1.42 (1.04;1.94) in the fourth quartiles; p for curvature of splines = 0.081) and for estrogen or progesterone receptor positive with human epidermal growth factor receptor 2 negative tumours (HR (95 % CI) 1.62 (1.10;2.38) and 1.71 (1.11;2.63) for the third and fourth quartiles respectively; p for curvature of splines = 0.013). CONCLUSIONS: Intake of foods such as high-fat dairy products, red and processed meats, refined grains, sweets, caloric drinks, convenience food and sauces might be associated with a higher risk of breast cancer.


Assuntos
Neoplasias da Mama , Dieta Ocidental , Humanos , Feminino , Dieta Ocidental/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Espanha/epidemiologia , Fatores de Risco , Estudos Prospectivos , Dieta/efeitos adversos , Carne , Modelos de Riscos Proporcionais
6.
BMC Biol ; 21(1): 243, 2023 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-37926812

RESUMO

BACKGROUND: Accumulating evidence supports that the Western diet (WD), a diet high in saturated fat and sugary drinks, contributes to the pathogenesis of anxiety disorders, which are the most prevalent mental disorders worldwide. However, the underlying mechanisms by which WD causes anxiety remain unclear. Abundant expression of taste receptor type 1 member 3 (TAS1R3) has been identified in the hypothalamus, a key brain area involved in sensing peripheral nutritional signals and regulating anxiety. Thus, we investigated the influence of excessive WD intake on anxiety and mechanisms by which WD intake affects anxiety development using wild-type (WT) and Tas1r3 deficient (Tas1r3-/-) mice fed a normal diet (ND) or WD for 12 weeks. RESULTS: WD increased anxiety in male WT mice, whereas male Tas1r3-/- mice were protected from WD-induced anxiety, as assessed by open field (OF), elevated plus maze (EPM), light-dark box (LDB), and novelty-suppressed feeding (NSF) tests. Analyzing the hypothalamic transcriptome of WD-fed WT and Tas1r3-/- mice, we found 1,432 genes significantly up- or down-regulated as a result of Tas1r3 deficiency. Furthermore, bioinformatic analysis revealed that the CREB/BDNF signaling-mediated maintenance of neuronal regeneration, which can prevent anxiety development, was enhanced in WD-fed Tas1r3-/- mice compared with WD-fed WT mice. Additionally, in vitro studies further confirmed that Tas1r3 knockdown prevents the suppression of Creb1 and of CREB-mediated BDNF expression caused by high levels of glucose, fructose, and palmitic acid in hypothalamic neuronal cells. CONCLUSIONS: Our results imply that TAS1R3 may play a key role in WD-induced alterations in hypothalamic functions, and that inhibition of TAS1R3 overactivation in the hypothalamus could offer therapeutic targets to alleviate the effects of WD on anxiety.


Assuntos
Ansiedade , Dieta Ocidental , Receptores Acoplados a Proteínas G , Animais , Masculino , Camundongos , Ansiedade/genética , Fator Neurotrófico Derivado do Encéfalo , Dieta Ocidental/efeitos adversos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G/genética
7.
Life Sci ; 335: 122259, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37949212

RESUMO

AIMS: To determine if cellulose nanofibrils (CNF) have potential applications as food additives. MATERIALS AND METHODS: Male C57BL/6 mice on a Western diet were exposed to CNF for one month at a dose of 30 mg/kg by gavage. Male NOD mice, a model for type 1 diabetes (T1D), were used in a six-month study. KEY FINDINGS: Sequencing analysis of 16S rRNA genes suggested significant changes in gut microbiome of male C57BL/6 mice exposed to CNF. Analysis of functional metagenomics indicated that many of the functional contents that might be altered following CNF ingestion were associated with lipid and carbohydrate processing. Further studies in NOD mice suggested that there were some decreases in the blood glucose levels during the insulin tolerance test and glucose tolerance test following CNF treatment. However, these small decreases were not considered biologically meaningful as there were no significant changes in either the area under the curve or the first-order rate constant for glucose disappearance. Moreover, serum concentrations of cytokines/chemokines including IL-3, IL-12(p70) and the keratinocyte chemoattractant were increased following chronic exposure to CNF. In addition, behavioral studies suggested that the percentage of immobility time during the tail-suspension test was significantly increased following six months of exposure to CNF in NOD mice, signifying an increase in depression-related behavior. SIGNIFICANCE: Collectively, long-term CNF consumption was associated with changes in the ecology of the gut microbiome, immune homeostasis, and possibly energy metabolism and mental health in male NOD mice on a Western diet.


Assuntos
Microbioma Gastrointestinal , Masculino , Animais , Camundongos , Camundongos Endogâmicos NOD , Dieta Ocidental/efeitos adversos , RNA Ribossômico 16S/genética , Depressão , Camundongos Endogâmicos C57BL
8.
Gut Microbes ; 15(2): 2283147, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37990909

RESUMO

Host diet and gut microbiota interact to contribute to perioperative complications, including anastomotic leak (AL). Using a murine surgical model of colonic anastomosis, we investigated how diet and fecal microbial transplantation (FMT) impacted the intestinal microbiota and if a predictive signature for AL could be determined. We hypothesized that a Western diet (WD) would impact gut microbial composition and that the resulting dysbiosis would correlate with increased rates of AL, while FMT from healthy, lean diet (LD) donors would reduce the risk of AL. Furthermore, we predicted that surgical outcomes would allow for the development of a microbial preclinical translational tool to identify AL. Here, we show that AL is associated with a dysbiotic microbial community characterized by increased levels of Bacteroides and Akkermansia. We identified several key taxa that were associated with leak formation, and developed an index based on the ratio of bacteria associated with the absence and presence of leak. We also highlight a modifiable connection between diet, microbiota, and anastomotic healing, potentially paving the way for perioperative modulation by microbiota-targeted therapeutics to reduce AL.


Assuntos
Microbioma Gastrointestinal , Camundongos , Humanos , Animais , Modelos Animais de Doenças , Colo/cirurgia , Colo/microbiologia , Anastomose Cirúrgica/efeitos adversos , Transplante de Microbiota Fecal/métodos , Fístula Anastomótica/microbiologia , Dieta Ocidental/efeitos adversos
9.
Ecotoxicol Environ Saf ; 268: 115688, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37992649

RESUMO

Nonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver steatosis, hypertrophy/inflammation of adipose tissue and deregulation of gut microbiome. Glyphosate and 2,4-D are some of the most applied herbicides worldwide, and their roles in NAFLD have not been investigated. Thus, the present study evaluated whether glyphosate and 2,4-D, in single or mixed exposure, alter WD-induced NAFLD in a mouse model. Male C57Bl/6 mice (n = 10/group) received a fat (30% lard, 0.02% cholesterol), and sucrose-rich diet (20%) and high sugar solution (23.1 and 18.9 g/L of fructose and glucose) for 6 months. Simultaneously, animals received glyphosate (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or their combination (0.05 +0.02 or 5 +2 mg/kg/day) by intragastrical administration (5 ×/week). Doses were based on the Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) levels. Herbicide exposures featured differential responses. WD-induced obesity, hypercholesterolemia, and hyperglycemia remained unaltered. Compared to the group receiving only WD, only the concomitant exposure to WD and 2,4-D (2 mg) enhanced the percentage of mice with moderate/severe hepatic inflammation, CD68 macrophage infiltration, and malondialdehyde levels in the liver. In line, this herbicide modulated immune response- (including Cd4, C8b, Cd28, Cxcr3, Cxcr6) and oxidative stress-related (such as Gsta1, Gsta2, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Nqo1, Gpx2) genes in the hepatic transcriptome analysis. This exposure also enriched pro-inflammatory Deferribacteres phylum in fecal microbiome. In general, the herbicide mixtures did not feature the same effects attributed to 2,4-D isolated exposure. Our findings indicate that 2,4-D, at a dose within the toxicological limits, was able to induce disturbances in mainly at the liver and gut axes involved in NAFLD development in male mice.


Assuntos
Herbicidas , Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Fígado , Inflamação , Tecido Adiposo , Dieta Ocidental/efeitos adversos , Herbicidas/toxicidade , Ácido 2,4-Diclorofenoxiacético/toxicidade , Camundongos Endogâmicos C57BL
10.
PLoS One ; 18(10): e0292432, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37819925

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global health problem. Identification of factors contributing to the onset and progression of NAFLD have the potential to direct novel strategies to combat NAFLD. METHODS: We examined the time course of western diet (WD)-induced NAFLD and its progression to nonalcoholic steatohepatitis (NASH) in age-matched female and male Ldlr-/- mice, with time-points at 1, 4, 8, 20 and 40 weeks on the WD. Controls included Ldlr-/- mice maintained on a purified low-fat diet (LFD) for 1 and 40 weeks. The approach included quantitation of anthropometric, plasma and liver markers of disease, plus hepatic histology, lipids, oxylipins, gene expression and selected metabolites. RESULTS: One week of feeding the WD caused a significant reduction in hepatic essential fatty acids (EFAs: 18:2, ω6, 18:3, ω3) which preceded the decline in many C20-22 ω3 and ω6 polyunsaturated fatty acids (PUFA) and PUFA-derived oxylipins after 4 weeks on the WD. In addition, expression of hepatic inflammation markers (CD40, CD44, Mcp1, Nlrp3, TLR2, TLR4, Trem2) increased significantly in both female & male mice after one week on the WD. These markers continued to increase over the 40-week WD feeding study. WD effects on hepatic EFA and inflammation preceded all significant WD-induced changes in body weight, insulin resistance (HOMA-IR), oxidative stress status (GSH/GSSG ratio) and histological and gene expression markers of macrosteatosis, extracellular matrix remodeling and fibrosis. CONCLUSIONS: Our findings establish that feeding Ldlr-/- mice the WD rapidly lowered hepatic EFAs and induced key inflammatory markers linked to NASH. Since EFAs have an established role in inflammation and hepatic inflammation plays a major role in NASH, we suggest that early clinical assessment of EFA status and correcting EFA deficiencies may be useful in reducing NASH severity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Feminino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Ocidental/efeitos adversos , Oxilipinas/metabolismo , Fígado/metabolismo , Inflamação/metabolismo , Ácidos Graxos Insaturados/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo
11.
Food Res Int ; 173(Pt 2): 113450, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803779

RESUMO

In this study, we aimed to evaluate the impact of consuming refined mackerel oil (MO) from rest raw material on hepatic fat accumulation, glucose tolerance, and metabolomic changes in the liver from male C57BL/6N mice. The mice were fed either a Western diet (WD) or a chow diet, with 30 g or 60 g MO per kg of diet (3% or 6%) for 13 weeks. Body weight, energy intake, and feed efficiency were monitored throughout the experiment. A glucose tolerance test was conducted after 11 weeks, and metabolomic analyses of the liver were performed at termination. Inclusion of MO in the WD, but not in the chow diet, led to increased liver weight, hepatic lipid accumulation, elevated fasting blood glucose, reduced glucose tolerance, and insulin sensitivity. Hepatic levels of eicosapentaenoic and docosahexaenoic acid increased, but no changes in levels of saturated and monounsaturated fatty acids were observed. The liver metabolomic profile was different between mice fed a WD with or without MO, with a reduction in choline ether lipids, phosphatidylcholines, and sphingomyelins in mice fed MO. This study demonstrates that supplementing the WD, but not the chow diet, with refined MO accelerates accumulation of hepatic fat droplets and negatively affects blood glucose regulation. The detrimental effects of supplementing a WD with MO were accompanied by increased fat digestibility and overall energy intake, and lower levels of choline and choline-containing metabolites in liver tissue.


Assuntos
Dieta Ocidental , Perciformes , Camundongos , Masculino , Animais , Dieta Ocidental/efeitos adversos , Glicemia/metabolismo , Colina/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Ácidos Graxos Monoinsaturados
12.
Sci Rep ; 13(1): 16832, 2023 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803087

RESUMO

Dietary saturate fatty acids (SFAs) have been consistently linked to atherosclerosis and obesity, both of which are characterized by chronic inflammation and impaired lipid metabolism. In comparison, the effects of linoleic acid (LA), the predominant polyunsaturated fatty acid in the Western diet, seem to diverge. Data from human studies suggest a positive association between high dietary intake of LA and the improvement of cardiovascular risk. However, excessive LA intake has been implicated in the development of obesity. Concerns have also been raised on the potential pro-inflammatory properties of LA metabolites. Herein, by utilizing a mouse model with liver-specific Ldlr knockdown, we directly determined the effects of replacing SFAs with LA in a Western diet on the development of obesity and atherosclerosis. Specifically, mice treated with a Ldlr ASO were placed on a Western diet containing either SFA-rich butter (WD-B) or LA-rich corn oil (WD-CO) for 12 weeks. Despite of showing no changes in body weight gain or adiposity, mice on WD-CO exhibited significantly less atherosclerotic lesions compared to those on WD-B diet. Reduced lesion formation in the WD-CO-fed mice corresponded with a reduction of plasma triglyceride and cholesterol content, especially in VLDL and LDL, and ApoB protein levels. Although it increased expression of proinflammatory cytokines TNF-α and IL-6 in the liver, WD-CO did not appear to affect hepatic injury or damage when compared to WD-B. Collectively, our results indicate that replacing SFAs with LA in a Western diet could reduce the development of atherosclerosis independently of obesity.


Assuntos
Aterosclerose , Ácidos Graxos , Camundongos , Humanos , Animais , Ácidos Graxos/metabolismo , Ácido Linoleico/metabolismo , Dieta Ocidental/efeitos adversos , Fígado/metabolismo , Aterosclerose/patologia , Receptores de LDL/genética , Receptores de LDL/metabolismo , Obesidade/metabolismo
13.
Cells ; 12(18)2023 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-37759553

RESUMO

Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disease in Western countries. It is becoming increasingly evident that peripheral organ-centered inflammatory diseases, including liver diseases, are linked with brain dysfunctions. Therefore, this study aims to unravel the effect of MASLD on brain histology, cognitive functions, and neurotransmitters. For this purpose, mice fed for 48 weeks on standard (SD) or Western diet (WD) were evaluated by behavioral tests, followed by sacrifice and analysis of the liver-brain axis including histopathology, immunohistochemistry, and biochemical analyses. Histological analysis of the liver showed features of Metabolic Dysfunction-Associated Steatohepatitis (MASH) in the WD-fed mice including lipid droplet accumulation, inflammation, and fibrosis. This was accompanied by an elevation of transaminase and alkaline phosphatase activities, increase in inflammatory cytokine and bile acid concentrations, as well as altered amino acid concentrations in the blood. Interestingly, compromised blood capillary morphology coupled with astrogliosis and microgliosis were observed in brain hippocampus of the WD mice, indicating neuroinflammation or a disrupted neurovascular unit. Moreover, attention was impaired in WD-fed mice along with the observations of impaired motor activity and balance, enhanced anxiety, and stereotyped head-twitch response (HTR) behaviors. Analysis of neurotransmitters and modulators including dopamine, serotonin, GABA, glutamate, and acetylcholine showed region-specific dysregulation in the brain of the WD-fed mice. In conclusion, the induction of MASH in mice is accompanied by the alteration of cellular morphology and neurotransmitter expression in the brain, associated with compromised cognitive functions.


Assuntos
Dieta Ocidental , Fígado Gorduroso , Animais , Camundongos , Dieta Ocidental/efeitos adversos , Cognição , Encéfalo
14.
Diabetes ; 72(12): 1766-1780, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37725952

RESUMO

Maternal consumption of a Western-style diet (mWD) during pregnancy alters fatty acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact of these fetal adaptations and the pathways underlying disordered lipid metabolism are incompletely understood. Therefore, we tested whether a mWD chronically fed to lean, insulin-sensitive adult Japanese macaques throughout pregnancy and lactation would impact skeletal muscle oxidative capacity and lipid metabolism in adolescent offspring fed a postweaning (pw) Western-style diet (WD) or control diet (CD). Although body weight was not different, retroperitoneal fat mass and subscapular skinfold thickness were significantly higher in pwWD offspring consistent with elevated fasting insulin and glucose. Maximal complex I (CI)-dependent respiration in muscle was lower in mWD offspring in the presence of fatty acids, suggesting that mWD impacts muscle integration of lipid with nonlipid oxidation. Abundance of all five oxidative phosphorylation complexes and VDAC, but not ETF/ETFDH, were reduced with mWD, partially explaining the lower respiratory capacity with lipids. Muscle triglycerides increased with pwWD; however, the fold increase in lipid saturation, 1,2-diacylglycerides, and C18 ceramide compared between pwCD and pwWD was greatest in mWD offspring. Reductions in CI abundance and VDAC correlated with reduced markers of oxidative stress, suggesting that these reductions may be an early-life adaptation to mWD to mitigate excess reactive oxygen species. Altogether, mWD, independent of maternal obesity or insulin resistance, results in sustained metabolic reprogramming in offspring muscle despite a healthy diet intervention. ARTICLE HIGHLIGHTS: In lean, active adolescent offspring, a postweaning Western-style diet (pwWD) leads to shifts in body fat distribution that are associated with poorer insulin sensitivity. Fatty acid-linked oxidative metabolism was reduced in skeletal muscles from offspring exposed to maternal Western-style diet (mWD) even when weaned to a healthy control diet for years. Reduced oxidative phosphorylation complex I-V and VDAC1 abundance partially explain decreased skeletal muscle respiration in mWD offspring. Prior exposure to mWD results in greater fold increase with pwWD in saturated lipids and bioactive lipid molecules (i.e. ceramide and sphingomyelin) associated with insulin resistance.


Assuntos
Resistência à Insulina , Humanos , Animais , Gravidez , Feminino , Adolescente , Resistência à Insulina/fisiologia , Macaca fuscata/metabolismo , Metabolismo dos Lipídeos , Músculo Esquelético/metabolismo , Insulina/metabolismo , Dieta Ocidental/efeitos adversos , Ácidos Graxos/metabolismo , Ceramidas/metabolismo , Dieta Hiperlipídica
15.
Nutrients ; 15(18)2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37764680

RESUMO

The correlation between health and diet has always been a subject of interest in the field of dermatology and medicine in general. However, studies in the literature are still scarce, and need further investigation in the field of inflammatory skin diseases. In this paper, we report a case of a patient with atopic dermatitis whose complete recovery occurred only after combining dupilumab therapy with a Mediterranean diet regimen.


Assuntos
Dermatite Atópica , Dieta Mediterrânea , Humanos , Dermatite Atópica/etiologia , Dieta Ocidental/efeitos adversos
16.
J Nutr Sci Vitaminol (Tokyo) ; 69(4): 259-267, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37648512

RESUMO

Luteolin (LU), a natural compound, has diverse bioactivities; it alleviates lipid accumulation by enhancing the oxidation of fatty acids in nonalcoholic fatty liver disease (NAFLD). Mitochondrial dysfunction promotes the development of steatosis in NAFLD. However, few studies have focused on the mechanism by which LU affects mitochondrial function in NAFLD. In the present study, we investigated whether LU could ameliorate hepatic steatosis and affect mitochondrial function in Western diet-fed mice. After LU treatment, the indicators of hepatic function and markers of mitochondrial biogenesis were evaluated. The results showed that LU intervention 1) decreased the levels of serum triglyceride, total cholesterol, alanine aminotransferase, and low-density lipoprotein cholesterol; 2) increased the succinate dehydrogenase activity of mitochondrial enzyme; and 3) increased mitochondrial biogenesis by upregulating the AMPK/PGC-1α pathway. Therefore, LU might have the potential to prevent NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Proteínas Quinases Ativadas por AMP , Luteolina/farmacologia , Luteolina/uso terapêutico , Biogênese de Organelas , Dieta Ocidental/efeitos adversos , Colesterol
18.
Nutrients ; 15(15)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37571333

RESUMO

The study aimed to assess the associations of dietary patterns and circadian syndrome (CircS). Data from National Health and Nutrition Examination Survey (NHANES) 2005-2016 were analyzed (n = 10,486). Factor analysis was used to construct dietary patterns based on two 24 h food recalls. CircS was defined based on components of the metabolic syndrome, with the addition of short sleep and depression symptoms. Multivariable logistic regression was used to analyze the associations. Two major dietary patterns were identified. The Western dietary pattern had high loadings of refined grains, solid fats, added sugars, and red and cured meats, while the prudent pattern was characterized by a high intake of vegetables, whole grains, oils, nuts, and seeds. The prevalence of CircS was 41.3%. Comparing extreme quartiles of intake, the odds ratios (OR) for having CircS were 1.96 (95%CI 1.53-2.53) and 0.71 (95%CI 0.58-0.86) for the Western pattern and prudent pattern, respectively. The association between the Western dietary pattern and CircS was stronger among men (OR = 2.05; 95%CI 1.48-2.85) and those with low income (OR = 1.94; 95%CI 1.27-2.96) and high education (OR = 3.38; 95%CI 1.90-6.04). The Western dietary pattern was associated with a higher likelihood of having CircS, while the prudent pattern was inversely associated with CircS.


Assuntos
Dieta , Síndrome Metabólica , Masculino , Adulto , Humanos , Inquéritos Nutricionais , Verduras , Nozes , Dieta Ocidental/efeitos adversos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Fatores de Risco
19.
Nutrients ; 15(13)2023 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-37447184

RESUMO

Diet influences critical periods of growth, including gestation and early development. We hypothesized that a maternal/early life diet reflecting unprocessed dietary components would positively affect offspring metabolic and anthropometric parameters. Using 9 C57BL-6 dams, we simulated exposure to a Western diet, a high-fiber unprocessed diet (HFUD), or a control diet. The dams consumed their respective diets (Western [n = 3], HFUD [n = 3], and control [n = 3]) through 3 weeks of pregnancy and 3 weeks of weaning; their offspring consumed the diet of their mother for 4.5 weeks post weaning. Measurements included dual X-ray absorptiometry (DEXA) scans, feed consumption, body weight, blood glucose, and insulin and glycated hemoglobin (HbA1c) in the offspring. Statistical analyses included one-way ANOVA with Tukey's post hoc analysis. The offspring DEXA measures at 5 and 7.5 weeks post parturition revealed higher lean body mass development in the HFUD and control diet offspring compared to the Western diet offspring. An analysis indicated that blood glucose (p = 0.001) and HbA1c concentrations (p = 0.002) were lower among the HFUD offspring compared to the Western and control offspring. The results demonstrate that diet during gestation and early life consistent with traditional diet patterns may influence hyperglycemia and adiposity in offspring.


Assuntos
Dieta Ocidental , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Camundongos , Animais , Humanos , Dieta Ocidental/efeitos adversos , Glicemia/metabolismo , Hemoglobinas Glicadas , Camundongos Endogâmicos C57BL , Peso Corporal , Dieta , Avaliação de Resultados em Cuidados de Saúde , Dieta Hiperlipídica , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fenômenos Fisiológicos da Nutrição Materna
20.
Nutrients ; 15(13)2023 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-37447374

RESUMO

Background. The serotonin transporter (SERT), highly expressed in the gut and brain, is implicated in metabolic processes. A genetic variant of the upstream regulatory region of the SLC6A4 gene encoding SERT, the so-called short (s) allele, in comparison with the long (l) allele, results in the decreased function of this transporter, altered serotonergic regulation, an increased risk of psychiatric pathology and type-2 diabetes and obesity, especially in older women. Aged female mice with the complete (Sert-/-: KO) or partial (Sert+/-: HET) loss of SERT exhibit more pronounced negative effects following their exposure to a Western diet in comparison to wild-type (Sert+/+: WT) animals. Aims. We hypothesized that these effects might be mediated by an altered gut microbiota, which has been shown to influence serotonin metabolism. We performed V4 16S rRNA sequencing of the gut microbiota in 12-month-old WT, KO and HET female mice that were housed on a control or Western diet for three weeks. Results. The relative abundance of 11 genera was increased, and the abundance of 6 genera was decreased in the Western-diet-housed mice compared to the controls. There were correlations between the abundance of Streptococcus and Ruminococcaceae_UCG-014 and the expression of the pro-inflammatory marker Toll-like-Receptor 4 (Tlr4) in the dorsal raphe, as well as the expression of the mitochondrial activity marker perixome-proliferator-activated-receptor-cofactor-1b (Ppargc1b) in the prefrontal cortex. Although there was no significant impact of genotype on the microbiota in animals fed with the Control diet, there were significant interactions between diet and genotype. Following FDR correction, the Western diet increased the relative abundance of Intestinimonas and Atopostipes in the KO animals, which was not observed in the other groups. Erysipelatoclostridium abundance was increased by the Western diet in the WT group but not in HET or KO animals. Conclusions. The enhanced effects of a challenge with a Western diet in SERT-deficient mice include the altered representation of several gut genera, such as Intestinimonas, Atopostipes and Erysipelatoclostridium, which are also implicated in serotonergic and lipid metabolism. The manipulation of these genera may prove useful in individuals with the short SERT allele.


Assuntos
Microbioma Gastrointestinal , Proteínas da Membrana Plasmática de Transporte de Serotonina , Camundongos , Feminino , Animais , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Dieta Ocidental/efeitos adversos , RNA Ribossômico 16S/genética , Encéfalo/metabolismo , Firmicutes/metabolismo
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