Aerobic training induces differential expression of genes involved in lipid metabolism in skeletal muscle and white adipose tissues.

Aerobic training induces adaptive responses in skeletal muscles and white adipose tissues, thus facilitating lipid utilization as energy substrates during a physical exercise session. However, the effects of training on cytokines levels and on transcription factors involved in lipid metabolism in muscle and different white adipose depots are still unclear; therefore, these were the aims of the present study. Nineteen adult male Wistar rats were randomly assigned to a trained group or a control, non-trained group. The 10-week training protocol consisted of running on a treadmill, during 1 hour per day, 5 days per week, at 75% of maximum aerobic speed. As expected, trained rats improved their aerobic performance and had augmented citrate synthase activity in the soleus, while the control rats did not. Although body weight was not different between groups, the adiposity index and white adipose depots (ie, epididymal and retroperitoneal) were reduced in trained rats. Training reduced serum concentration of insulin, but failed to change serum concentrations of glucose, triacylglycerol, total cholesterol, and nonesterified fatty acids. Training increased sterol regulatory element-binding protein-1c expression in the gastrocnemius and epididymal adipose tissue, and reduced peroxisome proliferator-activated receptor γ (PPARγ) expression in most of the tissues analyzed. The expression of PPARα and carnitine palmitoyltransferase 1 increased in the gastrocnemius and mesenteric adipose tissue but reduced in epididymal adipose tissue. Triacylglycerol content and tribbles 3 expression reduced in the gastrocnemius of trained rats. Tumor necrosis factor-α and interleukin-6 were increased in all adipose depots evaluated. Collectively, our data indicate that the 10-week aerobic training changed gene expression to improve muscle oxidative metabolism and facilitate lipid degradation in adipose tissues. Our data also highlight the existence of adaptive responses that are distinct between the skeletal muscle and white adipose tissue and between different adipose depots.

Increase in liver cytosolic lipases activities and VLDL-TAG secretion rate do not prevent the non-alcoholic fatty liver disease in cafeteria diet-fed rats.

We have previously shown that the cafeteria diet increases body fat mass, plasma triacylglycerol (TAG) and insulin levels, glucose uptake by white and brown adipose tissues, as well as the sympathetic activity to both adipose tissues in Wistar rats. The metabolic pathways responsible for the development of non-alcoholic fatty liver disease (NAFLD) were examined in cafeteria diet-fed rats. After 3 weeks offering cafeteria diet, we evaluated: (i) activity of the sympathetic nervous system by norepinephrine turnover rates; (ii) de novo fatty acid synthesis in vivo using 3H2O; (iii) secretion of very low density lipoprotein (VLDL)-TAG secretion measuring serum TAG levels after administration of lipase lipoprotein inhibitor, (iv) liver cytosolic lipases activities and (v) liver mRNA expression of enzymes involved in lipids secretion and oxidation by RT-PCR. The cafeteria diet induced an increase in TAG (120%) and cholesterol (30%) liver contents. Cafeteria diet did not change the sympathetic nervous system activity to liver, but induced a marked increase in the lipogenesis (approximately four-fold) and significant increase in cytosolic lipases activities (46%) and VLDL-TAG secretion (22%) compared to control diet-fed rats. The cafeteria diet also increased the microsomal triglyceride transfer protein (30%) and carnitine palmitoyltransferase I (130%) mRNA expression but decreased the apolipoprotein B100 (26%) mRNA expression. Our findings demonstrate that the increase in the cytosolic lipases activities and VLDL-TAG secretion rates were not able to compensate for the increased lipogenesis rates induced by the cafeteria diet, resulting in NAFLD.

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets.

Long-term effects of angiotensin-(1-7) on lipid metabolism in the adipose tissue and liver.

The angiotensin (Ang) converting enzyme 2/Ang-(1-7)/Mas axis has been described to have a beneficial role on metabolic disorders. In the present study, the use of a transgenic rat model that chronically overexpresses Ang-(1-7) enabled us to investigate the chronic effects of this peptide on lipid accumulation in the liver and adipose tissue. The transgenic group showed a marked tendency toward increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and decreased lipoprotein lipase (LPL) expression and activity in epididymal adipose tissue. We also showed that Mas receptor-knockout mice had decreased PPARγ expression in adipose tissue, accompanied by an increase in LPL activity. These results confirm the regulation of adipose tissue LPL activity by Ang-(1-7) and suggest that this occurs independent of PPARγ expression. The reduced adiposity index of transgenic rats, due to the effect of Ang-(1-7), was accompanied by a decrease in lipogenesis. These findings suggest a direct effect of Ang-(1-7) on lipogenesis, independent of the stimulatory effect of insulin. Furthermore, the decreased concentration of triacylglycerol in the liver of transgenic rats may result from increased activity of cytosolic lipases and decreased fatty acid uptake from the adipose tissue, determined from fatty acid-binding protein expression, and hepatic de novo fatty acid synthesis, evaluated by fatty acid synthase expression. The data clearly show that Ang-(1-7) regulates lipid metabolism in the adipose tissue and liver.

Differential modulation of cytosolic lipases activities in liver and adipose tissue by high-carbohydrate diets.

Several studies have demonstrated that a high-fructose (FRUC) diet induces metabolic and haemodynamic abnormalities, known as the metabolic syndrome, which are characterised by obesity, glucose intolerance, insulin resistance, dyslipidaemia and hypertension. In this study, the effect of a FRUC diet (60 % fructose) for 8 weeks on the metabolism of lipids in liver and epididymal adipose tissue from Wistar rats was compared with the AIN-93M diet and the effects of the AIN-93M diet were compared with a chow diet. The FRUC diet induced marked increases in both hepatocyte lipid droplet volume and postprandial serum levels of triacylglycerol (TAG), but reduced the postprandial serum levels of insulin. The AIN-93M diet induced marked increases in the hepatocyte lipid droplet volume and the serum levels of insulin, without affecting the serum levels of TAG. We found that isocaloric substitution of cornstarch, dextrinised cornstarch and sucrose (AIN-93M diet) for fructose did not affect the hepatic VLDL-TAG secretion and adipose tissue glucose uptake, lipolysis and cytosolic lipases activities in rats. However, the high-fructose diet induced a severe steatosis in liver accompanied by a decrease in cytosolic lipases activities. In adipose tissue, the FRUC diet induced a decrease in the lipoprotein lipase activity, and an increase in lipogenesis. FRUC and AIN-93M diets induced changes in lipid homeostasis in liver and adipose tissue by distinct biochemical mechanisms.

Distinct metabolic pathways trigger adipocyte fat accumulation induced by high-carbohydrate and high-fat diets.

OBJECTIVE: Several metabolic pathways may be associated with obesity development and may be differentially modulated by dietary constituents. The aim of this study was to access the adipocyte metabolic pathways that lead to lipid accumulation in fat cells of mice fed a high-carbohydrate or high-fat diet. METHODS: Male Swiss mice ages 7 to 8 wk were fed a standard laboratory rodent diet-chow diet, a high-carbohydrate (HC) diet, or a high-fat (HF) diet for 8 wk. RESULTS: Animals fed the HC diet exhibited a high lipogenesis rate and lipoprotein lipase activity even in a fasted state. Peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding proteins-1 mRNAs were increased in adipose tissue. The HF diet did not promote the lipogenic pathways but attenuated lipolytic activity and glucose uptake in adipocytes. CONCLUSION: The HC diet induces constitutive expression of lipogenic transcription factors during fasting, whereas the HF diet decreases lipolysis in adipocytes. Both pathways may contribute to increase fat stores and maintain an obese state.

Evaluation of calcium supplementation with algae (Lithothamnion muelleri) on metabolic and inflammatory parameters in mice fed a high refined carbohydrate-containing diet.

The aim of the present study was to evaluate the potential of calcium supplementation from Lithothamnium muelleri algae on metabolic and inflammatory parameters in mice with increased adiposity. Male mice were fed and divided during 8 weeks in: control (C), a high refined carbohydrate-containing diet (HC), HC diet supplemented with 1% of Lithothamnion muelleri algae (HC + A) and HC diet supplemented with 0.9% calcium carbonate (HC + C). Animals fed HC diet had increased body weight gain and adiposity, serum glucose and cholesterol, glucose intolerance and decreased insulin sensitivity, compared to control diet. However, the HC + A and HC + C groups did not prevent these aspects and were not able to change the CD14 + cells population in adipose tissue of animals fed HC diet. Calcium supplementation with Lithothamnium muelleri algae and calcium carbonate had no protective effect against the development of adiposity, metabolic and inflammatory alterations induced by HC diet.

Increased expression of oxidative enzymes in adipose tissue following PPARα-activation.

OBJECTIVE: Evaluate the effect of fenofibrate treatment on the expression of PPARα and oxidative enzymes in adipose tissue. MATERIALS/METHODS: Wistar male rats were fed a balanced diet supplemented with 100mg.Kg-1 bw.day-1 fenofibrate (Sigma) during nine days. Plasma glucose, free fatty acids (FFA) leptin and insulin were determined. PPARα, ACO and CPT-1 mRNA expression and amount of PPARα and PPARγ protein were assessed in epididymal adipose tissue. Oral glucose tolerance test was evaluated into overnight fasted rats. Glucose uptake was measured in adipocytes isolated from epididymal fat pads in the presence or absence of insulin (25ng/mL). RESULTS: Fenofibrate treatment increased PPARα and PPARγ protein abundance in adipose tissue. In addition to it well- known effect on oxidative enzymes in liver, fenofibrate treatment also induces a high expression of Acyl CoA Oxidase (ACO) and Carnitine palmitoyltransferase 1 (CPT-1) in adipose tissue. Furthermore, we have shown that the fenofibrate treatment improves the glucose tolerance and enhance the glucose uptake by adipocytes. CONCLUSION: Altogether, the data suggest that fenofibrate have a direct effect in adipose tissue contributing to the low adiposity and improvement of glucose homeostasis.

Adiposidade e perfil metabólico em crianças de escolas da zona urbana de Ouro Preto-MG / Adiposity and metabolic profile of schoolchildren in the urban areas of Ouro Preto, Minas Gerais

A obesidade, doença multifatorial definida como excesso de gordura corporal, apresenta concomitância entre fatores de risco genéticos e ambientais. O diagnóstico precoce e as intervenções no período crítico do desenvolvimento da obesidade - infância e adolescência - têm sido recomendados, buscando-se evitar desfechos desfavoráveis na idade adulta. Este estudo transversal teve como objetivo caracterizar perfil lipídico, glicemia, adiponectina, leptina e grelina de escolares entre seis e nove anos, portadores de sobrepeso e obesidade, do município de Ouro Preto-MG. Os dados foram analisados a partir do teste de normalidade Shapiro Wilk; e nas comparações entre os grupos foi aplicado o teste paramétrico (Teste t) ou não paramétrico (Teste Mann Whitney), adotando-se intervalo de confiança de 95% e nível de significância para valores ≤ 0,05. A idade média da população escolar foi de 7,8 ± 1,1 anos, com prevalência de 8,9% de sobrepeso e 3% de obesidade. Foram identificados hipercolesterolemia em 5,5%, HDL alterado em 98,7%, taxa limítrofe de LDL em 32,4% e glicemia alterada em 46,6% das crianças. Na análise estratificada quanto ao gênero, foram observados valores maisaltos para leptina em meninas (p=0,032) e grelina nos meninos (p=0,033), não havendo diferença para as demais variáveis. Os resultados demonstram ser o excesso de peso entre escolares problema de saúde relevante no município, ressaltando-se a importância de implementação de programa de intervenção precoce por parte dos gestores. Elucidar os precursores da obesidade na infância pode levar a intervenções capazes de atenuar ou impedir suas consequências na juventude e fase adulta.

Obesity, defined as an excess in body fat, is a multifactorial disease involving both genetic and environmental risk factors. Early diagnosis and interventions during critical periods of development of obesity - childhood and adolescence - have been recommended, aiming at preventing unfavorable outcomes at a later age. This cross-sectional study sought tocharacterize the lipid profile, glucose, adiponectin, leptin and ghrelin in schoolchildren between six and nine years of age with overweight and obesity in the city of Ouro Preto (MG). The data was analyzed with the Shapiro Wilk normality test, groups comparisons were made with either a parametric (T test) or a nonparametric (Mann Whitney) test, adopting confidence intervals of 95% and a significance level of ≤ 0.05. The average age of the school population was 7.8 ± 1.1 years, with a prevalence of 8.9% of overweight and 3% of obesity. Hypercholesterolemia was found in 5.5%, HDL was abnormal in 98.7%, LDL levels were borderline in 32.4% and altered glucose levels were present in 46.6% of the children. In stratified analysis by gender, higher values of leptin in girls (p = 0.032) and ghrelin in boys (p = 0.033) were found, with no difference for the other variables. The results show that overweight/obesity among schoolchildren should be considered a significant health problem in this population, highlighting the importanceof implementing early intervention programs. Uncovering the precursors of childhood obesity could lead to interventions so as to prevent or mitigate its consequences in youth and adulthood.

Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats.

Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 µg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.

Improvement of the energy supply and contractile function in normal and ischemic rat hearts by dietary orotic acid.

AIMS: As cardiac performance is closely related to its energy supply, our study investigated the effect of the orotic acid cardioprotective agent on the pathways of energy supply, in both conditions of normal flow and ischemia. MAIN METHODS: Male Wistar rats were fed during nine days with a balanced diet only or supplemented with 1% orotic acid. KEY FINDINGS: Dietary administration of orotic acid increased the cardiac utilization of fatty acids, activity of the lipoprotein lipase, expression of the gene of peroxisome proliferator-activated receptor α and its target enzymes. In addition, orotic acid increased the myocardial uptake and incorporation of glucose, glycogen content and level of GLUT4, concentration of glycolytic metabolites and lactate production in both experimental conditions, baseline and after regional ischemia. SIGNIFICANCE: Thus, in orotic acid hearts there was a simultaneous stimulus of fatty acid oxidation and glycolytic pathway, reflected in increased energetic content even in pre-ischemia. The analysis of the cardiac contractility index showed a positive inotropic effect of orotic acid due, at least in part, to the increased availability of energy. The result allows us to suggest that the metabolic changes induced by orotic acid result in appreciable alterations on myocardial contractile function.

Angiotensin-(1-7) Mas-receptor deficiency decreases peroxisome proliferator-activated receptor gamma expression in adipocytes.

The renin-angiotensin system is an important link between metabolic syndrome and cardiovascular diseases. Besides angiotensin II, other angiotensin peptides such as angiotensin-(1-7), have important biological activities. It has been demonstrated that angiotensin-(1-7), acting through the G protein-coupled receptor encoded by the Mas protooncogene have important actions on the cardiovascular system. However, the role of angiotensin-(1-7)-Mas axis in lipidic profile is not well established. In the present study, the adipocyte metabolism was investigated in wild type and FVB/N Mas-deficient male mice. The gene expression of peroxisome proliferator-activated receptor gamma, acetyl-CoA carboxylase and the amount of fatty acid synthase protein were reduced in the Mas-knockout mice. Serum nonesterified fatty acids of Mas-knockout showed a 50% increase in relation to wild type group. Basal and isoproterenol-stimulated lipolysis was similar between the groups, however, a significant decrease of the glycerol release (lipolytic index) in response to insulin was observed in wild type animals, while no effect of the insulin action was observed in a Mas-knockout group. The data suggest that the lack of angiotensin-(1-7) action through Mas receptor alters the response of adipocytes to insulin action. These effects might be related to decreased expression of PPARγ.

High-carbohydrate diet selectively induces tumor necrosis factor-α production in mice liver.

Obesity may represent a state of chronic low-grade inflammation associated with infiltration of adipose tissue by inflammatory cells. Tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1/JE), two important inflammatory cytokines, have been shown to be regulated according to changes in body adiposity. In this study on Swiss mice, we compared the influences of long-term high-carbohydrate (HC) or high-fat (HF) diet on adiposity, glucose tolerance, and secretion of TNF-α and MCP-1/JE by adipose tissue and liver. For 8 weeks, male Swiss mice (7-8 weeks) were fed either standard laboratory rodent diet (control group), HC diet (64% carbohydrate, 19% protein, and 11% fat), or HF diet (45% carbohydrate, 17% protein, and 38% fat), with the latter two diets having no fiber. Oral glucose tolerance test, triacylglycerol (TAG) plasma concentration, and systemic or tissue levels of the two proinflammatory cytokines were determined. Body weight increased by approximately 20% in mice fed the experimental diets compared with mice fed the control diet. Systemically, the hypercaloric diets induced hyperglycemia with impairment in glucose tolerance, elevated circulating TAG levels, and increased plasma concentrations of TNF-α and MCP-1/JE. In the target organs (adipose tissue and liver), both diets increased MCP-1/JE levels. However, the HC diet, but not the HF diet, was able to increase TNF-α concentration in the liver. These results have shown that the nature of nutrients influences the type of proinflammatory cytokines in target organs and may contribute to the comorbidities of obesity.

Improved lipid and glucose metabolism in transgenic rats with increased circulating angiotensin-(1-7).

OBJECTIVE: Obesity and diabetes remain among the world's most pervasive health problems. Although the importance of angiotensin II for metabolic regulation is well documented, the role of the angiotensin-(1-7)/Mas axis in this process is poorly understood. The aim of this study was to evaluate the effect of increased angiotensin-(1-7) plasma levels in lipid and glucose metabolism using transgenic rats that express an angiotensin-(1-7)-releasing fusion protein, TGR(A1-7)3292 (TGR). METHODS AND RESULTS: The increased angiotensin-(1-7) levels in TGR induced enhanced glucose tolerance, insulin sensitivity, and insulin-stimulated glucose uptake. In addition, TGR presented decreased triglycerides and cholesterol levels, as well as a significant decrease in abdominal fat mass, despite normal food intake. These alterations were accompanied by a marked decrease of angiotensinogen expression and increased Akt in adipose tissue. Furthermore, augmented plasma levels and expression in adipose tissue was observed for adiponectin. Accordingly, angiotensin-(1-7) stimulation increased adiponectin production by primary adipocyte culture, which was blocked by the Mas antagonist A779. Circulating insulin and muscle glycogen content were not altered in TGR. CONCLUSION: These results show that increased circulating angiotensin-(1-7) levels lead to prominent changes in glucose and lipid metabolism.

Fenofibrate prevents orotic acid--induced hepatic steatosis in rats.

The experiments performed in this report were designed to investigate the mechanisms involved in the metabolic alterations associated with orotic acid-induced hepatic steatosis and the effect of fenofibrate, a stimulant of peroxisome proliferators-activated receptor alpha (PPARalpha), on these alterations. Male Wistar rats were divided into three experimental groups: 1) fed a balanced diet (C); 2) fed a balanced diet supplemented with 1% orotic acid (OA); 3) fed OA diet containing 100 mg.kg(-1) bw.day(-1) fenofibrate (OA+F), for 9 days. Administration of OA to rats induced significant increase in the hepatic total lipids content, marked microvesicular steatosis and decrease in plasma lipids concentrations compared to control group. Fenofibrate treatment prevented fatty liver induction, caused an additional reduction on plasma lipids concentrations and caused a 40% decrease in the lipogenic rate in adipose tissue. The results also showed a 40% increase in lipoprotein lipase (LPL) activity in adipose tissue from OA treated group and fenofibrate administration induced a 50% decrease in LPL activity. The liver mRNA expression of PPARalpha and ACO (acyl CoA oxidase) were 85% and 68% decreased in OA group when compared to control, respectively. Fenofibrate treatment increased the PPARalpha and ACO expressions whereas the CPT-1 (carnitine palmitoyl transferase-1) expression was not altered. Our results have shown that fenofibrate treatment decreases the hepatic lipid content induced by OA which is mediated by an important increase in fatty acid oxidation consequent to an increase in hepatic mRNA expression of PPARalpha and ACO.

Mas deficiency in FVB/N mice produces marked changes in lipid and glycemic metabolism.

OBJECTIVE: Metabolic syndrome is characterized by the variable coexistence of obesity, hyperinsulinemia, insulin resistance, dyslipidemia, and hypertension. It is well known that angiotensin (Ang) II is importantly involved in the metabolic syndrome. However, the role of the vasodilator Ang-(1-7)/Mas axis is not known. The aim of this study was to evaluate the effect of genetic deletion of the G protein-coupled receptor, Mas, in the lipidic and glycemic metabolism in FVB/N mice. RESEARCH DESIGN AND METHODS: Plasma lipid, insulin, and cytokine concentrations were measured in FVB/N Mas-deficient and wild-type mice. A glucose tolerance test was performed by intraperitoneally injecting d-glucose into overnight-fasted mice. An insulin sensitivity test was performed by intraperitoneal injection of insulin. Uptake of 2-deoxy-[(3)H]glucose by adipocytes was used to determine the rate of glucose transport; adipose tissue GLUT4 was quantified by Western blot. Gene expression of transforming growth factor (TGF)-beta, type 1 Ang II receptor, and angiotensinogen (AGT) were measured by real-time PCR. RESULTS: Despite normal body weight, Mas-knockout (Mas-KO) mice presented dyslipidemia, increased levels of insulin and leptin, and an approximately 50% increase in abdominal fat mass. In addition, Mas gene-deleted mice presented glucose intolerance and reduced insulin sensitivity as well as a decrease in insulin-stimulated glucose uptake by adipocytes and decreased GLUT4 in adipose tissue. Mas(-/-) presented increased muscle triglycerides, while liver triglyceride levels were normal. Expression of TGF-beta and AGT genes was higher in Mas-KO animals in comparison with controls. CONCLUSIONS: These results show that Mas deficiency in FVB/N mice leads to dramatic changes in glucose and lipid metabolisms, inducing a metabolic syndrome-like state.

Effects of fenofibrate on lipid metabolism in adipose tissue of rats.

The effect of fenofibrate, a peroxisome proliferator-activated receptor alpha agonist, on body weight gain and on reduction of adipose tissue pads has been ascribed to increased fat catabolism in liver mainly through the induction of target enzymes involved in hepatic lipid metabolism. The aim of this study was to investigate whether peroxisome proliferator-activated receptor alpha activation also affects metabolic pathways in adipose tissue of rats treated with fenofibrate (100 mg/kg body weight) for 9 days. Fenofibrate lowered body weight gain and plasma triglyceride, total cholesterol, and high-density lipoprotein cholesterol but had no influence on food intake and on plasma glucose levels. The activity of lipoprotein lipase of treated animals decreased 50% in epididymal, 29% in retroperitoneal, and was not affected in the mesenteric fat pads. In this study, we show a 34% decrease in epididymal adipose tissue de novo lipogenesis by fenofibrate. The results demonstrate that insulin sensitivity of lipolysis is decreased in fenofibrate-treated rats which resulted in 30% higher rate of glycerol release when compared to the control group. These findings suggest that besides its effects on liver, fenofibrate exerts effects on lipid metabolism in adipose tissue which may contribute to decreasing adiposity.

Acute metabolic effects of thiopental anesthesia on fed and fasted rats chronically treated with bromocriptine.

We investigated the acute effects of thiopental anesthesia (4 mg/100 g, i.v.) on plasma glucose, insulin, triacylglycerol, and prolactin levels in rats treated with bromocriptine (BR) (0.4 mg/100 g body wt, i.p., for two weeks). Thiopental anesthesia induced a rapid increase in plasma insulin that was more pronounced in the animals treated with BR (116%, P <0.05). Thiopental anesthesia also produced a 55% decreased in plasma prolactin levels (P <0.01) in control fed rats, and a 22% reduction in plasma triacylglycerol (P <0.05) in both controls and BR-treated rats. We conclude that BR may constitute and additional sympatholytic factor in animals submitted to thiopental anesthesia.