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1.
Appl Physiol Nutr Metab ; 46(11): 1322-1330, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34038646

RESUMO

SESN2 and JNK are emerging powerful stress-inducible proteins in regulating lipid metabolism. The aim of this study was to determine the underlying mechanism of SESN2/JNK signaling in exercise to improve lipid disorder induced by high-fat diet (HFD). Our data showed that HFD and SESN2 knockout resulted in abnormalities including elevated body weight, increased fat mass, serum total cholesterol, lipid biosynthesis related proteins, and a concomitant increase of pJNK-Thr183/Tyr185. The above changes were reversed by exercise training. SESN2 silencing or JNK inhibition in palmitate-treated C2C12 further confirmed that SESN2 and JNK play a vital role in lipid biosynthesis. Rescue experiment further demonstrated that SESN2 reduced lipid biosynthesis through inhibition of JNK. SESN2/JNK signaling axis regulates lipid biosynthesis in both animal and cell models with abnormalities of lipid metabolism induced by HFD or palmitate treatment. This study provided evidence that exercise ameliorated lipid metabolic disorder induced by HFD feeding or by SESN2 knockout. SESN2 may improve lipid metabolism through inhibition JNK expression in skeletal muscle cells, providing a molecular mechanism that may represent an attractive target for the treatment of lipid disorder. Novelty: Exercise improved lipid disorder induced by HFD feeding and SESN2 knockout. SESN2 and JNK play a vital role in lipid biosynthesis in vivo and in vitro. SESN2 suppressed JNK to improve lipid metabolism in skeletal muscle cells.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Peroxidases/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Composição Corporal , Linhagem Celular , Transtornos do Metabolismo dos Lipídeos/etiologia , Lipídeos/biossíntese , Lipídeos/sangue , Fígado/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo
2.
FASEB J ; 34(5): 6198-6214, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32162746

RESUMO

Mitochondrial dysfunction is the leading cause of reactive oxygen species (ROS) burst and apoptosis in hepatic ischemia/reperfusion (I/R) injury. Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatotargeted agent that exerts hepatoprotective roles by regulating lipid metabolism. Our previous studies have shown that UDCA-LPE improves hepatic I/R injury by inhibiting apoptosis and inflammation. However, the role of UDCA-LPE in lipid metabolism and mitochondrial function in hepatic I/R remains unknown. In the present study, we investigated the role of UDCA-LPE in hepatic I/R by focusing on the interface of phospholipid metabolism and mitochondrial homeostasis. Livers from 28-week-old mice, primary hepatocytes and HepG2 cells were subjected to in vivo and in vitro I/R, respectively. Analyses of oxidative stress, imaging, ATP generation, genetics, and lipidomics showed that I/R was associated with mitochondrial dysfunction and a reduction in phospholipids. UDCA-LPE alleviated mitochondria-dependent oxidative stress and apoptosis and prevented the decrease of phospholipid levels. Our study found that cytosolic phospholipase A2 (cPLA2 ), a phospholipase that is activated during I/R, hydrolyzed mitochondrial membrane phospholipids and led to mitochondria-mediated oxidative stress and apoptosis. UDCA-LPE inhibited the interaction between cPLA2 and mitochondria and reduced phospholipid hydrolysis-mediated injury. UDCA-LPE might regulate the crosstalk between the phospholipid metabolism and the mitochondria, restore mitochondrial function and ameliorate I/R injury.


Assuntos
Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Hepatopatias/prevenção & controle , Lisofosfolipídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeos/metabolismo , Traumatismo por Reperfusão/complicações , Ácido Ursodesoxicólico/análogos & derivados , Animais , Apoptose , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Transtornos do Metabolismo dos Lipídeos/etiologia , Transtornos do Metabolismo dos Lipídeos/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio , Ácido Ursodesoxicólico/farmacologia
3.
Biochimie ; 169: 121-132, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786232

RESUMO

Vegetable lecithins, widely used in the food industry as emulsifiers, are a mixture of naturally occurring lipids containing more than 50% of phospholipids (PL). PL exert numerous important physiological effects. Their amphiphilic nature notably enables them to stabilise endogenous lipid droplets, conferring them an important role in lipoprotein transport, functionality and metabolism. In addition, beneficial effects of dietary lecithin on metabolic disorders have been reported since the 1990s. This review attempts to summarize the effects of various vegetable lecithins on lipid and lipoprotein metabolism, as well as their potential application in the treatment of dyslipidemia associated with metabolic disorders. Despite controversial data concerning the impact of vegetable lecithins on lipid digestion and intestinal absorption, the beneficial effect of lecithin supplementation on plasma and hepatic lipoprotein and cholesterol levels is unequivocal. This is especially true in hyperlipidemic patients. Furthermore, the immense compositional diversity of vegetable lecithins endows them with a vast range of biochemical and biological properties, which remain to be explored in detail. Data on the effects of vegetable lecithins alternative to soybean, both as supplements and as ingredients in different foods, is undoubtedly lacking. Given the exponential demand for vegetable products alternative to those of animal origin, it is of primordial importance that future research is undertaken in order to elucidate the mechanisms by which individual fatty acids and PL from various vegetable lecithins modulate lipid metabolism. The extent to which they may influence parameters associated with metabolic disorders, such as intestinal integrity, low-grade inflammation and gut microbiota must also be assessed.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Aditivos Alimentares/metabolismo , Lecitinas/metabolismo , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Suplementos Nutricionais/análise , Aditivos Alimentares/administração & dosagem , Aditivos Alimentares/química , Aditivos Alimentares/isolamento & purificação , Microbioma Gastrointestinal/fisiologia , Humanos , Absorção Intestinal/fisiologia , Lecitinas/administração & dosagem , Lecitinas/química , Lecitinas/isolamento & purificação , Gotículas Lipídicas/química , Gotículas Lipídicas/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Verduras/química
4.
Rev Invest Clin ; 71(3): 157-167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184331

RESUMO

Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenomics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associated with lipotoxicity.


Assuntos
Nutrigenômica , Obesidade/complicações , Proteínas de Soja/farmacologia , Animais , Humanos , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/prevenção & controle
5.
Rev. invest. clín ; 71(3): 157-167, May.-Jun. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1289683

RESUMO

Abstract Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenomics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associated with lipotoxicity.


Assuntos
Humanos , Animais , Proteínas de Soja/farmacologia , Nutrigenômica , Obesidade/complicações , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/prevenção & controle
6.
Am J Physiol Endocrinol Metab ; 313(6): E699-E709, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28851734

RESUMO

Cardiac intracellular lipid accumulation (steatosis) is a pathophysiological phenomenon observed in starvation and diabetes mellitus. Perilipin 2 (PLIN2) is a lipid droplet (LD)-associated protein expressed in nonadipose tissues, including the heart. To explore the pathophysiological function of myocardial PLIN2, we generated transgenic (Tg) mice by cardiac-specific overexpression of PLIN2. Tg hearts showed accumulation of numerous small LDs associated with mitochondrial chains and high cardiac triacylglycerol (TAG) content [8-fold greater than wild-type (WT) mice]. Despite massive steatosis, cardiac uptake of glucose, fatty acids and VLDL, systolic function, and expression of metabolic genes were comparable in the two genotypes, and no morphological changes were observed by electron microscopy in the Tg hearts. Twenty-four hours of fasting markedly reduced steatosis in Tg hearts, whereas WT mice showed accumulation of LDs. Although activity of adipose triglyceride lipase in heart homogenate was comparable between WT and Tg mice, activity of hormone-sensitive lipase (HSL) was 40-50% less in Tg than WT mice under both feeding and fasting conditions, suggesting interference of PLIN2 with HSL. Mice generated through crossing of PLIN2-Tg mice and HSL-Tg mice showed cardiac-specific HSL overexpression and complete lack of steatosis. The results suggest that cardiac PLIN2 plays an important pathophysiological role in the development of dynamic steatosis and that the latter was prevented by upregulation of intracellular lipases, including HSL.


Assuntos
Cardiopatias/genética , Transtornos do Metabolismo dos Lipídeos/genética , Miocárdio/metabolismo , Perilipina-2/genética , Esterol Esterase/genética , Animais , Feminino , Expressão Gênica/fisiologia , Terapia Genética/métodos , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/prevenção & controle , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/patologia , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Transgênicos , Miocárdio/patologia , Especificidade de Órgãos/genética , Perilipina-2/metabolismo , Esterol Esterase/fisiologia
7.
Diabetes Res Clin Pract ; 126: 248-253, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28288434

RESUMO

INTRODUCTION: Lipohypertrophy (LH) is one of the most common complications of insulin therapy. We conducted a prospective study in 18 UK centres to assess the impact of a targeted LH intervention on a range of clinical, biological and socio-economic parameters. METHODS: Seventy-five insulin-injecting patients were recruited randomly and were followed prospectively for 3-6months, with results compared to baseline values. Interventions included the use of an intensive education program and a switch to a 4mm pen needle. RESULTS: At all injection sites LH decreased significantly by the end of the study, either disappearing completely or shrinking by approximately 50% from its original diameter. Injections into LH decreased by more than 75% by the end. Most patients were not correctly rotating injection sites at the beginning but by the end most were, by a 5-fold margin. Only 1/3 of our subjects used the 4mm needle at the beginning of the study, however, virtually all did by study end. The mean HbA1c improved by more than 4mmol/L and there were significantly lower levels of unexpected hypoglycaemia and glucose variability. Total daily doses of insulin dropped by an average of 5.6 IU by study end. CONCLUSIONS: We believe the impressive clinical improvements seen with training to prevent LH can be achieved by wide adoption of the interventions outlined in this study.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/administração & dosagem , Insulina/efeitos adversos , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Educação de Pacientes como Assunto , Gordura Subcutânea/patologia , Adulto , Feminino , Humanos , Hipertrofia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autocuidado/métodos , Gordura Subcutânea/efeitos dos fármacos , Reino Unido
8.
J Neurosci ; 36(30): 8012-25, 2016 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-27466344

RESUMO

UNLABELLED: Aging and pathologic conditions cause intracellular aggregation of macromolecules and the dysfunction and degeneration of neurons, but the mechanisms are largely unknown. Prime examples are lysosomal storage disorders such as Niemann-Pick type C (NPC) disease, where defects in the endosomal-lysosomal protein NPC1 or NPC2 cause intracellular accumulation of unesterified cholesterol and other lipids leading to neurodegeneration and fatal neurovisceral symptoms. Here, we investigated the impact of NPC1 deficiency on rodent neurons using pharmacologic and genetic models of the disease. Improved ultrastructural detection of lipids and correlative light and electron microscopy identified lamellar inclusions as the subcellular site of cholesterol accumulation in neurons with impaired NPC1 activity. Immunogold labeling combined with transmission electron microscopy revealed the presence of CD63 on internal lamellae and of LAMP1 on the membrane surrounding the inclusions, indicating their origins from intraluminal vesicles of late endosomes and of a lysosomal compartment, respectively. Lamellar inclusions contained cell-intrinsic cholesterol and surface-labeled GM1, indicating the incorporation of plasma membrane components. Scanning electron microscopy revealed that the therapeutic drug candidate ß-cyclodextrin induces the subplasmalemmal location of lamellar inclusions and their subsequent release to the extracellular space. In parallel, ß-cyclodextrin mediated the NPC1-independent redistribution of cholesterol within neurons and thereby abolished a deleterious cycle of enhanced cholesterol synthesis and its intracellular accumulation, which was indicated by neuron-specific transcript analysis. Our study provides new mechanistic insight into the pathologic aggregation of macromolecules in neurons and suggests exocytosis as cellular target for its therapeutic reversal. SIGNIFICANCE STATEMENT: Many neurodegenerative diseases involve pathologic accumulation of molecules within neurons, but the subcellular location and the cellular impact are often unknown and therapeutic approaches lacking. We investigated these questions in the lysosomal storage disorder Niemann-Pick type C (NPC), where a defect in intracellular cholesterol transport causes loss of neurons and fatal neurovisceral symptoms. Here, we identify lamellar inclusions as the subcellular site of lipid accumulation in neurons, we uncover a vicious cycle of cholesterol synthesis and accretion, which may cause gradual neurodegeneration, and we reveal how ß-cyclodextrin, a potential therapeutic drug, reverts these changes. Our study provides new mechanistic insight in NPC disease and uncovers new targets for therapeutic approaches.


Assuntos
Corpos de Inclusão/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Metabolismo dos Lipídeos , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Neurônios/metabolismo , Proteínas/metabolismo , Animais , Células Cultivadas , Feminino , Peptídeos e Proteínas de Sinalização Intracelular , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/patologia , Proteína C1 de Niemann-Pick , Ratos , Células Ganglionares da Retina
9.
Med Tr Prom Ekol ; (12): 25-29, 2016.
Artigo em Inglês, Russo | MEDLINE | ID: mdl-30351727

RESUMO

The authors evaluated negative effects of cadmium and arsenic compounds on health of population residing near storage of extraction and processing waste of ore mining and processing enterprise. Hygienic analysis covered quality of ambient air, drinkable water and foods, evaluation of risk factors of lipid metabolism disorders. Clinical and laboratory examination involved 137 children and 99 adults in chronic multi-environmental (ambient air, water, foods) exposure to metals (cadmium and arsenic, HI 1.21-1.29), diagnosed endocrine diseases including lipid metabolism disorders (excessive nutrition and obesity, E67.8-66.0) in adults 1.4 times more, and in children in 1.7-2.2 times more than in the reference group. Direct probable statistically significant cause-effect relationship was established between lipid metabolism disorders and serum levels of cadmium and arsenic (R² = 0,36-0,95; 71,07≤ F ≤2597,94; p< 0,001). In multi-environmental exposure to cadmium and arsenic, reduced index of lipid metabolic disorders risk in adult population exceeds upper limit of low risk level (0,05) at 33 years of age, of high risk level (0,35) - at 58 years of age and very high (0,6) - at 63 years of age.


Assuntos
Arsênio/sangue , Cádmio/sangue , Exposição Ambiental , Transtornos do Metabolismo dos Lipídeos , Mineração , Adolescente , Adulto , Fatores Etários , Poluentes Atmosféricos/efeitos adversos , Criança , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Exposição Ambiental/prevenção & controle , Feminino , Contaminação de Alimentos/análise , Contaminação de Alimentos/prevenção & controle , Humanos , Transtornos do Metabolismo dos Lipídeos/diagnóstico , Transtornos do Metabolismo dos Lipídeos/epidemiologia , Transtornos do Metabolismo dos Lipídeos/etiologia , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Federação Russa/epidemiologia , Fatores de Tempo , Poluentes Químicos da Água/efeitos adversos
10.
Food Funct ; 6(3): 902-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25630053

RESUMO

The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-α in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes.


Assuntos
Angelica sinensis/química , Diabetes Mellitus Tipo 2/dietoterapia , Hipoglicemiantes/uso terapêutico , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Raízes de Plantas/química , Polissacarídeos/uso terapêutico , Estado Pré-Diabético/dietoterapia , Tecido Adiposo Branco/imunologia , Tecido Adiposo Branco/metabolismo , Tecido Adiposo Branco/patologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/uso terapêutico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Glicogênio/agonistas , Glicogênio/metabolismo , Hiperglicemia/prevenção & controle , Hiperinsulinismo/prevenção & controle , Hiperlipidemias/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/isolamento & purificação , Hipolipemiantes/administração & dosagem , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/uso terapêutico , Resistência à Insulina , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos Endogâmicos BALB C , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Pâncreas/imunologia , Pâncreas/metabolismo , Pâncreas/patologia , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificação , Estado Pré-Diabético/imunologia , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/patologia , Distribuição Aleatória
11.
Gene ; 554(2): 148-54, 2015 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-25445284

RESUMO

L-Carnitine supplementation has been used to reduce obesity caused by high-fat diet, which is beneficial for lowering blood and hepatic lipid levels, and for ameliorating fatty liver. However, whether l-carnitine may affect irregular feeding-induced obesity and lipid metabolism disorder is still largely unknown. In the present study, we developed a time-delayed pattern of eating, and investigated the effects of l-carnitine on the irregular eating induced adiposity in mice. After an experimental period of 8 weeks with l-carnitine supplementation, l-carnitine significantly inhibited body weight increase and epididymal fat weight gain induced by the time-delayed feeding. In addition, l-carnitine administration decreased levels of serum alanine aminotransferase (GPT), glutamic oxalacetic transaminase (GOT) and triglyceride (TG), which were significantly elevated by the irregular feeding. Moreover, mice supplemented with l-carnitine did not display glucose intolerance-associated hallmarks, which were found in the irregular feeding-induced obesity. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that l-carnitine counteracted the negative alterations of lipid metabolic gene expression (fatty acid synthase, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, cholesterol 7α-hydroxylase, carnitine/acylcarnitine translocase) in the liver and fat of mice caused by the irregular feeding. Therefore, our results suggest that the time-delayed pattern of eating can induce adiposity and lipid metabolic disorders, while l-carnitine supplementation might prevent these negative symptoms.


Assuntos
Carnitina/administração & dosagem , Comportamento Alimentar/fisiologia , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Obesidade/prevenção & controle , Gordura Abdominal/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fatores de Tempo
12.
Curr Med Chem ; 21(24): 2734-42, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24606523

RESUMO

Natural selection clearly favors the accumulation and storage of lipids in humans, predisposing women to store excess fat in gluteal regions and predisposing males to store excess fat in visceral regions. In addition, gender differences are reported with respect to the concentrations of circulating lipids and lipoproteins, with lower concentrations of total cholesterol and low density lipoprotein (LDL)-cholesterol in premenopausal women than in men. This latter evidence renders gender differences in fat distribution and whole-body lipid metabolism of particular interest with respect to the incidence and prevalence of human diseases. Although the mechanisms underlying gender-related differences in body fat distribution and lipid homeostasis remain to be fully determined, the reported differences appear to principally reflect the actions of the sex steroid hormone estrogen on whole-body lipid metabolism. In the present review, we dissect the role played by 17ß-estradiol, the most active between estrogens, and by its receptors in regulating lipid homeostasis in adipose tissue, liver, and brain, evaluating the potential impact of this hormone in preventing lipid abnormalities.


Assuntos
Estradiol/metabolismo , Estrogênios/metabolismo , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Caracteres Sexuais , Estradiol/farmacologia , Estrogênios/farmacologia , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Transtornos do Metabolismo dos Lipídeos/metabolismo , Masculino
13.
Sci Rep ; 3: 2749, 2013 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-24067358

RESUMO

We investigated the effects of extracts of Benifuuki (a tea cultivar that contains methylated catechins such as epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me)) in mice fed a high-fat/high-sucrose (HF/HS) diet. This tea cultivar was then compared with an extract of Yabukita (a popular tea cultivar that lacks methylated catechins). For 6 weeks, C57BL/6J mice were fed either HF/HS diet with or without tea extracts from tea cultivars, which contained almost identical ingredients except for methylated catechins (i.e., Yabukita (0.2% and 1%) or Benifuuki (0.2% and 1%) extract powders). Supplementation with Benifuuki 0.2% markedly lowered plasma levels of TG and NEFAs compared with mice supplemented with Yabukita 0.2%. The diet containing Benifuuki 1% decreased adipose tissue weights, liver TG, and expression of lipogenic genes in the liver. These results suggested that Benifuuki had much greater lipid-lowering effects than Yabukita. Taken together, these data suggest that methylated catechins direct the strong lipid-lowering activity of Benifuuki.


Assuntos
Catequina/uso terapêutico , Transtornos do Metabolismo dos Lipídeos/tratamento farmacológico , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Extratos Vegetais/uso terapêutico , Chá/química , Absorção , Tecido Adiposo/efeitos dos fármacos , Animais , Catequina/farmacologia , Colesterol/metabolismo , Dieta Hiperlipídica , Sacarose Alimentar , Ácidos Graxos não Esterificados/sangue , Comportamento Alimentar/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Transtornos do Metabolismo dos Lipídeos/sangue , Transtornos do Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , Fitoterapia , Extratos Vegetais/farmacologia , Triglicerídeos/sangue
14.
Neurol Res ; 35(1): 59-64, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23317800

RESUMO

OBJECTIVE: The present study was undertaken to evaluate whether resveratrol (RSV) modulates membrane lipid composition, as well as on ganglioside profile in ischemia/reperfusion injury. METHODS: Global cerebral ischemia was induced by four-vessel occlusion for 10 minutes. RSV (30 mg/kg) or vehicle was intraperitoneally administered to rats 7 days prior to ischemia. Brain structures were homogenized with chloroform/methanol for ganglioside, phospholipids, and cholesterol levels. RESULTS: RSV significantly prevented the reduction in the total content of gangliosides, phospholipids, and cholesterol in hippocampi and cerebral cortex induced by global cerebral ischemia. Although ischemia/reperfusion decreased ganglioside content, the ganglioside profiles were apparently not modified. CONCLUSIONS: Our experiments suggest that lipid metabolism is important for development of ischemic damage and indicate that RSV treatment 7 days prior to ischemia may prevent membrane lipid loss.


Assuntos
Antioxidantes/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Transtornos do Metabolismo dos Lipídeos/etiologia , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Estilbenos/uso terapêutico , Animais , Colesterol/metabolismo , Cromatografia em Camada Fina , Modelos Animais de Doenças , Gangliosidoses/metabolismo , Masculino , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar , Resveratrol
15.
J Endocrinol ; 214(3): 267-76, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22700193

RESUMO

It has been hypothesized that deviations in glucocorticoid secretion and/or action may contribute to somatic and biochemical changes observed in patients with and animal models of insulin resistance (IR). In this study, we analyzed changes in rat adrenocortical function and morphology associated with the development of IR, generated in male adult rats by the addition of 30% sucrose to the drinking water. Caloric intake, body and adipose tissue weights, and biochemical parameters associated with IR were determined. Expression levels of Star, Cyp11A1, Mc2r, Pparγ (Pparg), and Cd36 were evaluated by real-time PCR, histochemical analysis of the adrenal cortex was performed using Masson's trichrome and Sudan III staining, and corticosterone levels were measured by RIA. After 7 weeks of sucrose administration, higher serum glucose, insulin, and triglyceride levels and an altered glycemic response to an i.p. insulin test were detected. Adrenal glands showed a neutral lipid infiltration. An increase in Star, Cyp11A1, Mc2r, Pparg and Cd36 and a decrease in Mc2r levels were also found. Furthermore, sucrose-treated animals exhibited higher basal corticosterone levels and a blunted response to ACTH injection. Noteworthy, the adrenocortical (functional and histological) abnormalities were prevented in sucrose-treated rats by the simultaneous administration of an insulin-sensitizing PPARγ agonist. In conclusion, sucrose-induced IR affects adrenocortical morphology and function possibly via the generation of adipokines or lipid metabolites within the adrenal gland. These abnormalities are prevented by the administration of a PPARγ agonist by mechanisms involving both extra- and intra-adrenal effects.


Assuntos
Córtex Suprarrenal/metabolismo , Sacarose Alimentar/farmacologia , Resistência à Insulina/fisiologia , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , PPAR gama/agonistas , Tiazolidinedionas/farmacologia , Córtex Suprarrenal/patologia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Corticosterona/sangue , Ingestão de Energia/efeitos dos fármacos , Ingestão de Energia/fisiologia , Hormônios/farmacologia , Hipoglicemiantes/farmacologia , Insulina/sangue , Insulina/farmacologia , Transtornos do Metabolismo dos Lipídeos/metabolismo , Transtornos do Metabolismo dos Lipídeos/patologia , Masculino , PPAR gama/metabolismo , Ratos , Ratos Wistar , Rosiglitazona , Triglicerídeos/sangue
16.
Br J Gen Pract ; 61(583): e81-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21276328

RESUMO

BACKGROUND: Laboratory testing has increased dramatically over recent decades, which is a consequence particularly of repeat testing or monitoring, as either a response to treatment or follow-up. AIM: To assess rates of measurement of lipid levels (total cholesterol, high-density lipoprotein, triglyceride) for diagnosis and monitoring over the last 20 years. DESIGN OF STUDY: Audit of electronic database. SETTING: A single region in the UK (Oxfordshire). METHOD: Specimens from individual patients were matched over time. All tests that were the third or more in a 3-year period were considered to be for monitoring, while the first and second were considered to be for diagnosis. As recent evidence-based recommendations suggest that frequent monitoring of cholesterol may reflect measurement error rather than true changes, between one and three tests in each 3-year period were considered to be 'necessary'. RESULTS: Over the 20 years from 1987 there has been a more than 15-fold rise in the overall number of lipid tests requested. After a small decline in the early 1990s, testing rose steadily after publication of several large statin trials, particularly tests requested in primary rather than secondary care. Repeat testing (likely to be for monitoring) rose from 24% of tests (1993-1995) to 61% (2005-2007), with between 42% and 79% of tests in 2005-2007 possibly being unnecessary. Mean cholesterol values declined over time from 1996 onwards. CONCLUSION: In the last decade, the number of cholesterol tests performed in Oxfordshire has risen dramatically. Much of this appears to be for monitoring purposes rather than case finding or risk assessment. The majority of cholesterol tests requested may be unnecessary.


Assuntos
Testes Diagnósticos de Rotina/estatística & dados numéricos , Transtornos do Metabolismo dos Lipídeos/diagnóstico , Lipídeos/sangue , Procedimentos Desnecessários/estatística & dados numéricos , Adolescente , Adulto , Idoso , Testes Diagnósticos de Rotina/tendências , Inglaterra , Métodos Epidemiológicos , Feminino , Humanos , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Masculino , Pessoa de Meia-Idade , Procedimentos Desnecessários/tendências , Adulto Jovem
17.
Med Tr Prom Ekol ; (12): 38-44, 2010.
Artigo em Russo | MEDLINE | ID: mdl-21446066

RESUMO

The authors demonstrated use of water-alcohol extracts of green and black tea for possible prevention of carbohydrates and lipid metabolism disorders in rats liver due to acetone intoxication. Polyphenols obtained from tea and injected into the animals before acetone intoxication resulted in preserved serum glucose level, phospholipid and neutral lipid contents, lower levels of cholesterol, triacylglycerines, saturated fatty acids in liver.


Assuntos
Acetona/toxicidade , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Chá/química , Animais , Glicemia/efeitos dos fármacos , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/prevenção & controle , Fígado/patologia , Masculino , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fosfolipídeos/metabolismo , Polifenóis , Ratos , Ratos Wistar
19.
J Am Acad Child Adolesc Psychiatry ; 46(6): 687-700, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17513981

RESUMO

OBJECTIVE: To review weight and metabolic effects of mood-stabilizing treatments in pediatric bipolar disorder. METHOD: Systematic PubMed/Medline search of studies reporting on change in weight and/or glucose/lipid values with mood-stabilizing drugs in at least nine pediatric patients with bipolar disorder. RESULTS: Nineteen studies, including 24 medication trials in 684 patients (mean age, 12.3 +/- 2.9 years) were included. Youngsters received lithium, antiepileptics, or their combinations (n = 459), or second-generation antipsychotics, alone or combined with lithium or divalproex (n = 225), for 4 to 48 (mean, 15.4 +/- 12.7) weeks. Weight increase was significant/clinically relevant in 18 (75.0%) trials. Weight loss was significant with topiramate (2 studies, 38 subjects) and present with aripiprazole (1 study, 14 subjects). In trials lasting < or =12 weeks, weight gain was greater with second-generation antipsychotics plus mood stabilizers (5.5 +/- 1.8 kg) compared to mood-stabilizer monotherapy (1.2 +/- 1.9 kg, p <.05, Cohen's d = 2.33) or mood-stabilizer cotreatment (2.1 +/- 1.3 kg, p <.05, Cohen's d = 2.17), but not compared to antipsychotic monotherapy (3.4 +/- 1.3 kg, p >.05, Cohen's d = 1.34). Nonfasting glucose/lipid changes were nonsignificant in two second-generation antipsychotic trials (n = 61, 8.9%). CONCLUSIONS: Data are sparse regarding body composition effects and lacking for fasting metabolic effects of mood stabilizers in pediatric bipolar disorder. Combining antipsychotics with mood stabilizers seems to lead to greater weight gain than treatment with one or two mood stabilizers.


Assuntos
Anticonvulsivantes/efeitos adversos , Antimaníacos/efeitos adversos , Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Transtornos do Metabolismo de Glucose/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Compostos de Lítio/efeitos adversos , Aumento de Peso , Adolescente , Criança , Quimioterapia Combinada , Transtornos do Metabolismo de Glucose/prevenção & controle , Humanos , Transtornos do Metabolismo dos Lipídeos/prevenção & controle
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