Edurne Simón

Resveratrol regulates lipolysis via adipose triglyceride lipase.

Resveratrol has been reported to increase adrenaline-induced lipolysis in 3T3-L1 adipocytes. The general aim of the present work was to gain more insight concerning the effects of trans-resveratrol on lipid mobilization. The specific purpose was to assess the involvement of the two main lipases: adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in the activation of lipolysis induced by this molecule. For lipolysis experiments, 3T3-L1 and human SGBS adipocytes as well as adipose tissue from wild-type, ATGL knockout and HSL knockout mice were used. Moreover, gene and protein expressions of these lipases were analyzed. Resveratrol-induced free fatty acids release but not glycerol release in 3T3-L1 under basal and isoproterenol-stimulating conditions and under isoproterenol-stimulating conditions in SGBS adipocytes. When HSL was blocked by compound 76-0079, free fatty acid release was still induced by resveratrol. By contrast, in the presence of the compound C, an inhibitor of adenosine monophosphate-activated protein kinase, resveratrol effect was totally blunted. Resveratrol increased ATGL gene and protein expressions, an effect that was not observed for HSL. Resveratrol increased fatty acids release in epididymal adipose tissue from wild-type and HSL knockout mice but not in that adipose tissue from ATGL knockout mice. Taking as a whole, the present results provide novel evidence that resveratrol regulates lipolytic activity in human and murine adipocytes, as well as in white adipose tissue from mice, acting mainly on ATGL at transcriptional and posttranscriptional levels. Enzyme activation seems to be induced via adenosine monophosphate-activated protein kinase.

Nutritional Differences Between a Gluten-free Diet and a Diet Containing Equivalent Products with Gluten

The gluten-free (GF) products market represents one of the most prosperous markets in the field of food and beverages in the immediate future. Historically, counselling for celiac disease has focused on the absence of gluten in foods, however the nutritional quality of GF foodstuffs is an important aspect to consider. The aim of the present work was to compare the nutritional composition of the 206 GF rendered products most consumed in Spain, against the composition of 289 equivalent foods with gluten, and to make a comparison between the diet including GF products and the same diet with equivalent products with gluten in a 58 adult celiac population. The results of the present collaborative study pointed out differences in calorie, macronutrient, fiber, sodium, salt and cholesterol content between GF rendered and gluten-containing foodstuffs. Thus, calorie and nutrient intake in a GF diet is different when compared to its equivalent diet with gluten. Following a diet based on GF products could suppose a nutritional imbalance for celiac patients as well as for non-celiacs who follow a diet that includes many GF rendered foodstuffs.

Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet.

Conjugated linoleic acid (CLA) refers to a mixture of naturally occurring positional and geometric isomers of linoleic acid that exist in dairy products and meat. The aim of the present work was to study the effects ofc-9,t-11 andt-10,c-12 CLA isomers on body fat accumulation and serum lipids in hamsters fed an atherogenic diet. Hamsters were divided in four groups: one group was fed a chow diet (control) and the other three groups were given semi-purified atherogenic diets with 0.5% linoleic acid (LA),c-9,t-11 ort-10,c-12 CLA. Body weight and food intake were measured daily. After 6 weeks, adipose tissues from different anatomical locations and liver were dissected and weighed. Serum glucose, total cholesterol, HDL-c, LDL-c and triacylglycerol levels, as well as total and free cholesterol, triacylglycerol and phospholipid content in liver were determined by enzymatic methods. No differences in either energy intake or final body weight were found. The addition oft-10,c-12 CLA reduced fat accumulation and led to lower serum cholesterol, as compared with LA group. Nevertheless the level remained higher than in the control animals. The reduction in serum cholesterol was limited to LDL-c. This isomer also reduced triacylglycerol content in liver but did not modify serum triacylglycerol level. In summary, the present study demonstrates thatt-10,c-12 CLA is the biologically active agent when anti-obesity and hypocholesterolaemic properties of CLA are considered. In contrast, the isomerc-9,t-11 has no effect on lipid metabolism in hamsters.ResumenEl término ácido linoleico conjugado (ALC) se utiliza para designar una serie de isómeros del ácido linoleico, presentes en los lácteos y la carne, que presentan los dobles enlaces en posición conjugada. El objetivo del presente trabajo consistió en estudiar el efecto de los isómerosc-9,t-11 yt-10,c-12 del ALC sobre la acumulación de grasa corporal y los lípidos séricos, en hámsters alimentados con una dieta aterogénica. Los hámsters se distribuyeron en cuatro grupos: un grupo recibió pienso de laboratorio (control) y los otros tres grupos, dietas aterogénicas con 0,5% de ácido linoleico, ALCc-9,t-11 ó ALCt-10,c-12. Se midió diariamente la ingesta de alimento y el peso corporal. Tras 6 semanas, se diseccionaron y pesaron los tejidos adiposos de diferentes localizaciones anatómicas y el hígado. Se midieron las concentraciones séricas de glucosa, colesterol total, c-HDL, c-LDL y triglicéridos, y el contenido hepático de colesterol total y libre, triglicéridos y fosfolípidos, por métodos enzimáticos. No se encontraron diferencias significativas ni en la ingesta de energía ni en el peso corporal final. El isómerot-10,c-12 redujo la acumulación de grasa y disminuyó el colesterol total sérico; no obstante, su nivel se mantuvo por encima del de los animales control. La reducción del colesterol sérico se produjo a expensas del c-LDL. Este isómero también disminuyó el contenido hepático de triglicéridos pero no modificó los triglicéridos séricos. El presente estudio demuestra que el isómerot-10,c-12 del ALC es el biológicamente activo como agente anti-obesidad e hipocolesterolemiante. Por el contrario, el isómeroc-9,t-11 no afectó al metabolismo lipídico en hámsters.

Energy restriction with high-fat diet enriched with coconut oil gives higher UCP1 and lower white fat in rats

OBJECTIVE: To investigate the effects of overfeeding on a high fat diet, enriched in coconut oil, and the influence of food restriction on the uncoupling protein (UCP1) expression and on body fat content.DESIGN AND SUBJECTS: In experiment I, female Wistar rats were fed ad libitum either a normal-fat diet (control group, C) or a high-fat diet (HF), enriched in coconut oil, for 7 weeks. In experiment II, HF rats after finishing experiment I were fed (for 3 weeks) either the normal-fat diet (group CAHF, Control After High Fat) or food restricted diets which provided 60% of the energy intake of group CAHF: a group fed a low-energy, normal-fat diet (LENF) and another fed a low-energy, high-fat diet (LEHF).MEASUREMENTS: Body and fatty depot weights. Food intake. Protein and UCP1 levels of interscapular brown adipose tissue.RESULTS: High-fat diet feeding promoted an increase in body fat content, body weight and UCP1 levels. Energy restriction induced similar body weight reduction in groups LENF and LEHF. However, some adipose depots were more strongly reduced in the rats fed the high-fat diet enriched in coconut oil (group LEHF) than in the rats fed the normal-fat diet (Group LENF). Specific UCP1 was 2.0 (group LENF) and 3.4 (group LEHF) times higher than in controls (group CAHF).CONCLUSION: The coconut-oil enriched diet is effective in stimulating UCP1 expression during ad libitum feeding and in preventing its down regulation during food restriction, and this goes hand in hand with a decrease of the white fat stores.

Role of Baseline Leptin and Ghrelin Levels on Body Weight and Fat Mass Changes after an Energy-Restricted Diet Intervention in Obese Women: Effects on Energy Metabolism

CONTEXT Hormones related to energy balance control may play an important role on weight loss resistance after low-caloric diet (LCD) intervention. OBJECTIVE To investigate the predictive value of baseline leptin and ghrelin on body fat mass (FM) loss after 12 wk of LCD intervention and to study whether these associations could be related to changes in resting metabolic rate (RMR). DESIGN The study comprised a total of 78 obese women (age 36.7 ± 7 yr). We measured, before and after the LCD intervention, FM (dual-energy x-ray absorptiometry) and RMR (kilojoules per kilogram body weight per day, indirect calorimetry). We also analyzed fasting serum leptin and ghrelin, and leptin to ghrelin ratio was calculated. MAIN OUTCOME MEASURES FM and RMR changes (data at baseline - data after the intervention) were assessed. RESULTS Baseline serum leptin (r = -0.301; age- and baseline FM-adjusted P = 0.009) and ghrelin (r = 0.314, adjusted P = 0.014) levels as well as leptin to ghrelin levels (r = -0.331; adjusted P = 0.009) were significantly correlated with FM changes. Leptin to ghrelin ratio was significantly correlated with RMR at baseline and after the LCD (both P < 0.010). Baseline leptin to ghrelin ratio significantly predicted changes in RMR after the LCD (r = 0.298; P = 0.019) regardless of age, baseline RMR, and total body weight (r = 0.307; P = 0.016) or FM loss (r = 0.312; P = 0.015). CONCLUSIONS Obese women with higher leptin and lower ghrelin levels at baseline seem to be more resistant to FM loss. The leptin to ghrelin ratio could be proposed as a biomarker for predicting metabolic adaptations to energy restriction treatment and, if confirmed in future studies, as a predictor of treatment success/failure.

A comparison between CLNA and CLA effects on body fat, serum parameters and liver composition

The potential of conjugated linoleic acid (CLA) as an anti-obesity molecule for humans is still a matter for debate. Thus, a great deal of scientific work is focussed on the research of new effective molecules without deleterious effects on health. The aim of the present work was to analyse the effects of jacaranda seed oil, rich in a conjugated linolenic acid (CLNA), jacaric acid (cis-8,trans-10,cis-12), on body fat, serum parameters and liver composition in rats, and to compare these effects with those oftrans-10,cis-12 CLA. Twenty-six male Wistar rats were divided into three groups fed with high-fat diets, supplemented or not (control group) with 0.5%trans-10,cis-12 CLA (CLA group) or 0.5% jacaric acid (CLNA group) for 7 weeks. No statistical differences in food intake or in final body weight were found. Whereas CLA reduced adipose tissue size, CLNA did not. Both CLA and CLNA significantly reduced non-HDL-cholesterol. In spite of a lack of significant changes in glucose and insulin levels, HOMA-IR index was significantly increased, as well as did non-esterified fatty acid levels in CLNA-fed rats. No changes in liver composition were observed. In conclusion, under our experimental conditions, jacaric acid, unlike CLA, does not show a body-fat lowering effect. Even though it leads to a healthy lipoprotein profile, it impairs insulin function. Consequently, it cannot be proposed as an anti-obesity molecule.ResumenEl potencial del ácido linoleico conjugado (CLA) como molécula anti-obesidad para seres humanos sigue siendo una cuestión en debate. Por ello, gran cantidad de trabajos científicos se centra en la investigación de nuevas moléculas eficaces y sin efectos nocivos sobre la salud. El objectivo del presente trabajo fue estudiar, en rata, los efectors del aceite de semillas de jacaranda, rico en un ácido linolénico conjugado (CLNA), el ácido jacárico (cis-8,trans-10,cis-12), sobre la grasa corporal, parámetros séricos y la composición del hígado, y comparar estos efectos con los deltrans-10,cis-12, CLA. Se utilizaron 26 ratas Wistar macho divididas en tres grupos que fueron alimentados durante 7 semanas con dietas hipergrasas, suplementadas o no (grupo control) al 0,5% con eltrans-10,cis-12 CLA (grupo CLA) o al 0,5% con el ácido jacárico (grupo CLNA). No se encontraron diferencias significativas en la ingesta de dieta, ni en el peso corporal final, ni en la composición del hígado. El CLA redujo la masa adiposa, pero no lo hizo el CLNA. Ambos disminuyeron significativamente el colesterol no-HDL. A pesar de la ausencia de cambios significativos en la glucemia e insulinemia, el índice HOMA-IR y los niveles séricos de AGL aumentaron significativamente en las ratas alimentadas con CLNA. En conclusión, en nuestras condiciones experimentales, el ácido jacárico, a diferencia del CLA, no muestra un efecto reductor de la grasa corporal. A pesar de que mejora el perfil de lipoproteínas, altera la función insulínica. Por lo tanto, este CLNA no puede ser propuesto como una molécula antiobesidad.

Association of circulating visfatin concentrations with insulin resistance and low-grade inflammation after dietary energy restriction in Spanish obese non-diabetic women: Role of body composition changes

BACKGROUND AND AIMS To assess the influence of body composition changes on circulating serum visfatin after following 12 weeks of energy restricted diet intervention. We also examined the possible role of visfatin in glucose metabolism and in obesity-associated low-grade inflammation. METHODS AND RESULTS A total of 78 obese (BMI 34.0 ± 2.8 kg/m²) women aged 36.7±7 y volunteered to participate in the study. We measured by DXA body fat mass (FM) and lean mass (LM). Fasting serum visfatin, glucose, insulin, adiponectin, leptin, IL-1β, IL-6, IL-8, TNF-α and CRP concentrations were analyzed before and after the intervention and HOMA and QUIKI indexes were calculated. Mean weight loss 7.7 ± 3.0 kg and HOMA decreased in 24 ± 35%. Serum visfatin concentration change was negatively associated with LM difference (P < 0.05), whereas no significant relationship was observed with FM changes after energy restricted diet intervention. Changes in circulating serum visfatin levels were significantly and inversely associated with HOMA-IR (P < 0.01) and positively with QUICKI index (P < 0.02) after energy restricted diet intervention, regardless of achieved body weight loss. We did not find any significant association between changes in visfatin levels and IL-1β, IL-6, IL-8, TNF-α and CRP levels after dietary intervention (all P > 0.2). CONCLUSION Circulating visfatin concentration is associated with sensitivity improvement achieved after energy restricted diet intervention induced weight loss. Furthermore, LM changes could be an influencing factor on visfatin concentrations and consequently, on the improvement of insulin sensitivity after weight loss in obese non-diabetic women. Our findings did not provide any evidence for a role of visfatin increase on low-grade inflammation after weight loss.

Hepatomegaly Induced by Trans-10,cis-12 Conjugated Linoleic Acid in Adult Hamsters Fed an Atherogenic Diet Is Not Associated with Steatosis

Objective: To study the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on liver size and composition, as well as on hepatic lipogenesis and fatty acid oxidation, in adult hamsters. Methods: Sixteen male Syrian Golden hamsters (8-month-old; initial body weight 167 ± 5 g) were divided into two groups and fed on atherogenic diets supplemented either with 0.5% linoleic acid or trans-10,cis-12 CLA, for 6 weeks. Liver lipids, fatty acid profile, protein, water and DNA contents were analysed. The activity and expression of several enzymes involved in liver fatty oxidation and lipogenesis were assessed, as was the expression of transcriptional factors controlling these enzymes. Results: The addition of CLA to the diet led to significantly greater liver weight due to hyperplasia. No changes were observed in liver composition. CLA did not modify the expression or the activity of analysed oxidative enzymes. With regard to lipogenic enzymes, an increase in the expression and the activity of acetyl-CoA carboxylase was found. Conclusions: These results show that the expected body fat-lowering effect of trans-10,cis-12 CLA, observed in young rodents, is not found in adult hamsters. The lack of increase in liver fatty acid oxidation, help to explain why that effect was not found in these animals. Further, the CLA treatment-induced hepatomegaly is a consequence of hyperplasia.

Effects of medium-chain fatty acids on body composition and protein metabolism in overweight rats.

The lack of efficiency of classical treatments for obesity has led to propose alternative strategies. In order to obtain information about the effects of dietary fatty acid composition on body fat and protein metabolism, overweight female rats were fed on isoenergetic diets, using either medium-chain (MCT) or long-chain (LCT) triglycerides as a lipid source. After 23 days, the MCT group had mildly decreased body weight but greatly reduced adipose tissue depots. All fat depots were significantly diminished. MCT-fed rats showed a decrease in some hormones involved in energy balance, such as leptin and triiodothyronine. Feeding MCT resulted in improvements in nitrogen balance. Muscle protein content was similar in both treatments despite an increase in protein degradation in the MCT group. The present data clearly show that a diet with MCT as lipid fuel depresses weight gain and fat stores, relative to a standard LCT diet.ResumenLa falta de eficacia de las dietas tradicionales en el tratamiento de la obesidad ha llevado a proponer estrategias alternativas. Con el objetivo de obtener información en ácidos grasos de la dieta sobre la grasa corporal y el metabolismo proteico, se alimentan ratas hembra con sobrepeso con dietas isoenergéticas que contienen triglicéridos con ácidos grasos de cadena media (MCT) o larga (LCT) como fuente lipídica. Tras 23 días, el grupo MCT muestra un descenso en el peso corporal junto con una importante reducción del depósito lipídico. Todas las localizaciones adiposas estudiadas se reducen significativamente. Este grupo MCT presenta menor concentración de algunas hormonas implicadas en el balance energético, tales como la leptina y la triyodotironina. La alimentación con MCT consigue mejora en el balance de nitrógeno. El contenido proteico muscular resulta similar en ambos grupos, aunque el grupo MCT muestra una mayor degradación proteica. Estos resultados muestran claramente que una dieta con MCT como fuente lipídica, frente a una dieta con LCT, reduce los depósitos grasos, ralentizando la ganancia de peso.

The combination of resveratrol and CLA does not increase the delipidating effect of each molecule in 3T3-L1 adipocytes

INTRODUCTION Trans-10, cis-12 conjugated linoleic acid (CLA) and resveratrol have been shown to reduce TG content in cultured 3T3-L1 adipocyte acting on different pathways. In recent years, the method of simultaneously targeting several signal transduction pathways with multiple natural products in order to achieve additive or synergistic effects has been tested. However, the combined effect of both molecules on lipid metabolism has not been described before. OBJECTIVE The aim of the present work was to analyze the effect of the combination of trans-10, cis-12 CLA and resveratrol on TG accumulation as well as on FAS, HSL and ATGL expression in 3T3-L1 mature adipocytes, in order to assess a potential interaction between both molecules. METHODS For this purpose, 3T3-L1 mature adipocytes were treated with the two molecules, both separately and combined, in 10 and 100 μM for 20 hours. TG content and FAS, ATGL and HSL expression were measured by spectrophotometry and Real Time RT-PCR respectively. RESULTS Both doses of CLA and 100 M resveratrol decreased TG content in mature adipocytes. The combination of both molecules reduced TG accumulation to the same extent as each one separately. No change in FAS and HSL mRNA levels after CLA and resveratrol treatment was observed. ATGL was not modified by CLA but it was increased by resveratrol and by the combination. This combination did not increase the effect caused by resveratrol on its own. CONCLUSION Lipolysis increase via ATGL is involved in the TG reduction induced by resveratrol and the combination of both molecules. The combination of these two molecules does not increase the efficacy of each molecule separately in mature adipocytes and thus it does not represent an advantage for obesity treatment or prevention.