RESUMEN
Adiponectin, an adipocyte-derived plasma protein, has been shown to play an important role in the regulation of fatty acid and glucose metabolism. Adiponectin enhances fatty acid oxidation both in skeletal and cardiac muscle as well as in the liver, thus reducing triglyceride content in these tissues. Moreover, it stimulates glucose uptake by skeletal and cardiac muscle, and inhibits glucose production by the liver; consequently decreasing blood glucose levels. This review focuses on the molecular mechanisms underlying adiponectin effects on carbohydrate and lipid metabolism in skeletal muscle, cardiac muscle and liver.
Asunto(s)
Adiponectina/metabolismo , Metabolismo de los Hidratos de Carbono , Metabolismo de los Lípidos , Adiponectina/biosíntesis , Adiponectina/genética , Animales , Humanos , Hígado/metabolismo , Músculo Esquelético/metabolismo , Miocardio/metabolismoRESUMEN
Weight cycling is one of the widely used weight reduction strategies; however, the adverse effects of this method include regaining significant amounts of weight. The molecular mechanisms underlying weight gain following cycles of dietary deprivation and refeeding are still poorly understood. One of the possibilities is that repeated loss and gain of weight may promote fat deposition in adipose tissue. To test this hypothesis we investigated serum leptin levels and lipogenic enzyme activities in white adipose tissue (WAT) of male Wistar rats during 12 days of ad libitum feeding following multiple cycles of alternating food deprivation and refeeding. Rats subjected to eight cycles of food deprivation and refeeding (MFR group) showed significantly decreased circulating leptin levels when compared with control rats (nearly 50% decrease in leptin levels, P < 0.01). Throughout 12 days of ad libitum feeding, serum leptin levels increased modestly but remained significantly (24%, P < 0.05) lower than control levels. Fatty acid synthase (FAS) and malic enzyme (ME) activities (chosen as representatives of enzymes directly involved in fatty acid synthesis) were found to be considerably higher in WAT of MFR rats refed for 3 days in comparison to control rats, and remained elevated even after 12 days of refeeding. These observations suggest that the elevation of lipogenic enzyme activities induced by multiple cycles of dietary deprivation followed by refeeding persists for several days, markedly increasing the lipogenic capacity of adipose tissue, which, accompanied by a decrease in circulating leptin levels, may promote weight gain.
Asunto(s)
Tejido Adiposo Blanco/enzimología , Ácido Graso Sintasas/metabolismo , Leptina/sangre , Malato Deshidrogenasa/metabolismo , Tejido Adiposo Blanco/anatomía & histología , Tejido Adiposo Blanco/metabolismo , Animales , Glucemia/metabolismo , Dieta Reductora , Epidídimo/enzimología , Epidídimo/metabolismo , Privación de Alimentos , Insulina/sangre , Lípidos/biosíntesis , Masculino , Tamaño de los Órganos , Ratas , Ratas Wistar , Aumento de Peso , Pérdida de PesoRESUMEN
We compared concentrations of nucleotide substrates and activities of enzymes of nucleotide metabolism in pig and human blood, heart, and kidney. The most important difference was lower ecto-5-nucleotidase (ESN) activity in both pig hearts and kidney. Furthermore, higher hypoxanthine, inosine, adenine, and uracil, but lower uridine and uric acid concentrations were observed in pig blood as compared to human. A twofold increase in UTP concentration has been observed in pig hearts following 4 h perfusion with human blood. Purine metabolism is an important target for genetic and pharmacological manipulation during xenotransplantations.
Asunto(s)
Purinas/metabolismo , Trasplante Heterólogo/métodos , 5'-Nucleotidasa/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Animales Modificados Genéticamente , Cromatografía Líquida de Alta Presión , Humanos , Riñón/metabolismo , Miocardio/metabolismo , Especificidad de la Especie , Porcinos , Uridina Trifosfato/metabolismoRESUMEN
Ecto-5'-nucleotidase (E5'N) is an extracellular enzyme forming anti-inflammatory and immunosuppressive adenosine. We evaluated whether confrontation of pig heart and endothelial cells with human blood changes the activity of E5'N. Pig hearts were perfused ex vivo with fresh human blood for 4 h. Pig aortic endothelial cells (PAEC) were incubated in vitro with human plasma for 3 h. Ex vivo perfusion of pig heart with fresh human blood resulted in a decrease in E5'N activity to 62% and 61% of initial in wild-type and transgenic pig hearts, respectively. PAEC activity of E5'N decreased to 71% and 50% of initial after 3 h exposure to heat-inactivated and active complement human plasma, respectively, while it remained constant in controls. Pig heart activity of E5'N decreased following exposure to human blood, which may affect adenosine production and exacerbate hyperacute and vascular rejection.
Asunto(s)
5'-Nucleotidasa/antagonistas & inhibidores , 5'-Nucleotidasa/metabolismo , Sangre/metabolismo , Endotelio Vascular/metabolismo , Animales , Animales Modificados Genéticamente , Aorta/metabolismo , Proteínas del Sistema Complemento , Endotelio Vascular/citología , Humanos , Nucleótidos/química , Perfusión , Transducción de Señal , Especificidad de la Especie , Porcinos , Factores de Tiempo , Trasplante HeterólogoRESUMEN
Recently, we have found that despite the significant reduction of body weight after multiple starvation-refeeding cycles, white adipose tissue (WAT) exhibits surprisingly high rates of lipogenesis and lipogenic enzyme activities. The purpose of this study was to determine the response of WAT lipogenic enzyme mRNAs of rats subjected to multiple cycles of 3 days fasting and 3 days of refeeding. Despite the body weight reduction, significant increase of lipogenic enzymes (ie, fatty acid synthase [FAS], acetyl-coenzyme A [CoA] carboxylase [ACC], adenosine triphosphate (ATP)-citrate lyase [ACL], NADP-linked malic enzyme [ME], and glucose 6-phosphate dehydrogenase [G6PDH]) mRNAs in WAT was found after multiple cycles of starvation-refeeding of rats on standard laboratory diet. These findings, together with the results published recently, indicate that multiple cycles of starvation-refeeding cause the increased lipogenesis in WAT by upregulation of the lipogenic enzymes gene expression.
Asunto(s)
Tejido Adiposo/enzimología , Ingestión de Alimentos , Ácido Graso Sintasas/metabolismo , Privación de Alimentos , Regulación Enzimológica de la Expresión Génica , Animales , Ácido Graso Sintasas/análisis , Masculino , ARN Mensajero/análisis , Ratas , Ratas Wistar , Regulación hacia ArribaRESUMEN
The effect of multiple cycles of starvation-refeeding on rat body weight and on plasma lipid concentration was studied. After 1 cycle of starvation-refeeding, the rat body weight did not change significantly; however the postprandial plasma triacylglycerol concentration decreased approximately 2-fold as compared to rats fed ad libitum. After 8 cycles of starvation-refeeding, both rat body weight and plasma triacylglycerols concentration decreased. In contrast, the plasma cholesterol (both total and HDL cholesterol) concentration did not change appreciably either after 1 or 8 cycles of starvation-refeeding as compared to control. Although the postprandial plasma triacylglycerol concentration decreased in both groups (i.e. after 1 and 8 cycles of starvation-refeeding), this phenomenon appears to last longer after 8 cycles of starvation-refeeding. The epididymal white adipose tissue weight decreased after both 1 and 8 cycles of starvation-refeeding. After 1 cycle of starvation-refeeding followed by 3, 6 and 9 days of ad libitum feeding, the epididymal white adipose tissue weight increased progressively, reaching the control value at day 9. In contrast, after 8 cycles of starvation-refeeding followed by 9 days of ad libitum feeding, the epididymal white adipose tissue weight did not reach the control value. These results suggest that dieting is associated with body and adipose tissue weight loss as well as with the decrease of plasma triacylglycerol concentration. Furthermore, our results suggest that better maintenance of low adipose tissue weight and low plasma triacylglycerol concentration may be achieved after multiple cycles of starvation-refeeding.
Asunto(s)
Periodo Posprandial/fisiología , Inanición/metabolismo , Triglicéridos/sangre , Tejido Adiposo/anatomía & histología , Tejido Adiposo/fisiología , Animales , Colesterol/sangre , Dieta , Masculino , Tamaño de los Órganos/fisiología , Ratas , Ratas WistarRESUMEN
BACKGROUND: Anorexia and weight loss frequently accompany chronic renal failure (CRF). Although multiple metabolic changes occur during CRF, a bulk of evidence indicates that the decrease in caloric intake plays a major role in CRF-induced weight loss. Recently, it has been suggested that elevated plasma leptin concentrations could contribute to anorexia and to downregulation of leptin gene expression in CRF patients. However, in some CRF patients, plasma leptin concentrations have been found to be lower than one could expect. Thus we assumed that inhibition of leptin synthesis plays an important role in the regulation of plasma leptin concentrations in CRF patients. METHODS: To test this assumption, the leptin mRNA level in rat white adipose tissue from ad-libitum-fed control (sham operated), pair-fed control (sham operated) and rats with experimentally induced CRF has been measured by Northern blotting analysis. In addition, serum leptin concentration (by radioimmunoassay) was determined in all three groups of animals. RESULTS: The results of the present study indicate that in experimental CRF the leptin mRNA level is decreased by about 50% as compared to the sham-operated animals (ad-libitum-fed and pair-fed controls). The mean serum leptin concentration in CRF rats was essentially similar to the leptin concentration in sham-operated ones. CONCLUSION: The data obtained suggest that in CRF animals the serum leptin concentration might be affected not only by the decrease in leptin removal in the kidney, but also by the decrease in leptin secretion from adipose tissue. Furthermore, the results of the study suggest that leptin may be only one of many factors involved in the pathogenesis of malnutrition associated with CRF.
Asunto(s)
Tejido Adiposo/metabolismo , Fallo Renal Crónico/metabolismo , Leptina/genética , ARN Mensajero/metabolismo , Animales , Fallo Renal Crónico/sangre , Leptina/sangre , Masculino , Nefrectomía , Concentración Osmolar , Periodo Posoperatorio , Ratas , Ratas Wistar , Valores de ReferenciaRESUMEN
Regulation of some lipogenic enzyme gene expression by clofibrate was studied in rat white and brown adipose tissue. In white adipose tissue the drug administration for 14 days to rats resulted in the increase in acetyl-CoA carboxylase, ATP-citrate lyase, and glucose 6-phosphate dehydrogenase mRNA levels. Opposing effect of clofibrate on the acetyl-CoA carboxylase, ATP-citrate lyase, and glucose 6-phosphate dehydrogenase mRNA levels was found in brown adipose tissue. These data indicate a tissue specificity of clofibrate action on lipogenic enzyme gene expression. The results presented in this paper provide further evidence that hypolipidaemia caused by the treatment with clofibrate cannot be related to the inhibition of fatty acid synthesis in white adipose tissue in rat.
Asunto(s)
Acetil-CoA Carboxilasa/genética , Tejido Adiposo/efectos de los fármacos , Anticolesterolemiantes/farmacología , Clofibrato/farmacología , ARN Mensajero/análisis , Tejido Adiposo/enzimología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/enzimología , Animales , Glucosafosfato Deshidrogenasa/genética , Masculino , Ratas , Ratas Wistar , Receptores Citoplasmáticos y Nucleares/fisiología , Factores de Transcripción/fisiologíaRESUMEN
Two previous studies have reported contradictory results regarding the effect of fibrates treatment on obese (ob) gene expression in rodents. The purpose of the present study was to reinvestigate this issue. We examined the effect of clofibrate (fibrate derivative) administration for 14 days to rats on malic enzyme (as an adequate control of fibrates action) and leptin mRNAs level in the white and brown adipose tissues (WAT and BAT, respectively). The malic enzyme activity and malic enzyme mRNA level in white adipose tissue increased significantly after clofibrate feeding. In brown adipose tissue, the drug treatment resulted in depression of malic enzyme activity and malic enzyme mRNA level. Under the same conditions, leptin mRNA level did not change in these tissues. The results presented in this paper provide further evidence that the clofibrate (activator of peroxisome proliferator activated receptor alpha), feeding is without effect on ob gene expression in rat white and brown adipose tissue. Furthermore, the present study demonstrates that clofibrate causes opposite effects on malic enzyme gene expression in WAT (up-regulation) and BAT (down-regulation).
Asunto(s)
Tejido Adiposo Pardo/metabolismo , Tejido Adiposo/metabolismo , Clofibrato/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Leptina/genética , Malato Deshidrogenasa/genética , Transcripción Genética/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Animales , Secuencia de Bases , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos Antisentido , ARN Mensajero/genética , ARN Ribosómico 18S/genética , Ratas , Ratas WistarRESUMEN
Fibrate derivatives are commonly used to treat hyperlipidaemia; however, the mechanism of the antilipidaemic action of these drugs is still unknown. The effect of clofibrate (fibrate derivative) administration for 14 days on lipogenesis and on malic enzyme (EC 1.1.1.40) and fatty acid synthase (EC 2.3.1.85) gene expression in brown and white adipose tissues and in the liver was examined in rats. The rate of brown adipose tissue lipogenesis in the clofibrate-treated animals was significantly lower than that of the control rats. The rate of liver and white adipose tissue lipogenesis was not affected significantly by clofibrate. In brown adipose tissue, the drug treatment resulted in a depression of fatty acid synthase and malic enzyme mRNA levels. The fatty acid synthase mRNA level did not change significantly in the liver, whereas the malic enzyme mRNA level increased approximately 6-fold in this organ after clofibrate treatment. The malic enzyme mRNA level in white adipose tissue increased about 2-fold, while the fatty acid synthase mRNA level was unchanged after clofibrate feeding. The results presented in this paper provide further evidence that the hypolipidaemia caused by treatment of rats with clofibrate cannot be related to the inhibition of fatty acid synthesis in the liver and white adipose tissue. These data also indicate that clofibrate exhibits tissue specificity.
Asunto(s)
Tejido Adiposo Pardo/enzimología , Tejido Adiposo/metabolismo , Clofibrato/farmacología , Ácido Graso Sintasas/metabolismo , Regulación Enzimológica de la Expresión Génica , Lípidos/biosíntesis , Hígado/enzimología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/enzimología , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Pardo/metabolismo , Animales , Northern Blotting , Colesterol/sangre , Ácido Graso Sintasas/genética , Hipolipemiantes/farmacología , Lípidos/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Malato Deshidrogenasa/genética , Malato Deshidrogenasa/metabolismo , Masculino , Especificidad de Órganos/genética , ARN/aislamiento & purificación , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Triglicéridos/sangreRESUMEN
The purpose of the study was to determine the response of liver and brown (BAT) and white (WAT) adipose tissue lipogenesis and total body weight in rats subjected to multiple cycles of 3 days of fasting and 3 days of refeeding. Rats fasted for 3 days showed significant reduction in body weight. These changes were reversed on 3 days' refeeding. Body weight was much higher in rats fed ad libitum than in animals experiencing more than one cycle of 3 days of fasting followed by 3 days of refeeding. Despite the significant body weight reduction, an unusual increase of lipogenesis in WAT was found after multiple cycles of starvation-refeeding of rats on standard laboratory diet. The rate of lipogenesis in the liver and BAT was also elevated but to a much smaller extent. A parallel increase in enzymatic activities related to fatty acid synthesis, ie, fatty acid synthase, acetyl-coenzyme A carboxylase, adenosine triphosphate (ATP)-citrate lyase, NADP-linked malic enzyme, and hexose monophosphate shunt dehydrogenases, suggests that the increased rate of lipogenesis in WAT is a consequence of increased lipogenic enzyme activities. These data suggest that upregulation of WAT lipogenesis occurs after the multiple cycles of the starvation-refeeding protocol. An unusual increase of lipogenesis in rat WAT may have a survival advantage, because starved-refed rats must develop the ability to ingest large amounts of food during a refeeding period to store it in a convenient form than can be used as an oxidizable substrate during a period of starvation. Moreover, these results suggest that it is possible to develop appropriate starvation-refeeding conditions that may inhibit body weight gain.
Asunto(s)
Tejido Adiposo/metabolismo , Ingestión de Alimentos/fisiología , Metabolismo de los Lípidos , Inanición/fisiopatología , Tejido Adiposo/enzimología , Tejido Adiposo/fisiología , Tejido Adiposo Pardo/química , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/fisiología , Animales , Peso Corporal/fisiología , Ácido Graso Sintasas/metabolismo , Hígado/química , Hígado/metabolismo , Hígado/fisiología , Malato Deshidrogenasa/metabolismo , Masculino , Ratas , Ratas Wistar , Factores de Tiempo , Aumento de Peso/fisiologíaAsunto(s)
Obesidad/genética , Tejido Adiposo/metabolismo , Animales , Índice de Masa Corporal , Sistema Nervioso Central/metabolismo , Diabetes Mellitus/metabolismo , Humanos , Interleucina-6/metabolismo , Leptina , Hormonas Estimuladoras de los Melanocitos/metabolismo , Mutación , Neuropéptido Y/metabolismo , Obesidad/metabolismo , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/análisis , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The secondary structure of human brain cytosolic and mitochondrial 'malic' enzymes purified to homogeneity has been investigated by Fourier-transform IR spectroscopy. The absorbance IR spectra of these two isoenzymes were slightly different, but calculated secondary-structure compositions were essentially similar (38% alpha-helix, 38-39% beta-sheet, 14% beta-turn and 9-10% random structure). These proportions were not affected by succinate, a positive effector of mitochondrial 'malic' enzyme activity. IR spectra indicate that the tertiary structures of human brain cytosolic and mitochondrial 'malic' enzymes are slightly different, and addition of succinate does not cause conformational changes to the tertiary structure of the mitochondrial enzyme. Thermal-denaturation patterns of the cytosolic and mitochondrial enzymes, obtained from spectra recorded at different temperatures in the absence or presence of Mg2+, suggest that the tertiary structure of both isoenzymes is stabilized by bivalent cations and that the cytosolic enzyme possesses a more compact tertiary structure.
Asunto(s)
Encéfalo/enzimología , Malato Deshidrogenasa/química , Citosol/enzimología , Humanos , Mitocondrias/enzimología , Estructura Secundaria de Proteína , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The maximum activity and intracellular distribution of NADP(+)-linked malic enzyme in brain of Mammalia, Aves, Reptilia, Amphibia and Pisces are reported. Malic enzyme activity was present in all animals brains investigated. Most of the enzyme activity was located in the mitochondrial fraction. In brain of endothermic animals the activity of malic enzyme was several-fold higher than in ectothermic animals. Other NADPH-producing enzymes (i.e. NADP(+)-linked isocitrate dehydrogenase and hexosemonophosphate shunt dehydrogenase) activities were essentially similar in all animals brains tested. However, the total potential capability of NADPH production was lower in ectothermic animals (due mainly to lower malic enzyme activity). It is suggested that the presence of NADP(+)-linked malic enzyme in the brain may be related mainly to mitochondrial metabolism, especially to maintain the mitochondrial pool of NADP+ in reduced form.