Yolanda Lombardo

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C. Michael Hall

University of Canterbury/Te Whare Wānanga o Waitaha

David Seamon

Kansas State University

Remo Caponi

University of Cologne

Armando Marques-Guedes

UNL - New University of Lisbon

Lénia Marques

Erasmus University Rotterdam

Mauro Grondona

University of Genova

Rafael Domingo Osle

University of Navarra

Ken Pennington

The Catholic University of America

Jose Antonio Garcia del Castillo

Universidad Miguel Hernandez

Simón Peña-Fernández

University of the Basque Country, Euskal Herriko Unibertsitatea

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Papers by Yolanda Lombardo

[Study of serum sialic acid in normal subjects, diabetics with or without angiopathy and during hypoglycemic syndromes]

Revue européenne d'études cliniques et biologiques. European journal of clinical and biological research

Muscle Lipid Metabolism and Insulin Secretion Are Altered in Insulin-Resistant Rats Fed a High Sucrose Diet

Journal of Nutrition

Feeding rats a sucrose rich diet (SRD) induces hypertriglyceridemia and insulin resistance. The p... more Feeding rats a sucrose rich diet (SRD) induces hypertriglyceridemia and insulin resistance. The purposes of this study were to determine the time course of changes in lipid and glucose metabolism in the gastrocnemius muscle, both in the basal state and after the euglycemic hyperinsulinemic clamp, in rats fed a SRD for 3, 15 or 30 wk, and to analyze the changes in glucose-stimulated insulin secretion from perifused isolated islets from SRD-fed rats and their relationships to peripheral insulin insensitivity. A control group of rats was fed a control diet (CD) for the same period of time. After 3 wk of consuming the SRD, long-chain acyl CoA (LCACoA) levels in muscle were greater than in rats fed the CD, an early indication of the disturbance of lipid metabolism. Neither glycogen storage nor glucose oxidation were impaired at this time. Moreover, the biphasic patterns of glucose-stimulated insulin secretion showed a marked increase in the first peak, which helped maintain normoglycemia in SRD-fed rats. After 15 or 30 wk of consuming the SRD, triglyceride and LCACoA levels in muscles were greater than in rats fed the CD. Glucose oxidation as well as insulin-stimulated glycogen synthase activity and glycogen storage were lower than in rats fed the CD. Moreover, the altered pattern of insulin secretion further deteriorated. This was accompanied by peripheral insulin resistance and moderate hyperglycemia. Our results indicate that the dyslipemia present in rats chronically fed a SRD may play an important role in the progressive deterioration of insulin secretion and sensitivity in this animal model.

Inverse alterations of BCKA dehydrogenase activity in cardiac and skeletal muscles of diabetic rats

by Cynthia Serdikoff and Yolanda Lombardo

The American journal of physiology

Rat cardiac and skeletal muscles, which have been used as model tissues for studies of regulation... more Rat cardiac and skeletal muscles, which have been used as model tissues for studies of regulation of branched-chain alpha-keto acid (BCKA) oxidation, vary greatly in the activity state of their BCKA dehydrogenase. In the present experiment, we have investigated whether they also vary in response of their BCKA dehydrogenase to a metabolic alteration such as diabetes and, if so, to investigate the mechanism that underlies the difference. Diabetes was produced by depriving streptozotocin-treated rats of insulin administration for 96 h. The investigation of BCKA dehydrogenase in the skeletal muscle (gastrocnemius) showed that diabetes 1) increased its activity, 2) increased the protein and gene expressions of all of its subunits (E(1)alpha, E(1)beta, E(2)), 3) increased its activity state, 4) decreased the rate of its inactivation, and 5) decreased the protein expression of its associated kinase (BCKAD kinase) without affecting its gene expression. In sharp contrast, the investigation of BCKA dehydrogenase in the cardiac muscle showed that diabetes 1) decreased its activity, 2) had no effect on either protein or gene expression of any of its subunits, 3) decreased its activity state, 4) increased its rate of inactivation, and 5) increased both the protein and gene expressions of its associated kinase. In conclusion, our data suggest that, in diabetes, the protein expression of BCKAD kinase is downregulated posttranscriptionally in the skeletal muscle, whereas it is upregulated pretranslationally in the cardiac muscle, causing inverse alterations of BCKA dehydrogenase activity in these muscles.

[Effects of competitive substrates ans insulin on glucose uptake and utilization in isolated perfused hearts of dyslipemic rats]

Medicina

Rats chronically fed (15 weeks) a sucrose-rich diet (SRD) developed hypertriglyceridemia (hyperTg... more Rats chronically fed (15 weeks) a sucrose-rich diet (SRD) developed hypertriglyceridemia (hyperTg), increased plasma free fatty acids (FFA), impaired glucose homeostasis and insulin insensitivity. An increase of Tg and glycogen (Gly) in heart muscle was also observed. HyperTg with altered glucose metabolism could have profound effects on myocardial glucose utilization. To test this hypothesis male Wistar rats were fed a semi-synthetic SRD (w/w: 62.5% sucrose, 8% corn-oil, 17% protein), and the control group (CD) received the same semi-synthetic diet, except that sucrose was replaced with starch for 90 days. At that time, the hearts from these animals were isolated and perfused for 30 min in the presence or absence of insulin (30 mU/ml). Levels of the exogenous substrates were similar to those found in the plasma of the animal in vivo in both dietary groups (glucose 8.5 mM, palmitate 0.8 mM in SRD and glucose 5-5 mM, palmitate 0.3 mM in CD). In the absence of insulin glucose uptake was reduced (40%) and lactate release was increased (50%) in SRD hearts. Glucose oxidation was depressed mainly due to both, an increase of PDH kinase and a decrease of 60% of PDHa (active form of PDHc). Insulin in the perfusion medium improved only glucose uptake. The results suggest that at least two different mechanisms might contribute to insulin resistance and to impaired glucose metabolism in the perfused hearts of dyslipemic SRD fed rats: 1) reduced basal and insulin-stimulated glucose uptake and its utilization and 2) increased availability and oxidation of lipids (low PDHa and PDH kinase activities), which in turn decreased glucose uptake and utilization. Thus, this experimental model may be useful to study how impaired glucose homeostasis, increased plasma FFA and hyperTg could contribute to heart tissue malfunction.

Duration of feeding on a sucrose-rich diet determines metabolic and morphological changes in rat adipocytes

Journal of Applied Physiology

Duration of feeding on a sucroserich diet determines metabolic and morphological changes in rat a... more Duration of feeding on a sucroserich diet determines metabolic and morphological changes in rat adipocytes. J Appl Physiol 91: [2109][2110][2111][2112][2113][2114][2115][2116] 2001.-In this work, we studied the effect of a short-term (3 wk) and a long-term (15 wk) administration of a sucrose-rich diet (SRD) to Wistar rats on the morphological aspects and metabolic function of the epididymal adipose tissue that may contribute to the mechanism underlying the impaired glucose homeostasis and insulin resistance. The present work showed the following. 1) There was both a moderate increase of basal lipolysis and a decrease of the antilipolytic action of insulin in the adipocytes of rats fed a SRD for 3 wk. Neither size alterations nor increases in adipose tissue mass were recorded in this period. 2) There was a significant (P Ͻ 0.05) increase of epididymal weight after 15 wk on a SRD as well as a hypertrophy of adipocytes with a clear alteration in the cell size distribution. This was accompanied by a significant increase (P Ͻ 0.05) of basal and stimulated lipolysis and a marked decrease (P Ͻ 0.05) of the antilipolytic action of insulin. Moreover, these changes appear together with a worsening of both impaired glucose homeostasis and insulin resistance. Our results also indicate that the length of time on the SRD plays an important role in the evolution of the adiposity and metabolic changes observed in the fat pad. Furthermore, the latter precedes the detection of adiposity. adipose tissue; dyslipidemia; glucose intolerance; insulin resistance Address for reprint requests and other correspondence: Y. B.

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Specificity and mechanism of influence of amino acid residues on hepatic clearance of oligopeptides

Journal of Biological Chemistry

We have investigated the influence of amino acid residues on hepatic clearance of oligopeptides b... more We have investigated the influence of amino acid residues on hepatic clearance of oligopeptides by determining the rate of disappearance (nmol.(min.g liver)-1) of selective oligopeptides from the medium during isolated rat liver perfusion. (a) N terminus: the rate of disappearance of Ala-Leu was greater (p less than 0.01) than those of Gly-Leu, Phe-Leu, and Arg-Leu (208 +/- 13, 135 +/- 13, 116 +/- 12, and 127 +/- 12, respectively). (b) C terminus: the rate of disappearance of Leu-Ala (244 +/- 18) was significantly greater (p less than 0.01) than that of Leu-Gly (145 +/- 16). (c) Number of residues: with each increase in the number of alanine residues (2-4) there was a significant increase in the rate of peptide disappearance, and conversely, with each increase in the number of glycine residues (2-6) there was a significant decrease in the rate of peptide disappearance. Further studies showed no peptide transport by isolated liver plasma membrane vesicles and no significant correlation between the rates of peptide disappearance and hydrolase activities of the perfusion medium but highly significant correlation with hydrolase activity of plasma membrane. We conclude that certain amino acid residues, such as alanine, enhance hepatic clearance of oligopeptides by increasing their affinity as substrates for plasma membrane peptide hydrolases.

Efectos de los ácidos grasos polinosaturados n-3 de origen marino sobre la dislipemia y disfunción de la célula beta en ratas insulino resistentes

Role of Uncoupling Protein 2 (UCP-2) and Peroxisome Proliferation Activated- Receptor γ (PPARγ) in the β cell dysfunction of dyslipemic insulin resistant rats. Effect of fish oil

Dietary Salba seed (Salvia hispanica L) ameliorate the metabolic abnormalities of dysfunctional adipose tissue of dyslipemic insulin-resistant rats

Niveles Moderados de Aceite de Pescado Dietario Disminuyen la Adiposidad y Revierten la Resistencia Insulínica en Ratas Dislipémicas

FABICIB, 2005

Adaptación de la Celula [Beta] en Dislipemia e Insulinoresistencia Inducida por Dieta Rica en Sacarosa. Rol de la Glucoquinasa

Efecto de la semilla de Salvia hispánica L dietaria sobre la disfunción del tejido adiposo en ratas dislipémicas insulinoresistentes

Efectos de los N-3 Pufas de Origen Marino sobre Algunas Enzimas Hepáticas Claves Involucradas en el Metabolismo Lipídico en Ratas Dislipémicas

by Gustavo Hein and Yolanda Lombardo

FABICIB, 2008

Estado Oxidativo y Contenido de Leptina en el Tejido Adiposo de Ratas Alimentadas Crónicamente con una Dieta Rica en Sacarosa

FABICIB, 2010

[Toxicological effects induced by the chronic intake of brominated vegetable oils]

Archivos latinoamericanos de nutrición, 1986

Several biochemical parameters of male Wistar rats fed during 15 weeks with standard laboratory c... more Several biochemical parameters of male Wistar rats fed during 15 weeks with standard laboratory chow, supplemented with 0.1 g of brominated vegetable oil (olive, sunflower) per 100 g of diet, were compared to those of a control group fed a normal diet during the same period of time. The former group showed a significant increase of triglyceride content in both heart and soleus muscle, as well as of total and sterified cholesterol in heart muscle. This increase was accompanied by decreased plasma levels of total and HDL-cholesterol. Some of these abnormalities were similar to those observed in rats fed the same standard laboratory chow, supplemented with 0.5 g of brominated oil per 100 g of diet. The hepatic levels of triglycerides, total proteins and glycogen, as well as the weight gain and caloric intake of the animals which were fed 0.1 g of brominated oil per 100 g diet, were similar to those of the control group. In summary, the toxicologic effects observed during the chronic in...

[Chronic consumption of brominated vegetable oils: their effect on liver secretion and catabolism of plasma lipoproteins]

Archivos latinoamericanos de nutrición, 1992

We have previously reported that normal Wistar rats fed during 105 days with standard laboratory ... more We have previously reported that normal Wistar rats fed during 105 days with standard laboratory chow, supplemented with 0.5g of brominated vegetable oil (olive, sunflower) per 100 g of diet showed a significant increase of triglyceride and cholesterol content in both heart and liver. This was accompanied by a significant decrease of plasma lipid levels. Fluctuations in plasma triglyceride concentrations may be a result of either variations in the liver secretion rate of very low density lipoprotein-triglyceride (VLDL-TG), or changes in their removal rate by extrahepatic tissues or both. In the present work we have studied the contribution of both VLDL-TG secretion, and removal rates of plasma TG in the decrease of plasma TG levels, in rats fed during 105 days with a standard laboratory chow supplemented with 0.5 g per 100 g of brominated vegetable oil. VLDL-TG secretion was estimated by measuring the accumulation of plasma TG following the injection of TRITON WR 1339 and the remova...

A sucrose-rich diet affects triglyceride metabolism differently in pregnant and nonpregnant rats and has negative effects on fetal growth

The Journal of nutrition, 1996

A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To determine whether a... more A sucrose-rich diet (SRD) causes hypertriglyceridemia in nonpregnant rats. To determine whether a SRD further enhances gestational hypertriglyceridemia, female rats were divided into the following two groups: 1) rats fed a SRD (63 g sucrose/100 g), and 2) rats that received the same diet except that the sucrose was replaced by an equal amount of cornstarch (CD). Half of the rats were mated and studied at d 20 of gestation. Body weight increase did not differ between virgin rats fed either diet, but the final body weight of pregnant rats fed SRD was lower than that of rats fed CD due to fewer fetuses per litter and lower fetal and placental weights. The SRD enhanced plasma glucose and insulin concentrations in virgin but not in pregnant rats; plasma triglycerides and FFA concentrations and the rate of triglyceride secretion into the plasma were higher in pregnant than in virgin rats fed SRD, but the increase in liver triglycerides due to SRD was higher in virgin rats. Both removal ra...

$Research paper thumbnail of [Cholesterol in lipoprotein fractions in obese normolipemic women with or without reduction of glucose tolerance]$

[Cholesterol in lipoprotein fractions in obese normolipemic women with or without reduction of glucose tolerance]

Medicina, 1981

Mechanisms underlying the beneficial effect of soy protein in improving the metabolic abnormalities in the liver and skeletal muscle of dyslipemic insulin resistant rats

European Journal of Nutrition, 2014

The present study analyzes the effect of the replacement of dietary casein by soy protein on the ... more The present study analyzes the effect of the replacement of dietary casein by soy protein on the mechanisms underlying dyslipidemia, liver steatosis and altered glucose and lipid metabolism in the skeletal muscle which developed in rats fed long-term a sucrose-rich diet (SRD). Wistar rats were fed a SRD for 4 months. From months 4 to 8, half the animals continued with the SRD, and the other half were fed a SRD in which the source of protein casein was replaced by soy. The control group received a diet with cornstarch as source of carbohydrate. Compared to SRD-fed animals, the rats fed soy showed: A--in the liver: reduction of triglyceride and cholesterol storage and decreased steatosis; normalization of mature forms of the protein mass levels of SREBP-1 and the activities of lipogenic enzymes, while the protein mass level of PPAR-α and fatty acid oxidase activity increased. B-in the gastrocnemius muscle: normalization of the enhanced lipid storage and the altered glucose oxidation, improving glucose phosphorylation; decreasing protein mass level of nPKCθ in the membrane fraction; reversion of the impaired insulin-stimulated glucose transporter Glut-4, and glucose-6-phosphate and glycogen concentrations. Besides, dyslipidemia and glucose homeostasis returned to control values. This study provides new information concerning some key mechanisms related to the effect of dietary soy on hepatic lipid metabolism and insulin action in the skeletal muscle in the presence of pre-existing dyslipidemia and insulin resistance induced by a SRD.

Time course of adipose tissue dysfunction associated with antioxidant defense, inflammatory cytokines and oxidative stress in dyslipemic insulin resistant rats

by Paola Illesca and Yolanda Lombardo

Food Funct., 2015

The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated following the t... more The dysfunctional adipose tissue of rats fed a sucrose-rich diet was investigated following the time course of the development of oxidative stress, changes in proinflammatory cytokines and adiponectin levels, and their relationship with insulin resistance. We analyzed the morphometric characteristics of epididymal adipocytes, de novo lipogenesis enzyme activities and cellular antioxidant defense, inflammatory mediators, adiponectin levels and insulin resistance in rats fed a sucrose-rich diet for 3, 15 or 30 weeks and compared to those fed a control diet. The results showed a depletion of antioxidant enzyme activities in the fat pads of rats fed a sucrose-rich diet, with an increase in xanthine oxidase activity and lipid peroxidation after 3, 15 and 30 weeks on the diet. Superoxide dismutase activity and the redox state of glutathione showed a significant decrease at weeks 15 and 30. This was accompanied by visceral adiposity and enhanced lipogenic enzyme activities. An increase in the plasma levels of proinflammatory markers (TNF-α and IL-6) was recorded only after 30 weeks on the diet. A reduction in plasma adiponectin levels accompanied the time course of deterioration of whole-body insulin sensitivity. The results suggest that lipid peroxidation, depletion of antioxidant defenses and changes in inflammatory cytokines induced by a sucrose-rich diet contribute to the dysregulation of adipose tissue and insulin resistance. Finally, these results show that the progressive deterioration of adipose tissue function, which begins in the absence of both visceral adiposity and overweight, is highly dependent on the length of time on the diet.