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1.
Am J Physiol Endocrinol Metab ; 318(5): E830-E833, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: covidwho-101350

RESUMO

The angiotensin converting enzyme-2 (ACE2) cellular receptor is responsible for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus impacting the entrance and clearance of the virus. Studies demonstrate that upregulation of ACE2 has a protective effect on SARS-CoV-2 illness severity. Moreover, animal studies demonstrate that dietary intake can modulate ACE2 gene expression and function. A high intake of resveratrol may have a protective role, upregulating ACE2, whereas a high intake of dietary fat may have a detrimental role, downregulating ACE2. As such, we postulate on the biological plausibility of interactions between dietary fat and/or resveratrol and ACE2 gene variations in the modulation of SARS-CoV-2 illness severity. We call to action the research community to test this plausible interaction in a sample of human subjects.


Assuntos
Infecções por Coronavirus/fisiopatologia , Dieta , Gorduras na Dieta/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Pneumonia Viral/fisiopatologia , Resveratrol/farmacologia , Animais , Betacoronavirus/metabolismo , Feminino , Humanos , Masculino , Camundongos , Pandemias , Peptidil Dipeptidase A/metabolismo , Ratos , Índice de Gravidade de Doença
2.
Am J Physiol Endocrinol Metab ; 318(5): E830-E833, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32310688

RESUMO

The angiotensin converting enzyme-2 (ACE2) cellular receptor is responsible for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus impacting the entrance and clearance of the virus. Studies demonstrate that upregulation of ACE2 has a protective effect on SARS-CoV-2 illness severity. Moreover, animal studies demonstrate that dietary intake can modulate ACE2 gene expression and function. A high intake of resveratrol may have a protective role, upregulating ACE2, whereas a high intake of dietary fat may have a detrimental role, downregulating ACE2. As such, we postulate on the biological plausibility of interactions between dietary fat and/or resveratrol and ACE2 gene variations in the modulation of SARS-CoV-2 illness severity. We call to action the research community to test this plausible interaction in a sample of human subjects.


Assuntos
Infecções por Coronavirus/fisiopatologia , Dieta , Gorduras na Dieta/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Pneumonia Viral/fisiopatologia , Resveratrol/farmacologia , Animais , Betacoronavirus/metabolismo , Feminino , Humanos , Masculino , Camundongos , Pandemias , Peptidil Dipeptidase A/metabolismo , Ratos , Índice de Gravidade de Doença
3.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209700

RESUMO

BACKGROUND: The association of dietary fat distribution with markers of subclinical atherosclerosis during early life is unknown. We examined whether success in achieving the main target of an infancy-onset dietary intervention based on the distribution of dietary fat was associated with aortic and carotid intima-media thickness (IMT) and distensibility from childhood to young adulthood. METHODS: In the prospective randomized controlled Special Turku Coronary Risk Factor Intervention Project trial, personalized dietary counseling was given biannually to healthy children from infancy to young adulthood. The counseling was based on Nordic Nutrition Recommendations, with the main aim of improving the distribution of dietary fat in children's diets. IMT and distensibility of the abdominal aorta and common carotid artery were measured repeatedly at ages 11 (n = 439), 13 (n = 499), 15 (n = 506), 17 (n = 477), and 19 years (n = 429). The targeted distribution of dietary fat was defined as a ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids of <1:2 and as an intake of saturated fatty acids of <10% of energy intake. Participants who met ≥1 of these 2 criteria were defined to achieve the main intervention target. RESULTS: Individuals who achieved the main intervention target had lower aortic IMT (age- and sex-adjusted mean difference 10.4 µm; 95% confidence interval: 0.3 to 20.5 µm) and better aortic distensibility (0.13% per 10 mm Hg; 95% confidence interval: 0.00% to 0.26% per10 mm Hg) compared with their peers who did not meet the target. CONCLUSIONS: Achieving the main target of an infancy-onset dietary intervention, reflecting dietary guidelines, was favorably associated with aortic IMT and distensibility during the early life course. These data support the recommendation of favoring unsaturated fat to enhance arterial health.


Assuntos
Aterosclerose/prevenção & controle , Dieta com Restrição de Gorduras/métodos , Gorduras na Dieta/farmacologia , Ingestão de Energia/fisiologia , Adolescente , Aorta Torácica/diagnóstico por imagem , Aterosclerose/epidemiologia , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Criança , Aconselhamento , Progressão da Doença , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
4.
J Anim Sci ; 98(4)2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32215565

RESUMO

Fatty acids (FA) play a major role in relation to mucosal immune responses, epithelial barrier functions, oxidative stress, and inflammatory reactions. The dietary FA composition and the molecular structures (chain length and number of double bonds) influence digestion, absorption and metabolism, and the bioactivity of the FA. Piglets post-weaning having an immature intestine and not fully formed immune functions are very vulnerable to invading microorganisms. Manipulation of the milk FA composition via sow nutrition, or inclusion of dietary fat sources in the feed for newly weaned pigs, may be used as a strategic tool to enhance pig performance and their gut health and function pre- and post-weaning. Medium-chain fatty acids (MCFA) are absorbed directly into the portal blood and may contribute to immediate energy for the enterocytes. In addition, the MCFA, similarly to the short-chain fatty acids (SCFA), possess antibacterial effects and may thereby prevent overgrowth of pathogenic bacteria in the gastrointestinal tract. The essential FA, linoleic (LA) and α-linolenic (ALA) FA, form the building blocks for the long-chain polyunsaturated n-3 and n-6 FA. The conversion of ALA and LA into n-3 and n-6 eicosanoids, respectively, influences the molecular structures of metabolites and inflammatory reactions and other immune responses upon bacterial challenges. Dietary manipulation of the lactating sow influences the transfer of the n-3 and n-6 polyunsaturated fatty acids (PUFA) from the sow milk to the piglet and the incorporation of the FA into piglet enteric tissues and cell membranes, which exerts bioactivity of importance for immune responses and the epithelial barrier function. Especially, the n-3 PUFA present in fish oil seem to influence the gut health and function of pigs, and this is of importance during the transition periods such as post-weaning in which piglets are prone to inflammation. The proportion of unsaturated FA in the cell membranes influences the susceptibility to oxidative stress. Oxidative stress accompanies infectious diseases, and the development of lipid peroxides and other reactive oxygen products may be harmful to the epithelial barrier function. Fatty acid peroxides from the feed may also be absorbed with other lipid-solubles and thereby harm the intestinal function. Hence, antioxidative protection is important for the enteric cells. In conclusion, manipulation of the dietary FA composition can influence the gut health and function in pigs and may support a normal immune system and modulate resistance to infectious diseases during especially stressful phases of a pig's life such as post-weaning.


Assuntos
Ração Animal/análise , Dieta/veterinária , Gorduras na Dieta/farmacologia , Ácidos Graxos/química , Suínos/fisiologia , Desmame , Animais , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/análise , Ácidos Graxos/administração & dosagem
5.
J Anim Sci ; 98(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32047902

RESUMO

Pet foods may be formulated with decreased starch to meet consumer demands for less processed diets. Fats and oils may be added to low-starch diets to meet energy requirements, but little is known about its effects on canine health. The study objective was to evaluate the effects of feeding healthy adult dogs low carbohydrate, high-fat diets on apparent total tract digestibility, fecal characteristics, and overall health status. Eight adult Beagles were enrolled in a replicated 4 × 4 Latin Square design feeding trial. Dogs were randomly assigned to one of four dietary fat level treatments (T) within each period: 32% (T1), 37% (T2), 42% (T3), and 47% (T4) fat on a dry matter basis. Fat levels were adjusted with the inclusion of canola oil added to a commercial diet. Each dog was fed to exceed its energy requirement based on NRC (2006). Blood samples were analyzed for complete blood counts, chemistry profiles, and canine pancreatic lipase immunoreactivity levels. Apparent total tract digestibility improved (P < 0.05) as the fat level increased for dry matter, organic matter, fat, and gross energy. Fecal output decreased as levels of fat increased in the diet (P = 0.002). There was no effect of fat level on stool quality or short-chain fatty acid and ammonia concentrations in fecal samples (P ≥ 0.20). Blood urea nitrogen levels decreased with increased fat level (P = 0.035). No significant differences were seen in canine pancreatic lipase immunoreactivity (P = 0.110). All blood parameters remained within normal reference intervals. In summary, increased dietary fat improved apparent total tract digestibility, did not alter fecal characteristics, and maintained the health status of all dogs.


Assuntos
Ração Animal/análise , Dieta Hiperlipídica/veterinária , Gorduras na Dieta/farmacologia , Cães/fisiologia , Amônia/análise , Animais , Nitrogênio da Ureia Sanguínea , Dieta/veterinária , Digestão/efeitos dos fármacos , Cães/sangue , Ácidos Graxos Voláteis/análise , Fezes/química , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Nível de Saúde
6.
Am J Physiol Endocrinol Metab ; 318(2): E286-E296, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31891539

RESUMO

Increased myocardial partitioning of dietary fatty acids (DFA) and decreased left ventricular (LV) function is associated with insulin resistance in prediabetes. We hypothesized that enhanced myocardial DFA partitioning and reduced LV function might be induced concomitantly with reduced insulin sensitivity upon a 7-day hypercaloric (+50% in caloric intake), high-saturated fat (~11%energy), and simple carbohydrates (~54%energy) diet (HIGHCAL) versus an isocaloric diet (ISOCAL) with a moderate amount of saturated fat (~8%energy) and carbohydrates (~50%energy). Thirteen healthy subjects (7 men/6 women) underwent HIGHCAL versus ISOCAL in a randomized crossover design, with organ-specific DFA partitioning and LV function measured using the oral 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid and [11C]acetate positron emission tomography methods at the end of both interventions. HIGHCAL induced a decrease in insulin sensitivity indexes with no significant change in body composition. HIGHCAL led to increased subcutaneous abdominal (+4.2 ± 1.6%, P < 0.04) and thigh (+2.4 ± 1.2%, P < 0.08) adipose tissue storage and reduced cardiac (-0.31 ± 0.11 mean standard uptake value [(SUV), P < 0.03] and skeletal muscle (-0.17 ± 0.08 SUV, P < 0.05) DFA partitioning without change in LV function. We conclude that early increase in adipose tissue DFA storage protects the heart and skeletal muscles from potential deleterious effects of DFA.


Assuntos
Tecido Adiposo/metabolismo , Gorduras na Dieta/farmacologia , Ácidos Graxos/metabolismo , Hiperfagia/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Adulto , Composição Corporal , Estudos Cross-Over , Carboidratos da Dieta/farmacologia , Feminino , Voluntários Saudáveis , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Função Ventricular Esquerda/efeitos dos fármacos
7.
Oxid Med Cell Longev ; 2020: 8172714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998444

RESUMO

High-fat diet (HFD) often increases oxidative stress and enhances inflammatory status in the body. Toll-like receptor 4 (TLR4) is widely expressed in the pancreatic tissues and plays an important role in pancreatitis. This study is aimed at investigating the effect of HFD on acute pancreatitis (AP) and the role of TLR4-mediated necroptosis and inflammation in this disease. Weight-matched rats were allocated for an 8-week feeding on the standard chow diet (SCD) or HFD, and then, the AP model was induced by infusion of 5% sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at an indicated time point after modeling. Additionally, inhibition of TLR4 signaling by TAK-242 in HFD rats with AP was conducted in vivo. The results showed that the levels of serum free fatty acid (FFA) in HFD rats were higher than those in SCD rats. Moreover, HFD rats were more vulnerable to AP injury than SCD rats, as indicated by more serious pathological damage and much higher pancreatic malondialdehyde (MDA) and lipid peroxidation (LPO) levels as well as lower pancreatic superoxide dismutase (SOD) activities and reduced glutathione (GSH) contents and more intense infiltration of MPO-positive neutrophils and CD68-positive macrophages. In addition, HFD markedly increased the expressions of TLR4 and necroptosis marker (RIP3) and aggravated the activation of NF-κB p65 and the expression of TNF-α in the pancreas of AP rats at indicated time points. However, TLR4 inhibition significantly attenuated the structural and functional damage of the pancreas induced by AP in HFD rats, as indicated by improvement of the above indexes. Taken together, these findings suggest that HFD exacerbated the extent and severity of AP via oxidative stress, inflammatory response, and necroptosis. Inhibition of TLR4 signaling by TAK-242 alleviated oxidative stress and decreased inflammatory reaction and necroptosis, exerting a protective effect during AP in HFD rats.


Assuntos
Gorduras na Dieta/efeitos adversos , Necroptose/efeitos dos fármacos , Pancreatite/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Gorduras na Dieta/farmacologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pancreatite/patologia , Ratos , Ratos Sprague-Dawley , Sulfonamidas/farmacologia , Receptor 4 Toll-Like/antagonistas & inibidores
8.
J Nutr ; 150(5): 1041-1050, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31950177

RESUMO

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear. OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways. METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet (HSD; 20-10-70). Body composition was assessed weekly by EchoMRI. Whole-body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After 6 wk on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO), and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. Data were analyzed by ANOVA with data from the STD group included for references only. RESULTS: Compared with HCD and HSD, WD and HFD increased body fat mass 2.7- to 3.8-fold (P < 0.001), induced glucose intolerance (P < 0.001), and increased insulin concentrations >1.5-fold (P < 0.05), thereby enhancing basal and ISO-stimulated AKT phosphorylation at both threonine 308 and serine 473 residues (+25-63%; P < 0.05). Compared with HFD, the high-sugar diets potentiated ISO-mediated stimulation of the glucose-sensitive kinases PYK2 (>47%; P < 0.05 for HCD and HSD) and ERK (>34%; P < 0.05 for WD, HCD, and HSD), thereby leading to increased phosphorylation of protein synthesis regulator S6K1 at threonine 389 residue (>64%; P < 0.05 for WD, HCD, and HSD). CONCLUSIONS: Dietary fat and sugar affect cardiac growth signaling pathways in C57BL/6 mice through distinct and additive mechanisms. The findings may provide new insights into the role of overnutrition in pathological cardiac remodeling.


Assuntos
Gorduras na Dieta/farmacologia , Açúcares da Dieta/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Glicemia/efeitos dos fármacos , Gorduras na Dieta/administração & dosagem , Açúcares da Dieta/administração & dosagem , Ingestão de Energia , Regulação da Expressão Gênica/efeitos dos fármacos , Insulina Regular Humana/farmacologia , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL
9.
FASEB J ; 34(2): 2511-2523, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31908011

RESUMO

Nutritional status during intrauterine and/or early postnatal life has substantial influence on adult offspring health. Along these lines, there is a growing body of evidence illustrating that high fat diet (HFD)-induced maternal obesity can regulate fetal bone development. Thus, we investigated the effects of maternal obesity on both fetal skeletal development and mechanisms linking maternal obesity to osteoblast differentiation in offspring. Embryonic osteogenic calvarial cells (EOCCs) were isolated from fetuses at gestational day 18.5 (E18.5) of HFD-induced obese rat dams. We observed impaired differentiation of EOCCs to mature osteoblasts from HFD obese dams. ChIP-seq-based genome-wide localization of the repressive histone mark H3K27me3 (mediated via the polycomb histone methyltransferase, enhancer of zeste homologue 2 [Ezh2]) showed that this phenotype was associated with increased enrichment of H3K27me3 on the gene of SATB2, a critical transcription factor required for osteoblast differentiation. Knockdown of Ezh2 in EOCCs and ST2 cells increased SATB2 expression; while Ezh2 overexpression in EOCCs and ST2 cells decreased SATB2 expression. These data were consistent with experimental results showing strong association between H3K27me3, Ezh2, and SATB2 in cells from rats and humans. We have further presented that SATB2 mRNA and protein expression were increased in bones, and increased trabecular bone mass from pre-osteoblast specific Ezh2 deletion (Ezh2flox/flox Osx-Cre+ cko) mice compared with those from control Cre+ mice. These findings indicate that maternal HFD-induced obesity may be associated with decreasing fetal pre-osteoblastic cell differentiation, under epigenetic control of SATB2 expression via Ezh2-dependent mechanisms.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Feto , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas de Ligação à Região de Interação com a Matriz/biossíntese , Desenvolvimento Musculoesquelético/efeitos dos fármacos , Obesidade Materna , Osteoblastos , Fatores de Transcrição/biossíntese , Animais , Linhagem Celular , Gorduras na Dieta/farmacologia , Feminino , Feto/embriologia , Feto/patologia , Humanos , Obesidade Materna/induzido quimicamente , Obesidade Materna/metabolismo , Obesidade Materna/patologia , Osteoblastos/patologia , Gravidez , Ratos
10.
FASEB J ; 34(2): 2958-2967, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31908014

RESUMO

Fibrinogen-like-protein 1 (FGL1) is a novel hepatokine that plays an important role in hepatic steatosis and insulin resistance. Although FGL1 expression can be detected in adipose tissues, the functions of FGL1 in adipose tissues are still unknown. In this study, 356 participants with (body mass index (BMI) ≥25 kg/m2 ; n = 134) or without obesity (BMI <25 kg/m2 ; n = 222) were recruited, and we found that the plasma FGL1 concentrations were significantly higher in obese group than those of in the normal weight group, and were positively correlated with age, BMI, waist circumference, fat content, plasma glucose at 2 hours during an oral glucose tolerance test, and the insulin sensitivity index. In univariate analyses, BMI, waist circumference, total fat, visceral fat, and subcutaneous fat areas were positively correlated with FGL1 levels. After adjusting for age and gender, obesity indices, including the BMI and different fat areas, remained significantly associated with FGL1 levels. In order to investigate the causal relationship between FGL1 and obesity, animal and cell models were used. Overexpression of FGL1 in epididymal adipose tissue by lentiviral vector encoding FGL1 increased the fat pad size, whereas FGL1-knockdown by lentiviral vector encoding short-hairpin RNA targeted to FGL1 decreased high-fat diet-induced adiposity. In addition, 3T3-L1 adipocytes were used to clarify the possible mechanism of FGL1-induced adipogenesis. FGL1 induced adipogenesis through an ERK1/2-C/EBPß-dependent pathway in 3T3-L1 adipocytes. These findings highlight the pathophysiological role of FGL1 in obesity, and FGL1 might be a novel therapeutic target to combat obesity.


Assuntos
Adipócitos/metabolismo , Adipogenia , Tecido Adiposo/metabolismo , Fibrinogênio/metabolismo , Sistema de Sinalização das MAP Quinases , Obesidade/metabolismo , Células 3T3-L1 , Tecido Adiposo/patologia , Animais , Glicemia/genética , Glicemia/metabolismo , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Feminino , Fibrinogênio/antagonistas & inibidores , Fibrinogênio/genética , Humanos , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/genética , Obesidade/terapia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia
11.
Biomed Res Int ; 2020: 1315202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998777

RESUMO

Oleuropein and hydroxytyrosol, as major compounds of olive leaves, have been reported to exert numerous pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory activities. The purpose of this study is to evaluate and compare the protective effect of oleuropein- and hydroxytyrosol-rich extracts, derived from olive leaves, on high-fat diet-induced lipid metabolism disturbance and liver injury in rats. In this respect, four groups of male rats (8 per group) were used: control group (Control), group treated with high-fat diet (HFD), group treated with HFD and oleuropein (HFD + OLE), and group treated with HFD and hydroxytyrosol (HFD + HYD). The current research showed that the treatment with the HFD increased the body weight and adipose tissue mass in male rats. Moreover, the plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, and TNF-α were also raised. The hepatic immunohistochemical analysis revealed a significant increase in the expression of inflammatory genes (COX-2, NF-κB, and TNF-α). Equally, it showed a rise of the apoptotic markers (a decrease in the expression of the Bcl-2 and an increase of the P53). In addition, the oral administration of oleuropein- and hydroxytyrosol-rich olive leaf extracts at 16 mg/kg similarly reduced the body weight and adipose tissue mass and improved the lipid profile. Moreover, these extracts, mainly the hydroxytyrosol-rich extract, reduced the elevated liver enzymes, enhanced the antioxidant status, and attenuated the liver inflammation and apoptosis. These findings suggest that the oleuropein- and hydroxytyrosol-rich olive leaf extracts possessed hypolipidemic and hepatoprotective effects against the HFD-induced metabolic disorders by enhancing the antioxidative defense system and blocking the expression of the proteins involved in inflammation and liver damage.


Assuntos
Gorduras na Dieta/efeitos adversos , Iridoides/farmacologia , Hepatopatias , Fígado , Olea/química , Álcool Feniletílico/análogos & derivados , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Gorduras na Dieta/farmacologia , Iridoides/química , Metabolismo dos Lipídeos , Fígado/lesões , Fígado/metabolismo , Fígado/patologia , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Extratos Vegetais/química , Ratos
12.
Am J Physiol Endocrinol Metab ; 318(3): E417-E429, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31910028

RESUMO

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m2] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m2) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher (P < 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 (P = 0.06) and ceramide C16:0 (P < 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.


Assuntos
Gorduras na Dieta/farmacologia , Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Sobrepeso/metabolismo , Período Pós-Prandial , Aminoácidos/metabolismo , Estudos Cross-Over , Glucose/metabolismo , Humanos , Hiperfagia , Resistência à Insulina , Cinética , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Proteínas do Leite/farmacologia , Músculo Esquelético/efeitos dos fármacos
13.
Artigo em Inglês | MEDLINE | ID: mdl-31461687

RESUMO

The present study was performed to determine the effect of high fat diet in lipid accumulation, oxidative stress and autophagy, and to explore the underlying molecular mechanism of high fat diet induced hepatic oxidative damage in Chinese softshell turtle. To this end, the control group were fed a normal fat diet (NFD, 6.38% lipid) and the experimental group were bred high fat diet (HFD, 13.89% lipid) for eight weeks. Lipid accumulation, oxidative stress and autophagy, as well as the mRNA expression of genes related to the antioxidant system were determined in the liver. Results showed that high fat diet not only exacerbated lipid accumulation in the liver and serum through increasing contents of triglyceride, total cholesterol and low-density lipoprotein and decreasing content of high-density lipoprotein, but also induced liver injury through increasing activities of alanine aminotransferase and aspartate aminotransferase in the serum. In addition, the experimental subject induced oxidative injury for the increase of reactive oxygen species, malondialdehyde and protein carbonyl contents and the reduction of glutathione contents, anti-superoxide anion capacity and catalase, total superoxide dismutase, glutathione peroxidase, glutathione-S transferase activities. Meanwhile, antioxidant-related signaling molecule expression were also decreased, which might attribute to regulate antioxidant-related signaling molecule. On top of that, it indicated promote the occurrence of liver autophagy via up-regulating expressions of AMP activated protein kinase, UNC-51-like kinase 1, Microtubule-associated proteins 1A/1B light chain 3 and down-regulating gene expression of mammalian target of rapamycin. In conclusion, high fat diet could enhance lipid accumulation in the liver and serum, lead to liver injury and oxidative damage, impair liver antioxidant capacity, regulate antioxidant-related signaling molecule expression and activate hepatic autophagy.


Assuntos
Morte Celular Autofágica/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tartarugas/metabolismo , Animais , Gorduras na Dieta/farmacologia , Fígado/patologia
14.
Metabolism ; 103: 154041, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785256

RESUMO

BACKGROUND: Our previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans. PURPOSE: The purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation. METHODS: Thirteen normal weight young adult males (BMI 23.1 ±â€¯0.8 kg/m2, age 22.2 ±â€¯0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD. MAIN FINDINGS: Intestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (-24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD. CONCLUSION: These findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity.


Assuntos
Adaptação Fisiológica/fisiologia , Dieta Hiperlipídica , Endotoxinas/sangue , Mucosa Intestinal/metabolismo , Músculo Esquelético/metabolismo , Adulto , Gorduras na Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Permeabilidade , Adulto Jovem
15.
Mol Cell Biochem ; 465(1-2): 125-139, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838625

RESUMO

Our previous studies have confirmed that proline/serine-rich coiled-coil 1 (PSRC1) overexpression can regulate blood lipid levels and inhibit atherosclerosis (AS) development. In the current study, the gene and transcript expression profiles in the livers of ApoE-/- mice overexpressing PSRC1 were investigated. HiSeq X Ten RNA sequencing (RNA-seq) analysis was used to examine the differentially expressed genes (DEGs) and differentially expressed transcripts in the livers of PSRC1-overexpressing ApoE-/- and control mice. Then, Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these DEGs and on long noncoding RNA (lncRNA) predicted target genes. A total of 1892 significant DEGs were identified: 1431 were upregulated (e.g., Cyp2a4, Obp2a, and Sertad4), and 461 were downregulated (e.g., Moxd1, Egr1, and Elovl3). In addition, 8184 significant differentially expressed transcripts were identified, 4908 of which were upregulated and 3276 of which were downregulated. Furthermore, 1106 significant differentially expressed lncRNAs were detected, 713 of which were upregulated and 393 of which were downregulated. Quantitative reverse transcription PCR (qRT-PCR) verified changes in 10 randomly selected DEGs. GO analyses showed that the DEGs and predicted lncRNA target genes were mostly enriched for actin binding and lipid metabolism. KEGG biological pathway analyses showed that the DEGs in the livers of PSRC1-overexpressing ApoE-/- mice were enriched in the mitogen-activated protein kinase (MAPK) pathway. These findings reveal that PSRC1 may affect liver actin polymerization and cholesterol metabolism-related genes or pathways. These mRNAs and lncRNAs may represent new biomarkers and targets for the diagnosis and therapy of lipid metabolism disturbance and AS.


Assuntos
Aterosclerose , Gorduras na Dieta/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfoproteínas/biossíntese , Animais , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Gorduras na Dieta/farmacologia , Perfilação da Expressão Gênica , Camundongos , Camundongos Knockout para ApoE , Fosfoproteínas/genética
16.
Artigo em Inglês | MEDLINE | ID: mdl-31669375

RESUMO

Elongation of very long-chain fatty acid 4 (Elovl4) proteins are involved in the biosynthesis of very long-chain (>C24) fatty acids and in many teleost fish species they are key enzymes in the pathway for the production of docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Therefore, Elovl4 may be particularly important in Atlantic bluefin tuna (ABT; Thunnus thynnus) characterised by having high DHA to EPA ratios. The present study cloned and characterised both the function and expression of an elovl4 cDNA from ABT. The Elovl4 had an open reading frame of 915 base pairs encoding a putative protein of 304 amino acids. Alignment and phylogenetic analyses indicated that the Elovl4 isoform identified in the present study was an Elovl4b. Functional characterisation demonstrated that the Elovl4b enzyme had elongase activity towards all the polyunsaturated fatty acid (PUFA) substrates assayed. The ABT Elovl4b contributed to DHA biosynthesis by elongation of EPA and DPA to 24:5n-3, the latter being desaturated to 24:6n-3 by the action of fads2 (Δ6 desaturase). Additionally, the ABT Elovl4b has a role in the biosynthesis of very long-chain PUFA up to C34, compounds of key structural roles in neural tissues such as eye and brain, which had high levels of elovl4b transcripts. Surprisingly, while the relative expression of fads2, required for the production of DHA from EPA, was increased in liver of ABT fed a diet with reduced levels of EPA and DHA, expression of elovl4b was reduced. Results indicated that ABT has enzymes necessary for endogenous production of DHA from EPA and demonstrate that Elovl4b can effectively compensate for absence of Elovl2.


Assuntos
Clonagem Molecular , Gorduras na Dieta/farmacologia , Elongases de Ácidos Graxos , Proteínas de Peixes , Regulação da Expressão Gênica/efeitos dos fármacos , Atum , Animais , Elongases de Ácidos Graxos/biossíntese , Elongases de Ácidos Graxos/genética , Proteínas de Peixes/biossíntese , Proteínas de Peixes/genética , Atum/genética , Atum/metabolismo
17.
Metabolism ; 102: 153996, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678069

RESUMO

BACKGROUND: We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS: We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS: Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ±â€¯0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ±â€¯0.17], 10 overweight (BMI: 27.1 ±â€¯0.5; HOMAIR: 1.25 ±â€¯0.11), and 10 obese (BMI: 35.9 ±â€¯1.3; HOMAIR: 5.82 ±â€¯0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS: Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS: These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.


Assuntos
Proteínas Sanguíneas/metabolismo , Ingestão de Alimentos/fisiologia , Carne , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Fosfotransferases (Aceptor do Grupo Fosfato)/metabolismo , Proteoma/metabolismo , Adulto , Fatores Etários , Proteínas Sanguíneas/análise , Índice de Massa Corporal , Gorduras na Dieta/farmacologia , Metabolismo Energético/fisiologia , Feminino , Glucose/metabolismo , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/análise , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Obesidade/sangue , Obesidade/patologia , Fosfotransferases (Aceptor do Grupo Fosfato)/análise , Período Pós-Prandial/fisiologia , Proteoma/análise , Magreza/sangue , Magreza/metabolismo , Magreza/patologia , Adulto Jovem
18.
J Cell Physiol ; 235(2): 1065-1075, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264208

RESUMO

Chronic high-fat-diet (HFD) consumption can lead to the development of brain insulin resistance, which then exerts deleterious effects on learning and memory. Activity-regulated cytoskeleton-associated protein (Arc) is a memory-related protein, and its expression can be induced by insulin stimulation. In HFD-fed animals, their basal Arc protein levels in cerebral cortex and hippocampus are reduced. However, the effects of HFD on novelty-induced Arc protein expression that is important for cognitive function is still unknown. In the present study, after feeding HFD (60% kcal from fat) for 5 weeks, mice developed brain insulin resistance and had a significant reduction in the novelty-induced but not the basal Arc protein levels in their hippocampi. Further experiments were performed in primary rat hippocampal neurons. The results show that, under the condition of neuronal insulin resistance, acute insulin stimulation induced less activation of the phosphatidylinositol 3-kinase/protein kinase B/p70 ribosomal S6 kinase (PI3K/Akt/p70S6K) pathway, resulting in reduced induction of Arc protein expression. Accordingly, it is suggested that following HFD feeding, the reduction in novelty-induced Arc protein expression in animal's hippocampus is probably related to a suppressed activation of the PI3K/Akt/p70S6K pathway due to the existence of brain insulin resistance.


Assuntos
Proteínas do Citoesqueleto/metabolismo , Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Ração Animal/análise , Animais , Células Cultivadas , Proteínas do Citoesqueleto/genética , Hipocampo/citologia , Insulina/farmacologia , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/genética , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
19.
Lipids Health Dis ; 18(1): 209, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796080

RESUMO

BACKGROUND: Consumption of a Western-styled diet enriched in saturated fatty acids (SFA) relative to polyunsaturated fatty acids is positively associated with risk for Alzheimer's disease. Whilst potential causal mechanism are unclear, there is increasing evidence that chronic ingestion of SFA enriched diets promote increase the plasma levels of lipoprotein-associated amyloid-ß (Aß). However, the effects of dietary mono- and poly-unsaturated fats (MUFA/PUFA) on nascent lipoprotein Aß abundance have not been previously reported. METHODS: Wild-type C57BL/6 J mice were maintained on low-fat control chow (LF) or diets enriched in either SFA, MUFA, or PUFA for 9 months. Enterocytic abundance of Aß was determined with quantitative immunofluorescent microscopy and plasma Aß was measured by ELISA. RESULTS: The chronic ingestion of SFA-enriched diet increased the enterocytic abundance and plasma concentration of Aß compared to LF control mice. The mice maintained on MUFA or PUFA diet showed comparable enterocytic and plasma Aß levels to the LF control mice. CONCLUSIONS: The data indicates that a diet enriched in SFA significantly increases the enterocytic Aß production and secretion into the circulation, whilst MUFA and PUFA enriched diet do not exert such effects.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Gorduras na Dieta/farmacologia , Enterócitos/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos/farmacologia , Peptídeos beta-Amiloides/química , Animais , Enterócitos/metabolismo , Enterócitos/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Camundongos , Camundongos Endogâmicos C57BL
20.
Curr Gastroenterol Rep ; 21(11): 62, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792624

RESUMO

PURPOSE OF REVIEW: To review recent data on the role and interactions of fiber and fat as dietary risk factors associated with colorectal cancer (CRC) risk in humans. RECENT FINDINGS: Fiber intake shows convincing and linear dose-response negative correlation with CRC risk. Dietary fiber stimulates butyrogenic activity of the gut microbiota, providing high amounts of butyrate that shows extensive anti-neoplastic effects. A high-fat diet promotes CRC risk through stimulated bile acid metabolism, facilitating bile acid conversion by the gut microbiota to tumor-promoting deoxycholic acid. Comprehensive interactions of these microbial metabolites are likely to underlie mechanisms driving diet-dependent CRC risk in different populations, but require further experimental investigation. Dietary fiber and fat shape the composition and metabolic function of the gut microbiota, resulting in altered amounts of butyrate and deoxycholic acid in the colon. Fiber supplementation and restriction of fat intake represent promising strategies to reduce CRC risk in healthy individuals.


Assuntos
Neoplasias Colorretais/etiologia , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Ácidos e Sais Biliares/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/prevenção & controle , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Humanos , Fatores de Risco
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