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1.
Artigo em Inglês | MEDLINE | ID: mdl-27123033

RESUMO

The purpose of the present study was to examine the influence of a traditional yoga practice approach (morning daily practice, TY) compared to that of a Western yoga practice approach (once-twice weekly, evening practice, WY) on determinants of emotional well-being. To that end, in a pre/posttest between-subject design, measures of positive (PA) and negative affect (NA), mindfulness, perceived stress, and arousal states were taken in 24 healthy participants (20 women; mean age: 30.5, SD = 8.1 years) with an already existing WY practice, who either maintained WY or underwent a 2-week, five-times-per-week morning practice (TY). While WY participants maintained baseline values for all measures taken, TY participants showed significant beneficial changes for PA, NA, and mindfulness and a trend for improved ability to cope with stress at the completion of the intervention. Furthermore, TY participants displayed decreased subjective energy and energetic arousal. Altogether, findings indicate that the 2-week TY is beneficial over WY for improving perceived emotional well-being. The present findings (1) undermine and inspire a careful consideration and utilization of yoga practice approach to elicit the best benefits for emotional well-being and (2) support yoga as an evidence-based practice among healthy yoga practitioners.

2.
Atherosclerosis ; 228(1): 117-23, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23497783

RESUMO

AIMS: Bile acid sequestrants (BAS) and physical activity (RUN) decrease incidence of cardiovascular events. Both treatments are often prescribed, yet it is not known whether their beneficial effects are additive. We assessed the effects of BAS treatment alone and in combination with RUN on cholesterol metabolism, heart function and atherosclerotic lesion size in hypercholesterolemic mice. METHODS: Male Ldlr-deficient mice remained either sedentary (CONTROL), were treated with Colesevelam HCl (BAS), had access to a running wheel (RUN), or were exposed to BAS and RUN (BAS RUN). All groups were fed a high cholesterol diet for 12 weeks. Then, feces, bile and plasma were collected. Atherosclerotic lesion size was determined in the aortic arch and heart function by echocardiography. RESULTS: BAS RUN ran more than RUN (6.4 ± 1.4 vs. 3.5 ± 1.0 km/day, p < 0.05). BAS and BAS RUN displayed ~3-fold reductions in plasma cholesterol levels (p < 0.001), ~2.5-fold increases in fecal neutral sterol (p < 0.001) and bile acid (p = 0.01) outputs, decreases in biliary secretions of cholesterol (~6-fold, p < 0.0001) and bile acids (~2-fold, p < 0.001) vs. CONTROL while no significant effects were observed in RUN. Compared to CONTROL, lesion size decreased by 78% in both BAS and BAS RUN, (p < 0.0001). CONCLUSION: BAS reduce atherosclerosis in Ldlr-deficient mice, coinciding with a switch from body cholesterol accumulation to cholesterol loss. RUN slightly modulated atherosclerotic lesion formation but the combination of BAS and RUN had no clear additive effects in this respect.


Assuntos
Alilamina/análogos & derivados , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , Ácidos e Sais Biliares/metabolismo , Hipercolesterolemia , Condicionamento Físico Animal/fisiologia , Alilamina/farmacologia , Ração Animal , Animais , Anticolesterolemiantes/farmacologia , Aorta/diagnóstico por imagem , Aorta/metabolismo , Aterosclerose/diagnóstico por imagem , Débito Cardíaco/fisiologia , Colesterol/biossíntese , Colesterol/sangue , Cloridrato de Colesevelam , Ecocardiografia , Fezes , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/metabolismo , Hipercolesterolemia/fisiopatologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Receptores de LDL/genética , Receptores de LDL/metabolismo , Esteróis/metabolismo
3.
Int J Cardiol ; 169(6): 385-93, 2013 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-24383120

RESUMO

Diabetes and heart failure are very prevalent, and affect each other's incidence and severity. Novel therapies to reduce post-myocardial infarction (MI) remodeling that progresses into heart failure are urgently needed, especially in diabetic patients. Clinical studies have suggested that some oral anti-diabetic agents like metformin exert cardiovascular protective effects in heart failure patients with diabetes, whereas other agents may be deleterious. In the current review, we provide an overview of the cardio-specific effects of oral anti-diabetic drugs in animal models of acute MI, post-MI remodeling, and heart failure. Metformin has consistently been shown to ameliorate cardiac remodeling after ischemia/reperfusion (I/R) injury, as well as in several models of heart failure. Sulfonylurea derivatives are controversial with respect to their direct effects on the cardiovascular system. Thiazolidinediones protect against myocardial I/R injury, but their effects on post-MI remodeling are less clear and clinical studies raised concerns about their cardiovascular safety. Glucagon-like peptide-1 analogs have potential beneficial effects on the cardiovascular system that require further confirmation, whereas the results with dipeptidyl peptidase-4 inhibitors are equivocal. Current clinical guidelines, in the absence of prospective clinical trials that evaluated if certain oral anti-diabetic agents are superior over others, only provide generic recommendations, and do not take into account interesting experimental and mechanistic data. The available experimental evidence indicates that some anti-diabetic agents should be preferred over others if cardioprotective effects are warranted. These experimental clues need to be confirmed by clinical trials.


Assuntos
Modelos Animais de Doenças , Hipoglicemiantes/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Médicos , Pesquisa Translacional Biomédica , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardiologia/métodos , Humanos , Hipoglicemiantes/farmacologia , Isquemia Miocárdica/diagnóstico , Estudos Prospectivos , Pesquisa Translacional Biomédica/métodos , Resultado do Tratamento , Remodelação Ventricular/fisiologia
4.
Circ Heart Fail ; 6(1): 107-17, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23230309

RESUMO

BACKGROUND: Galectin-3 has been implicated in the development of organ fibrosis. It is unknown whether it is a relevant therapeutic target in cardiac remodeling and heart failure. METHODS AND RESULTS: Galectin-3 knock-out and wild-type mice were subjected to angiotensin II infusion (2.5 µg/kg for 14 days) or transverse aortic constriction for 28 days to provoke cardiac remodeling. The efficacy of the galectin-3 inhibitor N-acetyllactosamine was evaluated in TGR(mREN2)27 (REN2) rats and in wild-type mice with the aim of reversing established cardiac remodeling after transverse aortic constriction. In wild-type mice, angiotensin II and transverse aortic constriction perturbations caused left-ventricular (LV) hypertrophy, decreased fractional shortening, and increased LV end-diastolic pressure and fibrosis (P<0.05 versus control wild type). Galectin-3 knock-out mice also developed LV hypertrophy but without LV dysfunction and fibrosis (P=NS). In REN2 rats, pharmacological inhibition of galectin-3 attenuated LV dysfunction and fibrosis. To elucidate the beneficial effects of galectin-3 inhibition on myocardial fibrogenesis, cultured fibroblasts were treated with galectin-3 in the absence or presence of galectin-3 inhibitor. Inhibition of galectin-3 was associated with a downregulation in collagen production (collagen I and III), collagen processing, cleavage, cross-linking, and deposition. Similar results were observed in REN2 rats. Inhibition of galectin-3 also attenuated the progression of cardiac remodeling in a long-term transverse aortic constriction mouse model. CONCLUSIONS: Genetic disruption and pharmacological inhibition of galectin-3 attenuates cardiac fibrosis, LV dysfunction, and subsequent heart failure development. Drugs binding to galectin-3 may be potential therapeutic candidates for the prevention or reversal of heart failure with extensive fibrosis.


Assuntos
Amino Açúcares/uso terapêutico , DNA/genética , Galectina 3/genética , Expressão Gênica , Insuficiência Cardíaca/prevenção & controle , Miocárdio/patologia , Remodelação Ventricular , Animais , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Fibrose/genética , Fibrose/metabolismo , Fibrose/prevenção & controle , Galectina 3/antagonistas & inibidores , Galectina 3/biossíntese , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , Miocárdio/metabolismo , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
PLoS One ; 6(11): e24564, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22087215

RESUMO

AIMS/HYPOTHESIS: Bile acid sequestrants (BAS) reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet) Colesevelam HCl (BAS) for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13)C]-glucose, [2-(13)C]-glycerol, [1-(2)H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001), a ∼300% increased glucokinase flux (p = 0.001) and a ∼200% increased total hepatic glucose production rate (p = 0.0002). BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317) but not in liver (p = 0.189). Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030) and 3-fold in db/db mice (p = 0.002). CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.


Assuntos
Ácidos e Sais Biliares/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Animais , Ácidos e Sais Biliares/farmacologia , Glicemia/efeitos dos fármacos , Isótopos de Carbono/metabolismo , Isótopos de Carbono/farmacocinética , Carnitina/análogos & derivados , Carnitina/análise , Glucose/farmacocinética , Fígado/metabolismo , Taxa de Depuração Metabólica , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo
6.
Cardiovasc Diabetol ; 10: 85, 2011 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-21955567

RESUMO

BACKGROUND: Progressive remodeling after myocardial infarction (MI) is a leading cause of morbidity and mortality. Recently, glucagon-like peptide (GLP)-1 was shown to have cardioprotective effects, but treatment with GLP-1 is limited by its short half-life. It is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4), an enzyme which inhibits GLP-1 activity. We hypothesized that the DPP-4 inhibitor vildagliptin will increase levels of GLP-1 and may exert protective effects on cardiac function after MI. METHODS: Sprague-Dawley rats were either subjected to coronary ligation to induce MI and left ventricular (LV) remodeling, or sham operation. Parts of the rats with an MI were pre-treated for 2 days with the DPP-4 inhibitor vildagliptin (MI-Vildagliptin immediate, MI-VI, 15 mg/kg/day). The remainder of the rats was, three weeks after coronary artery ligation, subjected to treatment with DPP-4 inhibitor vildagliptin (MI-Vildagliptin Late, MI-VL) or control (MI). At 12 weeks, echocardiography and invasive hemodynamics were measured and molecular analysis and immunohistochemistry were performed. RESULTS: Vildagliptin inhibited the DPP-4 enzymatic activity by almost 70% and increased active GLP-1 levels by about 3-fold in plasma in both treated groups (p < 0.05 vs. non-treated groups). Cardiac function (ejection fraction) was decreased in all 3 MI groups compared with Sham group (p < 0.05); treatment with vildagliptin, either early or late, did not reverse cardiac remodeling. ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide) mRNA levels were significantly increased in all 3 MI groups, but no significant reductions were observed in both vildagliptin groups. Vildagliptin also did not change cardiomyocyte size or capillary density after MI. No effects were detected on glucose level and body weight in the post-MI remodeling model. CONCLUSION: Vildagliptin increases the active GLP-1 level via inhibition of DPP-4, but it has no substantial protective effects on cardiac function in this well established long-term post-MI cardiac remodeling model.


Assuntos
Adamantano/análogos & derivados , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Modelos Animais de Doenças , Insuficiência Cardíaca/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Nitrilas/administração & dosagem , Pirrolidinas/administração & dosagem , Adamantano/administração & dosagem , Animais , Dipeptidil Peptidase 4/metabolismo , Esquema de Medicação , Insuficiência Cardíaca/enzimologia , Masculino , Infarto do Miocárdio/enzimologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Vildagliptina
7.
Atherosclerosis ; 218(2): 323-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21802084

RESUMO

OBJECTIVE: Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in hypercholesterolemic mice. METHODS: Male LDLR-deficient mice (8 weeks old) had either access to a voluntary running wheel for 12 weeks (RUN) or remained sedentary (CONTROL). Both groups were fed a western-type/high cholesterol diet. Running activity and food intake were recorded. At 12 weeks of intervention, feces, bile and plasma were collected to determine fecal, biliary and plasma parameters of cholesterol metabolism and plasma cytokines. Atherosclerotic lesion size was determined in the aortic root. RESULTS: RUN weighed less (∼13%) while food consumption was increased by 17% (p=0.004). Plasma cholesterol levels were decreased by 12% (p=0.035) and plasma levels of pro-atherogenic lipoproteins decreased in RUN compared to control. Running modulated cholesterol catabolism by enhancing cholesterol turnover: RUN displayed an increased biliary bile acid secretion (68%, p=0.007) and increased fecal bile acid (93%, p=0.009) and neutral sterol (33%, p=0.002) outputs compared to control indicating that reverse cholesterol transport was increased in RUN. Importantly, aortic lesion size was decreased by ∼33% in RUN (p=0.033). CONCLUSION: Voluntary wheel running reduces atherosclerotic burden in hypercholesterolemic mice. An increased cholesterol turnover, specifically its conversion into bile acids, may underlie the beneficial effect of voluntary exercise in mice.


Assuntos
Aterosclerose/metabolismo , Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Hipercolesterolemia/metabolismo , Animais , Peso Corporal , Citocinas/sangue , Humanos , Masculino , Camundongos , Atividade Motora , Condicionamento Físico Animal , Receptores de LDL/genética , Risco , Corrida
8.
Nutr Metab (Lond) ; 7: 54, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20594315

RESUMO

Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT). After two weeks of voluntary wheel running (average 10.1 +/- 1.4 km/day) plasma triglycerides were lower (p < 0.05), while otherwise lipid and lipoprotein levels did not change. Macrophage cholesterol efflux towards plasma was significantly increased in running (n = 8) compared to sedentary (n = 6) mice (14.93 +/- 1.40 vs. 12.33 +/- 2.60%, p < 0.05). In addition, fecal excretion of bile acids (3.86 +/- 0.50 vs. 2.90 +/- 0.51 nmol/d, p = 0.001) and neutral sterols (2.75 +/- 0.43 vs. 1.94 +/- 0.22 nmol/d, p < 0.01) was significantly higher in running mice. However, RCT from macrophages to feces remained essentially unchanged in running mice compared with sedentary controls (bile acids: 3.2 +/- 1.0 vs. 2.9 +/- 1.1 % of injected dose, n.s.; neutral sterols: 1.4 +/- 0.7 vs. 1.1 +/- 0.5 % injected dose, n.s.). Judged by the plasma lathosterol to cholesterol ratio, endogenous cholesterol synthesis was increased in exercising mice (0.15 +/- 0.03 vs. 0.11 +/- 0.02, p < 0.05), while the hepatic mRNA expression of key transporters for biliary cholesterol (Abcg5/g8, Sr-bI) as well as bile acid (Abcb11) and phospholipd (Abcb4) excretion did not change. These data indicate that the beneficial effects of exercise on cardiovascular health include increased cholesterol efflux, but do not extend to other components of RCT. The increased fecal cholesterol excretion observed in running mice is likely explained by higher endogenous cholesterol synthesis, however, it does not reflect increased RCT in the face of unchanged expression of key transporters for biliary sterol secretion.

9.
Med Sci Sports Exerc ; 42(8): 1460-8, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20139791

RESUMO

PURPOSE: Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels, but the underlying mechanisms have not been fully explored. Exercise might provoke changes in cholesterol and bile acid metabolism and thereby reduce cardiovascular risk. We examined whether voluntary wheel running in mice modulates cholesterol and bile acid metabolism. METHODS: Male mice (10 wk old) were randomly assigned to have access to a voluntary running wheel for 2 wk (RUN group) or remained sedentary (SED group). Running wheel activity was recorded daily. In a first experiment, fecal sterol outputs, fecal bile acid profiles, plasma parameters, and expression levels of genes involved in cholesterol and bile acid metabolism were determined. In a second experiment, bile flow, biliary bile acid profile, and biliary secretion rates of cholesterol, phospholipids, and bile acids were determined. RESULTS: The RUN group ran an average of 10 km.d and displayed lower plasma cholesterol compared with SED (P = 0.030). Fecal bile acid loss was induced by approximately 30% in running mice compared with SED (P = 0.0012). A approximately 30% increase in fecal cholesterol output in RUN (P = 0.014) was consistent with changes in parameters of cholesterol absorption, such as reduced plasma plant sterol-cholesterol ratio (P = 0.044) and decreased jejunal expression of Npc1l1 (P = 0.013). Supportive of an increased cholesterol synthesis to compensate for fecal sterol loss were increased hepatic mRNA levels of HMGCoA reductase (P = 0.006) and an increased plasma lathosterol-cholesterol ratio (P = 0.0011) in RUN. CONCLUSIONS: Voluntary wheel running increased cholesterol turnover in healthy mice owing to an increased fecal bile acid excretion and a decreased intestinal cholesterol absorption. Enhanced cholesterol turnover may contribute to the established reduction of cardiovascular risk induced by regular exercise.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colesterol/metabolismo , Vesícula Biliar/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/sangue , Colesterol/sangue , Fezes/química , Hidroximetilglutaril-CoA Redutases/análise , Absorção Intestinal/fisiologia , Masculino , Camundongos , Fosfolipídeos/análise , Fosfolipídeos/metabolismo , Fitosteróis/sangue , Comportamento Sedentário , Esteróis/análise , Esteróis/metabolismo
10.
Hepatology ; 51(3): 806-16, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19998408

RESUMO

UNLABELLED: Diabetes is characterized by high blood glucose levels and dyslipidemia. Bile salt sequestration has been found to improve both plasma glycemic control and cholesterol profiles in diabetic patients. Yet bile salt sequestration is also known to affect triglyceride (TG) metabolism, possibly through signaling pathways involving farnesoid X receptor (FXR) and liver X receptor alpha (LXRalpha). We quantitatively assessed kinetic parameters of bile salt metabolism in lean C57Bl/6J and in obese, diabetic db/db mice upon bile salt sequestration using colesevelam HCl (2% wt/wt in diet) and related these to quantitative changes in hepatic lipid metabolism. As expected, bile salt sequestration reduced intestinal bile salt reabsorption. Importantly, bile salt pool size and biliary bile salt secretion remained unchanged upon sequestrant treatment due to compensation by de novo bile salt synthesis in both models. Nevertheless, lean and db/db mice showed increased, mainly periportally confined, hepatic TG contents, increased expression of lipogenic genes, and increased fractional contributions of newly synthesized fatty acids. Lipogenic gene expression was not induced in sequestrant-treated Fxr(-/-) and Lxralpha(-/-) mice compared with wild-type littermates, in line with reports indicating a regulatory role of FXR and LXRalpha in bile salt-mediated regulation of hepatic lipid metabolism. CONCLUSION: Bile salt sequestration by colesevelam induces the lipogenic pathway in an FXR- and LXRalpha-dependent manner without affecting the total pool size of bile salts in mice. We speculate that a shift from intestinal reabsorption to de novo synthesis as source of bile salts upon bile salt sequestration affects zonation of metabolic processes within the liver acinus.


Assuntos
Ácidos e Sais Biliares/metabolismo , Lipogênese , Fígado/metabolismo , Receptores Nucleares Órfãos/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Alilamina/análogos & derivados , Alilamina/farmacologia , Animais , Cloridrato de Colesevelam , Fígado/efeitos dos fármacos , Receptores X do Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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