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1.
J Sci Food Agric ; 101(15): 6417-6423, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33982308

RESUMO

BACKGROUND: Rice α-globulin has been reported to have serum cholesterol-lowering activity in rats. However, it is still unclear whether α-globulin exerts this effect when taken as one of the dietary components. In the present study, we investigated the effect of two cultivars of rice, low glutelin content (LGC)-1 and LGC-Jun, on reducing serum cholesterol in exogenously hypercholesterolemic (ExHC) rats. LGC-1 is enriched in α-globulin (10.6 mg g-1 rice flour, which is an approximately 1.5 times higher α-globulin content than in Koshihikari a predominant rice cultivar in Japan), whereas LGC-Jun is a globulin-negative cultivar. METHODS: ExHC rats, the model strain of diet-induced hypercholesterolemia, were fed 50% LGC-1 or LGC-Jun and 0.5% cholesterol-containing diets for 2 weeks, followed by measurement of cholesterol metabolism parameters in serum and tissues. RESULTS: Serum cholesterol and non-high-density lipoprotein cholesterol levels were significantly lower in the LGC-1 group compared to the LGC-Jun group. Cholesterol intestinal absorption markers, hepatic and serum levels of campesterol and ß-sitosterol, and lymphatic cholesterol transport were not different between the two groups. Levels of 7α-hydroxycholesterol, an intermediate of bile acid synthesis, showed a downward trend in the livers of rats that were fed LGC-1 (P = 0.098). There was a significant decrease in the hepatic mRNA expression of Cyp7a1 (a synthetic enzyme for 7α-hydroxycholesterol) in the LGC-1 group compared to the LGC-Jun group. CONCLUSION: Dietary LGC-1 significantly decreased serum cholesterol levels in ExHC rats. The possible mechanism for the cholesterol-lowering activity of LGC-1 is partial inhibition of bile acid and cholesterol synthesis in the liver. © 2021 Society of Chemical Industry.


Assuntos
alfa-Globulinas/análise , Colesterol/sangue , Glutens/análise , Hipercolesterolemia/dietoterapia , Oryza/metabolismo , Proteínas de Plantas/análise , alfa-Globulinas/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Glutens/metabolismo , Humanos , Hipercolesterolemia/sangue , Fígado/metabolismo , Masculino , Oryza/química , Oryza/classificação , Proteínas de Plantas/metabolismo , Ratos , Ratos Sprague-Dawley
2.
Plant Physiol ; 178(3): 1358-1369, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30266749

RESUMO

Under high light intensity, chloroplasts avoid absorbing excess light by moving to anticlinal cell walls (avoidance response), but under low light intensity, chloroplasts accumulate along periclinal cell walls (accumulation response). In most plant species, these responses are induced by blue light and are mediated by the blue light photoreceptor, phototropin, which also regulates phototropism, leaf flattening, and stomatal opening. These phototropin-mediated responses could enhance photosynthesis and biomass production. Here, using various Arabidopsis (Arabidopsis thaliana) mutants deficient in chloroplast movement, we demonstrated that the accumulation response enhances leaf photosynthesis and plant biomass production. Conspicuously, phototropin2 mutant plants specifically defective in the avoidance response but not in other phototropin-mediated responses displayed a constitutive accumulation response irrespective of light intensities, enhanced leaf photosynthesis, and increased plant biomass production. Therefore, our findings provide clear experimental evidence of the importance of the chloroplast accumulation response in leaf photosynthesis and biomass production.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Fotossíntese/fisiologia , Fototropinas/metabolismo , Fototropismo/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Biomassa , Cloroplastos/metabolismo , Fototropinas/genética , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Estômatos de Plantas/genética , Estômatos de Plantas/crescimento & desenvolvimento , Estômatos de Plantas/fisiologia
3.
Cardiovasc Drugs Ther ; 33(1): 35-44, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30671747

RESUMO

PURPOSE: Oxycholesterols (OCs) are produced from cholesterol by oxidation of the steroidal backbone and side-chain. OCs are present in blood and evidence suggests their involvement in disease development and progression. However, limited information is available regarding the absorption mechanisms and relative absorption rates of dietary OCs. Although ezetimibe is known to inhibit intestinal cholesterol absorption via Niemann-Pick C1-Like 1 (NPC1L1), whether it also inhibits dietary OC absorption is unclear. METHODS: We investigated the effects of ezetimibe on OC absorption in rats fed an OC-rich diet containing 10 different OCs. We collected lymphatic fluid using permanent cannulation of the thoracic duct and quantified OC levels. RESULTS: Ezetimibe treatment significantly reduced the apparent absorption of 5ß,6ß-epoxycholesterol (5,6ß-epoxy) and its levels in the proximal intestinal mucosa in OC-fed rats. Using in silico analyses, the binding energy of NPC1L1 N-terminal domain (NPC1L1-NTD) and 5,6ß-epoxy was found to be similar to that of NPC1L1-NTD and cholesterol, suggesting that polar uncharged amino acids located in the steroidal part of 5,6ß-epoxy were involved. CONCLUSION: Our results indicate that ezetimibe-mediated inhibition of dietary OC absorption varies depending on the specific OC, and only the absorption of 5,6ß-epoxy is significantly reduced.


Assuntos
Anticolesterolemiantes/farmacologia , Colesterol/análogos & derivados , Dieta , Ezetimiba/farmacologia , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Administração Oral , Ração Animal , Animais , Colesterol/administração & dosagem , Colesterol/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Proteínas de Membrana Transportadoras/metabolismo , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Ducto Torácico/efeitos dos fármacos , Ducto Torácico/metabolismo
4.
Br J Nutr ; 119(9): 970-980, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29532765

RESUMO

Diabetes mellitus is a metabolic disease spreading worldwide that has been reported to worsen the development and progression of other diseases (cancer, vascular diseases and dementia). To establish functional rice lines with anti-postprandial hyperglycaemic effects, we developed mutant rice lines, which lack one or two gene(s) related to starch synthesis, and evaluated their effects. Powder of mutant rice lines or other grains was loaded to rats fasted overnight (oral grain powder loading test). Incremental area under time-concentration curves (iAUC) were calculated with monitored blood glucose levels. Rice lines with anti-postprandial hyperglycaemic effects were separated by cluster analysis with calculated iAUC. A double mutant rice #4019 (starch synthase IIIa (ss3a)/branching enzyme IIb (be2b)), one of the screened mutant rice lines, was fed to Goto-Kakizaki (GK) rats, an animal model for type 2 diabetes, for 5 weeks. Plasma levels of C-peptide, a marker of pancreatic insulin secretion, were measured with ELISA. For in vitro study, a rat pancreatic cell line was cultured with a medium containing rat serum which was sampled from rats fed #4019 diet for 2 d. After 24-h of incubation, an insulin secretion test was performed. Through the oral rice powder loading test, seven rice lines were identified as antidiabetic rice lines. The intake of #4019 diet increased plasma C-peptide levels of GK rats. This result was also observed in vitro. In rat serum added to cell medium, ornithine was significantly increased by the intake of #4019. In conclusion, the mutant rice #4019 promoted pancreatic insulin secretion via elevation of serum ornithine levels.


Assuntos
Enzima Ramificadora de 1,4-alfa-Glucana/genética , Diabetes Mellitus Tipo 2/prevenção & controle , Hipoglicemiantes/farmacologia , Secreção de Insulina/genética , Oryza/genética , Sintase do Amido/genética , Enzima Ramificadora de 1,4-alfa-Glucana/deficiência , Enzima Ramificadora de 1,4-alfa-Glucana/metabolismo , Ração Animal , Animais , Área Sob a Curva , Glicemia , Análise por Conglomerados , Diabetes Mellitus Tipo 2/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Teste de Tolerância a Glucose , Glicilglicina/sangue , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Masculino , Mutação , Ornitina/sangue , Oryza/classificação , Oryza/enzimologia , Oryza/metabolismo , Pâncreas/metabolismo , Ratos , Ratos Sprague-Dawley , Sintase do Amido/deficiência , Sintase do Amido/metabolismo
5.
Br J Nutr ; 118(6): 423-430, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28980893

RESUMO

Egg-white protein (EWP) is known to reduce lymphatic TAG transport in rats. In this study, we investigated the effects of dietary EWP on body fat mass. Male rats, 4 weeks old, were fed diets containing either 20 % EWP or casein for 28 d. Carcass protein levels and gastrocnemius leg muscle weights in the EWP group were significantly higher than those in the casein group. In addition, carcass TAG levels and abdominal fat weights in the EWP group were significantly lower than those in the casein group; adipocyte size in abdominal fat in the EWP group was smaller than that in the casein group. To identify the involvement of dietary fat levels in the rats, one of two fat levels (5 or 10 %) was added to their diet along with the different protein sources (EWP and casein). Abdominal fat weight and serum and hepatic TAG levels were significantly lower in the EWP group than in the casein group. Moreover, significantly higher values of enzymatic activity related to ß-oxidation in the liver were observed in the EWP group compared with the casein group. Finally, abdominal fat weight reduction in the EWP group with the 10 % fat diet was lower than that in the EWP group with the 5 % fat diet. In conclusion, our results indicate that, in addition to the inhibition of dietary TAG absorption reported previously, dietary EWP reduces body fat mass in rats through an increase of body protein mass and the acceleration of ß-oxidation in the liver.


Assuntos
Adiposidade , Proteínas Dietéticas do Ovo/administração & dosagem , Fígado/metabolismo , Músculo Esquelético/fisiologia , Gordura Abdominal/metabolismo , Adipócitos/metabolismo , Animais , Composição Corporal , Índice de Massa Corporal , Caseínas/administração & dosagem , Dieta , Gorduras na Dieta/administração & dosagem , Clara de Ovo/química , Metabolismo dos Lipídeos , Masculino , Tamanho do Órgão/fisiologia , Ratos , Ratos Sprague-Dawley , Triglicerídeos/sangue
6.
Br J Nutr ; 116(3): 451-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27267802

RESUMO

Probiotic Lactobacillus gasseri SBT2055 (LG2055) reduces postprandial TAG absorption and exerts anti-obesity effects in rats and humans; however, the underlying mechanisms are not fully understood. In the present study, we addressed the mechanistic insights of the anti-obesity activity of LG2055 by feeding Sprague-Dawley rats diets containing skimmed milk fermented or not by LG2055 for 4 weeks and by analysing energy expenditure, glucose tolerance, the levels of SCFA in the caecum and serum inflammatory markers. Rats fed the LG2055-containing diet demonstrated significantly higher carbohydrate oxidation in the dark cycle (active phase for rats) compared with the control group, which resulted in a significant increase in energy expenditure. LG2055 significantly reduced cumulative blood glucose levels (AUC) compared with the control diet after 3 weeks and increased the molar ratio of butyrate:total SCFA in the caecum after 4 weeks. Furthermore, the LG2055-supplemented diet significantly reduced the levels of serum amyloid P component - an indicator of the inflammatory process. In conclusion, our results demonstrate that, in addition to the inhibition of dietary TAG absorption reported previously, the intake of probiotic LG2055 enhanced energy expenditure via carbohydrate oxidation, improved glucose tolerance and attenuated inflammation, suggesting multiple additive and/or synergistic actions underlying the anti-obesity effects exerted by LG2055.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Glicemia/metabolismo , Metabolismo Energético , Lactobacillus gasseri , Obesidade/prevenção & controle , Probióticos/uso terapêutico , Aumento de Peso , Animais , Área Sob a Curva , Butiratos/metabolismo , Metabolismo dos Carboidratos , Ceco/metabolismo , Produtos Fermentados do Leite/microbiologia , Dieta , Ácidos Graxos Voláteis/metabolismo , Inflamação/sangue , Inflamação/prevenção & controle , Metabolismo dos Lipídeos , Masculino , Ratos Sprague-Dawley , Componente Amiloide P Sérico/metabolismo , Triglicerídeos/sangue
7.
Lipids Health Dis ; 13: 36, 2014 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-24548293

RESUMO

BACKGROUND: Lactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals. METHODS: We conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured. RESULTS: The OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period. CONCLUSIONS: The consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus. TRIAL REGISTRATION: UMIN000011605.


Assuntos
Ácidos Graxos não Esterificados/sangue , Hipertrigliceridemia/terapia , Lactobacillus/fisiologia , Probióticos/administração & dosagem , Produtos Fermentados do Leite/microbiologia , Jejum/sangue , Feminino , Humanos , Hipertrigliceridemia/sangue , Japão , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Método Simples-Cego , Resultado do Tratamento , Triglicerídeos/sangue
8.
Metabolites ; 14(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38921456

RESUMO

Previous studies have shown that dietary cholest-4-en-3-one (4-cholestenone, 4-STN) exerts anti-obesity and lipid-lowering effects in mice. However, its underlying mechanisms are not fully understood. In the present study, we evaluated whether 4-STN supplementation would protect obese diabetic db/db mice from obesity-related metabolic disorders. After four weeks of feeding of a 0.25% 4-STN-containing diet, dietary 4-STN was found to have significantly alleviated hyperlipidemia, hepatic cholesterol accumulation, and hyperinsulinemia; however, the effect was not sufficient to improve hepatic triglyceride accumulation or obesity. Further analysis demonstrated that dietary 4-STN significantly increased the content of free fatty acids and neutral steroids in the feces of db/db mice, indicating that the alleviation of hyperlipidemia by 4-STN was due to an increase in lipid excretion. In addition, dietary 4-STN significantly reduced the levels of desmosterol, a cholesterol precursor, in the plasma but not in the liver, suggesting that normalization of cholesterol metabolism by 4-STN is partly attributable to the suppression of cholesterol synthesis in extrahepatic tissues. In addition, dietary 4-STN increased the plasma and hepatic levels of 4-STN metabolites cholestanol (5α-cholestan-3ß-ol) and coprostanol (5ß-cholestan-3ß-ol). Our results show that dietary 4-STN alleviates obesity-related metabolic disorders, such as hyperlipidemia, hepatic cholesterol accumulation, and hyperinsulinemia, in db/db mice.

9.
Lipids Health Dis ; 12: 18, 2013 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-23406154

RESUMO

BACKGROUND: Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice. RESULTS: After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet. CONCLUSION: The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mice.


Assuntos
Agaricales/química , Diabetes Mellitus/tratamento farmacológico , Carpóforos/química , Hepatomegalia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Obesidade/tratamento farmacológico , Pós/farmacologia , Animais , Carnitina O-Palmitoiltransferase/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Mellitus/metabolismo , Ácido Graxo Sintases/metabolismo , Alimentos Formulados , Glucosefosfato Desidrogenase/metabolismo , Hepatomegalia/metabolismo , Hiperlipidemias/metabolismo , Leptina/deficiência , Leptina/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Obesidade/metabolismo , Fosfatidato Fosfatase/metabolismo , Pós/química , Triglicerídeos/metabolismo
10.
Lipids Health Dis ; 12: 134, 2013 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-24034595

RESUMO

BACKGROUND: Nutritional guidance and diet control play important roles in the treatment of obesity and non-alcoholic fatty liver. However, in Japan, nutritional guidance is difficult to provide in practice. Therefore, we evaluated the effects of providing the 'once-a-day' intervention of a healthy lunch on various metabolic parameters. METHODS: For a 1-month preparatory period, 10 subjects generally consumed the lunches that were provided by the worksite cafeteria. This was followed by a 1-week washout period, after which, the subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test period. After the preparatory and test periods, blood samples were obtained from all subjects. The serum levels of indices relevant to metabolic syndrome and fatty liver were measured. RESULTS: Serum alanine aminotransferase activity significantly decreased by 20.3% after the healthy intervention. However, the indices of metabolic syndrome did not significantly change. Analysis of the relationship between serum alanine aminotransferase activity and nutrient content indicated that the improvement of serum alanine aminotransferase status was due to the higher vegetable content and lower animal-source protein of the meals provided. CONCLUSIONS: In summary, the 'once-a-day' intervention of providing a healthy lunch improved serum alanine aminotransferase status. A diet high in vegetables and low in animal-based protein is important in maintaining a healthy condition.


Assuntos
Alanina Transaminase/sangue , Restrição Calórica , Dislipidemias/enzimologia , Hipertensão/enzimologia , Adulto , Índice de Massa Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/dietoterapia , Ingestão de Alimentos , Ingestão de Energia , Humanos , Hipertensão/sangue , Hipertensão/dietoterapia , Japão , Almoço , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Verduras/metabolismo
11.
J Oleo Sci ; 72(1): 99-104, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36624060

RESUMO

This study aimed to investigate the effects of interleukin-25, which belongs to the interleukin-17 family, on short-term high-fructose diet-induced hepatic triacylglycerol accumulation. Rats were fed a high-starch (control) or high-fructose diet for 7 d, with or without intraperitoneal administration of recombinant interleukin-25 from days 3-7. Treatment with interleukin-25 significantly reduced the mRNA levels and activity of fatty acid synthesis enzymes and caused a nominal reduction in hepatic triacylglycerol levels in rats fed a high-fructose diet but not in those fed a control diet. Interleukin-25 treatment did not affect the mRNA levels of ß-oxidation enzymes in either the control or fructose-fed rats. These results suggest that treatment with interleukin-25 suppresses short-term high-fructose diet-induced fatty acid synthesis and leads to the alleviation of triacylglycerol accumulation in the liver.


Assuntos
Frutose , Interleucina-17 , Fígado , Animais , Ratos , Dieta , Ácidos Graxos/metabolismo , Frutose/farmacologia , Expressão Gênica , Interleucina-17/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ratos Wistar , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo
12.
Metabolites ; 13(3)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36984876

RESUMO

Microalgae are attracting attention as a next-generation alternative source of protein and essential fatty acids that do not consume large amounts of water or land. Chaetoceros gracilis (C. gracilis)-a marine microalga-is rich in proteins, fucoxanthin, and eicosapentaenoic acid (EPA). Growing evidence indicates that dietary fucoxanthin and EPA have beneficial effects in humans. However, none of these studies have shown that dietary C. gracilis has beneficial effects in mammals. In this study, we investigated the effects of dietary C. gracilis on lipid abnormalities in Sprague-Dawley rats fed a high-sucrose cholesterol-containing diet. Dried C. gracilis was added to the control diet at a final dose of 2 or 5% (w/w). After four weeks, the soleus muscle weights were found to be dose-responsive to C. gracilis and showed a tendency to increase. The hepatic triglyceride and total cholesterol levels were significantly reduced by C. gracilis feeding compared to those in the control group. The activities of FAS and G6PDH, which are related to fatty acid de novo synthesis, were found to be dose-responsive to C. gracilis and tended to decrease. The hepatic glycerol content was also significantly decreased by C. gracilis feeding, and the serum HDL cholesterol levels were significantly increased, whereas the serum levels of cholesterol absorption markers (i.e., campesterol and ß-sitosterol) and the hepatic mRNA levels of Scarb1 were significantly decreased. Water-soluble metabolite analysis showed that the muscular contents of several amino acids, including leucine, were significantly increased by C. gracilis feeding. The tendency toward an increase in the weight of the soleus muscle as a result of C. gracilis feeding may be due to the enhancement of muscle protein synthesis centered on leucine. Collectively, these results show that the oral administration of C. gracilis alleviates hepatic lipid accumulation in rats fed a high-sucrose and cholesterol-containing diet, indicating the potential use of C. gracilis as a food resource.

13.
Sci Rep ; 13(1): 3053, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810603

RESUMO

Suppressor of mek1 (Dictyostelium) homolog 2 (Smek2), was identified as one of the responsible genes for diet-induced hypercholesterolemia (DIHC) of exogenously hypercholesterolemic (ExHC) rats. A deletion mutation in Smek2 leads to DIHC via impaired glycolysis in the livers of ExHC rats. The intracellular role of Smek2 remains obscure. We used microarrays to investigate Smek2 functions with ExHC and ExHC.BN-Dihc2BN congenic rats that harbor a non-pathological Smek2 allele from Brown-Norway rats on an ExHC background. Microarray analysis revealed that Smek2 dysfunction leads to extremely low sarcosine dehydrogenase (Sardh) expression in the liver of ExHC rats. Sarcosine dehydrogenase demethylates sarcosine, a byproduct of homocysteine metabolism. The ExHC rats with dysfunctional Sardh developed hypersarcosinemia and homocysteinemia, a risk factor for atherosclerosis, with or without dietary cholesterol. The mRNA expression of Bhmt, a homocysteine metabolic enzyme and the hepatic content of betaine (trimethylglycine), a methyl donor for homocysteine methylation were low in ExHC rats. Results suggest that homocysteine metabolism rendered fragile by a shortage of betaine results in homocysteinemia, and that Smek2 dysfunction causes abnormalities in sarcosine and homocysteine metabolism.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Hipercolesterolemia , Hiper-Homocisteinemia , Fosfoproteínas Fosfatases , Sarcosina Desidrogenase , Animais , Ratos , Betaína/metabolismo , Glucose/metabolismo , Homocisteína/metabolismo , Hipercolesterolemia/genética , Hiper-Homocisteinemia/complicações , Fígado/metabolismo , Mutação , Ratos Endogâmicos BN , Sarcosina/metabolismo , Sarcosina Desidrogenase/deficiência , Erros Inatos do Metabolismo dos Aminoácidos/genética , Fosfoproteínas Fosfatases/genética
14.
J Oleo Sci ; 72(2): 189-197, 2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36631107

RESUMO

Perilla pomace, a by-product of oil extraction, is rich in nutrients, such as proteins, but it has not been used for purposes other than livestock feeding. The aim of this study was to determine how perilla pomace modulates glucose and lipid metabolism in Sprague-Dawley rats. Dried perilla pomace was added to diet at a concentration of 16%. One experimental group was administered perilla oil equivalent to that in the perilla pomace. After four weeks, the animals were euthanized, and biochemical parameters were measured. Two experiments were conducted using a low-fat (7% by weight) and a high-fat (21% by weight) diet. Regardless of the level of fat in the diets, no differences in food intake were found among the groups. In the low-fat diet-fed rats (Experiment 1), epididymal adipose tissue weight was slightly, but not significantly, lower in perilla pomace-fed rats than in those fed the control diet. Hepatic triglyceride and cholesterol levels were significantly reduced by perilla pomace compared to those in the control group. Serum lipid profiles (triglycerides and cholesterol) were similar to those in the liver, without statistically significant differences. Perilla pomace significantly diminished hepatic fatty acid synthase (FAS) activity. In high-fat diet-fed rats (Experiment 2), pomace did not significantly lower epididymal adipose tissue weight. Hepatic cholesterol levels were lower in rats on the perilla oil than in control rats. The activity of hepatic enzymes involved in fat oxidation was significantly higher in rats fed the perilla pomace than in those fed the control diet. Collectively, these results show that perilla pomace favorably modulates fat metabolism, and the specific effects depend on the fat content in the diet.


Assuntos
Metabolismo dos Lipídeos , Perilla , Animais , Ratos , Colesterol , Dieta Hiperlipídica , Gorduras na Dieta , Ácidos Graxos/análise , Fígado/metabolismo , Nutrientes , Ratos Sprague-Dawley , Triglicerídeos/análise
15.
J Nutr Sci Vitaminol (Tokyo) ; 69(5): 357-369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37940576

RESUMO

Nonalcoholic steatohepatitis (NASH) can progress to hepatic fibrosis, and is associated with cardiovascular and liver-related mortality. To understand the pathogenesis of NASH, reliable animal models of the disease are useful. In animal studies, the animals are usually fasted overnight before biospecimens are taken, but little is known about the effects of fasting. Here, we investigated the impact of overnight fasting for approximately 9 to 17 h on glucose and lipid metabolism in a Sprague-Dawley (SD) rat model of diet-induced moderate and advanced NASH in comparison to normal SD rats. Our results revealed that in the moderate NASH model rats, the fasting duration did not affect glucose and lipid metabolism, the histopathological findings, or the hepatic mRNA expression levels of genes related to lipid metabolism, cholesterol metabolism, inflammation, fibrosis, and oxidative stress. In contrast, in the normal rats, significant fasting time-dependent reductions were observed in the epididymal fat pad weight and the hepatic mRNA expression levels of adipose differentiation-related protein and heme oxygenase-1. Moreover, in the advanced NASH model rats, a significant fasting time-dependent reduction and increase were observed in the serum insulin level and mRNA expression level of alpha-smooth muscle actin, respectively. Our present results suggest that the influence of the overnight fasting duration differs among the healthy condition, moderate NASH, and advanced NASH statuses. Further studies are needed in humans to determine the appropriate overnight fasting duration for the accurate evaluation of glucose and lipid metabolism in NASH patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Ratos Sprague-Dawley , Glucose/metabolismo , Metabolismo dos Lipídeos , Dieta Hiperlipídica , Fígado/metabolismo , Cirrose Hepática/patologia , Jejum , RNA Mensageiro/metabolismo , Modelos Animais de Doenças
16.
Br J Nutr ; 107(5): 639-46, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21787451

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialised countries. Various mushrooms have been used in Eastern folk medicine for the treatment of lifestyle diseases. We previously found that the dietary intake of powdered whole Panellus serotinus (Mukitake) alleviates NAFLD in obese, diabetic db/db mice. In the present study, we investigated the influence of Mukitake fractional extracts on the development of NAFLD in db/db mice. A significant reduction in the hepatic TAG content, macrovesicular hepatocytes and activities of key enzymes for de novo synthesis of the fatty acid was observed in both the water-soluble Mukitake extract (WE) diet and the ethanol-soluble Mukitake extract (EE) diet groups compared with the control diet group of the db/db mice. The serum level of monocyte chemoattractant protein-1 (MCP-1), which is known to exacerbate insulin resistance, was significantly decreased in the WE group. On the other hand, the serum level of adiponectin, which plays a protective role against the metabolic syndrome, was significantly increased in the EE group. Additionally, differential analysis between Mukitake and Shiitake, mycelia from the same family, using liquid chromatography time-of-flight MS technology revealed that only seven and five compounds exist in WE and EE from Mukitake, respectively. In conclusion, the present study demonstrated that Mukitake displays at least two different physiological actions that alleviate NAFLD: one through the reduction in inflammatory damage by its suppression in MCP-1 production and the other through an increase in level of serum adiponectin and the prevention of visceral fat accumulation.


Assuntos
Agaricales/química , Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Fígado Gorduroso/prevenção & controle , Hipoglicemiantes/uso terapêutico , Medicina Tradicional do Leste Asiático , Obesidade/prevenção & controle , Adiponectina/sangue , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Fármacos Antiobesidade/química , Quimiocina CCL2/sangue , Quimiocina CCL2/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/complicações , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/química , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Mutantes , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Solubilidade , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
17.
Cardiovasc Drugs Ther ; 26(5): 427-31, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22798197

RESUMO

PURPOSE: Ezetimibe has been shown to inhibit dietary cholesterol absorption in animal models and humans, but studies on lymphatic lipid transport have not yet been performed. Rats subjected to permanent lymph duct cannulation were used to investigate the effects of ezetimibe on lipid transport. METHODS: Rats were fed diets with and without ezetimibe (5.0 mg/kg), and their lymph was collected after feeding to quantify lymphatic lipid levels. Total cholesterol content in the intestinal mucosa was also measured. RESULTS: Rats that consumed ezetimibe had significantly lower lymphatic total cholesterol transport with the reduction of esterified cholesterol transport. According to the calculation based on cholesterol consumption, ezetimibe reduced the total cholesterol lymphatic recovery rate by 54 %. We also determined that ezetimibe significantly reduced the total cholesterol content in the intestinal mucosa. CONCLUSION: This is the first direct evidence that ezetimibe inhibits esterified but not free cholesterol lymphatic transport in thoracic duct-cannulated rats. The results also indicate that ezetimibe is not involved in the lymphatic transport of triacylglycerols, phospholipids, or α-tocopherol.


Assuntos
Anticolesterolemiantes/farmacologia , Azetidinas/farmacologia , Colesterol/metabolismo , Linfa/metabolismo , Vasos Linfáticos/efeitos dos fármacos , Animais , Transporte Biológico/efeitos dos fármacos , Cateterismo , Esterificação , Ezetimiba , Vasos Linfáticos/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Ducto Torácico
18.
Biosci Biotechnol Biochem ; 76(3): 462-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22451385

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. The discovery of food components that would ameliorate NAFLD is therefore of interest. Lotus root, the edible rhizome of Nelumbo nucifera, contains a high level of polyphenolic compounds, and several health-promoting properties of lotus root have been reported. The present study examines whether dietary lotus root powder can protect db/db mice from hepatic injury. After 3 weeks of feeding, the hepatomegaly, hepatic triglyceride accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in the Lotus diet-fed db/db mice relative to the control mice. These effects were partly attributable to suppression of the lipogenic enzyme activities and mRNA expression by the Lotus diet. The serum levels of adiponectin, which has been reported to have a protective effect against NAFLD, were significantly higher in the Lotus group than in the Control group of the db/db mice. Moreover, the hepatic expression of such inflammatory genes as tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were markedly suppressed by the Lotus diet. We speculate that the development and progression of NAFLD were prevented by suppressing the expression of lipogenic and inflammatory genes as a result of the higher serum adioponectin level in the Lotus diet-fed db/db mice.


Assuntos
Complicações do Diabetes/prevenção & controle , Fígado Gorduroso/prevenção & controle , Nelumbo/química , Obesidade/complicações , Extratos Vegetais/farmacologia , Rizoma/química , Adiponectina/sangue , Animais , Biomarcadores/metabolismo , Complicações do Diabetes/metabolismo , Complicações do Diabetes/patologia , Suplementos Nutricionais , Fígado Gorduroso/complicações , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/lesões , Fígado/metabolismo , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica , Pós
19.
Lipids Health Dis ; 11: 52, 2012 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-22584034

RESUMO

BACKGROUND: Serum ß-cryptoxanthin levels are lower in overweight subjects than in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects have been reported. There are several reports that serum ß-cryptoxanthin levels in them were relatively lower than normal subjects. OBJECTIVE: We hypothesize that supplementation of highly concentrated ß-cryptoxanthin improves serum adipocytokine profiles in obese subjects. This study tested the association between ß-cryptoxanthin intake and serum adipocytokine levels. METHODS: An intervention study consisted of a 3-week long before-and-after controlled trial, where ß-cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women. RESULTS: The results indicated no significant changes in body weight or body mass index (BMI). Serum ß-cryptoxanthin levels increased significantly by 4-fold. Serum high molecular weight (HMW)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (PAI)-1 levels decreased. CONCLUSIONS: We concluded that increasing the intake of ß-cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.


Assuntos
Adipocinas/sangue , Bebidas , Citrus , Suplementos Nutricionais , Obesidade/tratamento farmacológico , Xantofilas/administração & dosagem , Administração Oral , Criptoxantinas , Feminino , Humanos , Japão , Lipídeos/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Pós-Menopausa
20.
Metabolites ; 12(1)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35050186

RESUMO

Choline, betaine, and L-carnitine are transformed into trimethylamine (TMA) by gut microbiota, absorbed into the liver, and oxidized into trimethylamine-N-oxide (TMAO) by flavin-containing monooxygenases. Elevated TMAO levels may negatively affect human health. As phosphatidylcholine (PC) is the main source of dietary choline, its intake or PC-rich foods may be harmful to human health; however, quantitative comparative information among dietary choline compounds (PC, glycerophosphocholine [GPC], and choline chloride [CC]) regarding in vivo generation of TMAO is lacking. Here, we compared the effects of PC, GPC, and CC on plasma TMAO levels in rats. Furthermore, we investigated their effects on gut microbiota at the genus level. Dietary PC did not affect plasma TMAO levels, whereas dietary GPC and CC significantly increased them. At the genus level, plasma TMAO levels were significantly negatively correlated with relative abundances of Anaerotruncus, Actinomyces, Enterococcus, Dialister, Clostridium XIVa, and Granulicatella; they were significantly positively correlated with that of Coprobacter. Moreover, the relative abundances of Anaerotruncus and Coprobacter were found to predict plasma TMAO levels. Therefore, dietary PC, unlike GPC or CC, does not increase plasma TMAO levels in rats. Furthermore, several gut microbes are associated with changes in plasma TMAO levels in rats fed with choline compounds.

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