Exercise improves lipid metabolism disorders induced by high-fat diet in a SESN2/JNK-independent manner.

SESN2 and JNK are emerging powerful stress-inducible proteins in regulating lipid metabolism. The aim of this study was to determine the underlying mechanism of SESN2/JNK signaling in exercise to improve lipid disorder induced by high-fat diet (HFD). Our data showed that HFD and SESN2 knockout resulted in abnormalities including elevated body weight, increased fat mass, serum total cholesterol, lipid biosynthesis related proteins, and a concomitant increase of pJNK-Thr183/Tyr185. The above changes were reversed by exercise training. SESN2 silencing or JNK inhibition in palmitate-treated C2C12 further confirmed that SESN2 and JNK play a vital role in lipid biosynthesis. Rescue experiment further demonstrated that SESN2 reduced lipid biosynthesis through inhibition of JNK. SESN2/JNK signaling axis regulates lipid biosynthesis in both animal and cell models with abnormalities of lipid metabolism induced by HFD or palmitate treatment. This study provided evidence that exercise ameliorated lipid metabolic disorder induced by HFD feeding or by SESN2 knockout. SESN2 may improve lipid metabolism through inhibition JNK expression in skeletal muscle cells, providing a molecular mechanism that may represent an attractive target for the treatment of lipid disorder. Novelty: Exercise improved lipid disorder induced by HFD feeding and SESN2 knockout. SESN2 and JNK play a vital role in lipid biosynthesis in vivo and in vitro. SESN2 suppressed JNK to improve lipid metabolism in skeletal muscle cells.

Ursodeoxycholyl lysophosphatidylethanolamide protects against hepatic ischemia/reperfusion injury via phospholipid metabolism-mediated mitochondrial quality control.

Mitochondrial dysfunction is the leading cause of reactive oxygen species (ROS) burst and apoptosis in hepatic ischemia/reperfusion (I/R) injury. Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatotargeted agent that exerts hepatoprotective roles by regulating lipid metabolism. Our previous studies have shown that UDCA-LPE improves hepatic I/R injury by inhibiting apoptosis and inflammation. However, the role of UDCA-LPE in lipid metabolism and mitochondrial function in hepatic I/R remains unknown. In the present study, we investigated the role of UDCA-LPE in hepatic I/R by focusing on the interface of phospholipid metabolism and mitochondrial homeostasis. Livers from 28-week-old mice, primary hepatocytes and HepG2 cells were subjected to in vivo and in vitro I/R, respectively. Analyses of oxidative stress, imaging, ATP generation, genetics, and lipidomics showed that I/R was associated with mitochondrial dysfunction and a reduction in phospholipids. UDCA-LPE alleviated mitochondria-dependent oxidative stress and apoptosis and prevented the decrease of phospholipid levels. Our study found that cytosolic phospholipase A2 (cPLA2 ), a phospholipase that is activated during I/R, hydrolyzed mitochondrial membrane phospholipids and led to mitochondria-mediated oxidative stress and apoptosis. UDCA-LPE inhibited the interaction between cPLA2 and mitochondria and reduced phospholipid hydrolysis-mediated injury. UDCA-LPE might regulate the crosstalk between the phospholipid metabolism and the mitochondria, restore mitochondrial function and ameliorate I/R injury.

Vegetable lecithins: A review of their compositional diversity, impact on lipid metabolism and potential in cardiometabolic disease prevention.

Vegetable lecithins, widely used in the food industry as emulsifiers, are a mixture of naturally occurring lipids containing more than 50% of phospholipids (PL). PL exert numerous important physiological effects. Their amphiphilic nature notably enables them to stabilise endogenous lipid droplets, conferring them an important role in lipoprotein transport, functionality and metabolism. In addition, beneficial effects of dietary lecithin on metabolic disorders have been reported since the 1990s. This review attempts to summarize the effects of various vegetable lecithins on lipid and lipoprotein metabolism, as well as their potential application in the treatment of dyslipidemia associated with metabolic disorders. Despite controversial data concerning the impact of vegetable lecithins on lipid digestion and intestinal absorption, the beneficial effect of lecithin supplementation on plasma and hepatic lipoprotein and cholesterol levels is unequivocal. This is especially true in hyperlipidemic patients. Furthermore, the immense compositional diversity of vegetable lecithins endows them with a vast range of biochemical and biological properties, which remain to be explored in detail. Data on the effects of vegetable lecithins alternative to soybean, both as supplements and as ingredients in different foods, is undoubtedly lacking. Given the exponential demand for vegetable products alternative to those of animal origin, it is of primordial importance that future research is undertaken in order to elucidate the mechanisms by which individual fatty acids and PL from various vegetable lecithins modulate lipid metabolism. The extent to which they may influence parameters associated with metabolic disorders, such as intestinal integrity, low-grade inflammation and gut microbiota must also be assessed.

NUTRIGENOMICS AS A TOOL IN THE PREVENTION OF LIPOTOXICITY: THE CASE OF SOY PROTEIN.

Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenomics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associated with lipotoxicity.

Nutrigenomics as a tool in the prevention of lipotoxicity: the case of soy protein

Abstract Obesity is associated with an increase of several metabolic disorders leading to the development of diseases such as type 2 diabetes and cardiovascular disease. This is due in part to the ectopic accumulation of triglycerides in organs that are non-adipose tissues, leading to lipotoxicity. Particularly, in the liver, the accumulation of lipids, mainly of triglycerides, leads to the formation of fatty liver. The accumulation of lipids in skeletal muscle and pancreas associates with insulin resistance and a decrease in insulin secretion, respectively. In addition, it has been suggested that dysbiosis of the gut microbiota can contribute to the process of lipid accumulation in non-adipose tissues, especially in the liver. The aim of the present review is to highlight the mechanisms associated with the development of lipotoxicity, and how with the advances in nutrigenomics, it is now possible to understand the molecular mechanisms by which some nutrients can attenuate the ectopic accumulation of triglycerides in non-adipose tissues. Particularly, we emphasize research conducted on the molecular mechanisms of action of soy protein and some of its isoflavones, and how these can reduce lipotoxicity by preventing the accumulation of lipids in the liver, skeletal muscle, and pancreas, as well as their role on the gut microbiota to attenuate the development of fatty liver. Thus, nutrigenomics is opening new dietary strategies based on several functional foods that can be used to ameliorate the pathologies associated with lipotoxicity.

Cardiac overexpression of perilipin 2 induces dynamic steatosis: prevention by hormone-sensitive lipase.

Cardiac intracellular lipid accumulation (steatosis) is a pathophysiological phenomenon observed in starvation and diabetes mellitus. Perilipin 2 (PLIN2) is a lipid droplet (LD)-associated protein expressed in nonadipose tissues, including the heart. To explore the pathophysiological function of myocardial PLIN2, we generated transgenic (Tg) mice by cardiac-specific overexpression of PLIN2. Tg hearts showed accumulation of numerous small LDs associated with mitochondrial chains and high cardiac triacylglycerol (TAG) content [8-fold greater than wild-type (WT) mice]. Despite massive steatosis, cardiac uptake of glucose, fatty acids and VLDL, systolic function, and expression of metabolic genes were comparable in the two genotypes, and no morphological changes were observed by electron microscopy in the Tg hearts. Twenty-four hours of fasting markedly reduced steatosis in Tg hearts, whereas WT mice showed accumulation of LDs. Although activity of adipose triglyceride lipase in heart homogenate was comparable between WT and Tg mice, activity of hormone-sensitive lipase (HSL) was 40-50% less in Tg than WT mice under both feeding and fasting conditions, suggesting interference of PLIN2 with HSL. Mice generated through crossing of PLIN2-Tg mice and HSL-Tg mice showed cardiac-specific HSL overexpression and complete lack of steatosis. The results suggest that cardiac PLIN2 plays an important pathophysiological role in the development of dynamic steatosis and that the latter was prevented by upregulation of intracellular lipases, including HSL.

UK lipohypertrophy interventional study.

INTRODUCTION: Lipohypertrophy (LH) is one of the most common complications of insulin therapy. We conducted a prospective study in 18 UK centres to assess the impact of a targeted LH intervention on a range of clinical, biological and socio-economic parameters. METHODS: Seventy-five insulin-injecting patients were recruited randomly and were followed prospectively for 3-6months, with results compared to baseline values. Interventions included the use of an intensive education program and a switch to a 4mm pen needle. RESULTS: At all injection sites LH decreased significantly by the end of the study, either disappearing completely or shrinking by approximately 50% from its original diameter. Injections into LH decreased by more than 75% by the end. Most patients were not correctly rotating injection sites at the beginning but by the end most were, by a 5-fold margin. Only 1/3 of our subjects used the 4mm needle at the beginning of the study, however, virtually all did by study end. The mean HbA1c improved by more than 4mmol/L and there were significantly lower levels of unexpected hypoglycaemia and glucose variability. Total daily doses of insulin dropped by an average of 5.6 IU by study end. CONCLUSIONS: We believe the impressive clinical improvements seen with training to prevent LH can be achieved by wide adoption of the interventions outlined in this study.

Grado de control lipídico en pacientes coronarios y medidas adoptadas por los médicos. Estudio REPAR / Degree of lipid control in patients with coronary heart disease and measures adopted by physicians. REPAR Study

Introducción y objetivos: El control lipídico es insuficiente en los pacientes coronarios, aunque las últimas guías de práctica clínica podrían haberlo modificado. El objetivo del estudio es analizar la consecución de los valores objetivo de colesterol unido a lipoproteínas de baja densidad, los factores asociados y las actitudes de los médicos ante un control deficiente. Métodos: Estudio observacional, prospectivo, multicéntrico y nacional de 1.103 pacientes con enfermedad coronaria estable, incluyendo determinaciones lipídicas y un amplio conjunto de variables clínicas. Estudio estadístico: modelo de regresión logística binaria con el procedimiento de eliminación secuencial progresiva paso a paso. Resultados: Solo el 26% de los pacientes tenían cifras de colesterol unido a lipoproteínas de baja densidad < 70 mg/dl pese a que el 95,3% recibía hipolipemiantes, el 45% de ellos de alta intensidad. Los factores independientes asociados a cifras < 70 mg/dl fueron la diabetes mellitus, el consumo de pan integral, las dislipemias de menor duración y, especialmente, el tratamiento de alta potencia. De los pacientes mal controlados, el médico solo aumentó el tratamiento al 26%. El principal factor asociado a escalada de tratamiento fue un tratamiento basal de baja potencia (odds ratio = 5,05; intervalo de confianza del 95%, 3,3-9,2). Tuvieron actitud más proactiva los médicos de más edad (p = 0,019) y más largo ejercicio (p = 0,02). Conclusiones: Pese a los cambios en las guías, solo un 26% de los pacientes coronarios presentan un adecuado control lipídico, y aun así en un 70% de los casos el médico mantiene el tratamiento pese a que, precisamente, es el tratamiento de alta intensidad el factor fundamental de un buen control (AU)

Introduction and objectives: Lipid control is insufficient in patients with coronary heart disease but this situation may be improving with the implementation of the latest clinical practice guidelines. The aim of this study was to analyze whether target values of low-density lipoprotein cholesterol are achieved and to identify associated factors and physicians’ attitudes to deficient control. Methods: We conducted a national, multicenter, prospective, observational study of 1103 patients with stable coronary heart disease, analyzing lipid values and a broad set of clinical variables. The statistical analysis involved a binary logistic regression model using backward stepwise elimination. Results: Low-density lipoprotein cholesterol was < 70 mg/dL in only 26% of patients, even though 95.3% were receiving cholesterol-lowering agents, 45% of which were high-intensity therapies. Independent predictors of low-density lipoprotein cholesterol < 70 mg/dL were diabetes mellitus, wholegrain bread, shorter history of dyslipidemia, and, especially, high-intensity cholesterol-lowering therapies. Physicians increased therapy in only 26% of poorly controlled patients. The main predictor of increased therapy was low-intensity baseline therapy (odds ratio = 5.05; 95% confidence interval, 3.3-9.2). A more proactive approach was observed in older physicians (P = .019) and longer physician practice (P = .02). Conclusions: Despite the new guidelines, only 26% of patients with coronary heart disease have adequate lipid control. In 70% of patients, physicians continue the same therapy, even though high-intensity cholesterol-lowering therapies are a key factor in good control (AU)

Reversal of Pathologic Lipid Accumulation in NPC1-Deficient Neurons by Drug-Promoted Release of LAMP1-Coated Lamellar Inclusions.

UNLABELLED: Aging and pathologic conditions cause intracellular aggregation of macromolecules and the dysfunction and degeneration of neurons, but the mechanisms are largely unknown. Prime examples are lysosomal storage disorders such as Niemann-Pick type C (NPC) disease, where defects in the endosomal-lysosomal protein NPC1 or NPC2 cause intracellular accumulation of unesterified cholesterol and other lipids leading to neurodegeneration and fatal neurovisceral symptoms. Here, we investigated the impact of NPC1 deficiency on rodent neurons using pharmacologic and genetic models of the disease. Improved ultrastructural detection of lipids and correlative light and electron microscopy identified lamellar inclusions as the subcellular site of cholesterol accumulation in neurons with impaired NPC1 activity. Immunogold labeling combined with transmission electron microscopy revealed the presence of CD63 on internal lamellae and of LAMP1 on the membrane surrounding the inclusions, indicating their origins from intraluminal vesicles of late endosomes and of a lysosomal compartment, respectively. Lamellar inclusions contained cell-intrinsic cholesterol and surface-labeled GM1, indicating the incorporation of plasma membrane components. Scanning electron microscopy revealed that the therapeutic drug candidate ß-cyclodextrin induces the subplasmalemmal location of lamellar inclusions and their subsequent release to the extracellular space. In parallel, ß-cyclodextrin mediated the NPC1-independent redistribution of cholesterol within neurons and thereby abolished a deleterious cycle of enhanced cholesterol synthesis and its intracellular accumulation, which was indicated by neuron-specific transcript analysis. Our study provides new mechanistic insight into the pathologic aggregation of macromolecules in neurons and suggests exocytosis as cellular target for its therapeutic reversal. SIGNIFICANCE STATEMENT: Many neurodegenerative diseases involve pathologic accumulation of molecules within neurons, but the subcellular location and the cellular impact are often unknown and therapeutic approaches lacking. We investigated these questions in the lysosomal storage disorder Niemann-Pick type C (NPC), where a defect in intracellular cholesterol transport causes loss of neurons and fatal neurovisceral symptoms. Here, we identify lamellar inclusions as the subcellular site of lipid accumulation in neurons, we uncover a vicious cycle of cholesterol synthesis and accretion, which may cause gradual neurodegeneration, and we reveal how ß-cyclodextrin, a potential therapeutic drug, reverts these changes. Our study provides new mechanistic insight in NPC disease and uncovers new targets for therapeutic approaches.

Risk factors of lipid metabolism disorders in residents of multi-environmental exposure to cadmium and arsenic.

The authors evaluated negative effects of cadmium and arsenic compounds on health of population residing near storage of extraction and processing waste of ore mining and processing enterprise. Hygienic analysis covered quality of ambient air, drinkable water and foods, evaluation of risk factors of lipid metabolism disorders. Clinical and laboratory examination involved 137 children and 99 adults in chronic multi-environmental (ambient air, water, foods) exposure to metals (cadmium and arsenic, HI 1.21-1.29), diagnosed endocrine diseases including lipid metabolism disorders (excessive nutrition and obesity, E67.8-66.0) in adults 1.4 times more, and in children in 1.7-2.2 times more than in the reference group. Direct probable statistically significant cause-effect relationship was established between lipid metabolism disorders and serum levels of cadmium and arsenic (R² = 0,36-0,95; 71,07≤ F ≤2597,94; p< 0,001). In multi-environmental exposure to cadmium and arsenic, reduced index of lipid metabolic disorders risk in adult population exceeds upper limit of low risk level (0,05) at 33 years of age, of high risk level (0,35) - at 58 years of age and very high (0,6) - at 63 years of age.

Adaptación española de las Guías Europeas de 2016 sobre prevención de la enfermedad cardiovascular en la práctica clínica / Spanish adaptation of the 2016 European Guidelines on cardiovascular disease revention in clinical practice

Las VI Guías Europeas de Prevención Cardiovascular recomiendan combinar las estrategias poblacionales y de alto riesgo, con los cambios de estilo de vida como piedra angular de la prevención, y proponen la función SCORE para cuantificar el riesgo cardiovascular. Esta guía hace más hincapié en las intervenciones específicas de las enfermedades y las condiciones propias de las mujeres, las personas jóvenes y las minorías étnicas. No se recomienda el cribado de aterosclerosis subclínica con técnicas de imagen no invasivas. La guía establece cuatro niveles de riesgo (muy alto, alto, moderado y bajo), con objetivos terapéuticos de control lipídico según el riesgo. La diabetes mellitus confiere un riesgo alto, excepto en sujetos con diabetes tipo 2 con menos de 10 años de evolución, sin otros factores de riesgo ni complicaciones, o con diabetes tipo 1 de corta evolución sin complicaciones. La decisión de iniciar el tratamiento farmacológico de la hipertensión arterial dependerá del nivel de presión arterial y del riesgo cardiovascular, teniendo en cuenta la lesión de órganos diana. Siguen sin recomendarse los fármacos antiplaquetarios en prevención primaria por el riesgo de sangrado. La baja adherencia al tratamiento exige simplificar el régimen terapéutico e identificar y combatir sus causas. La guía destaca que los profesionales de la salud pueden ejercer un papel importante en la promoción de intervenciones poblacionales y propone medidas eficaces, tanto a nivel individual como poblacional, para promover una dieta saludable, la práctica de actividad física, el abandono del tabaquismo y la protección contra el abuso de alcohol (AU)

The VI European Guidelines for Cardiovascular Prevention recommend combining population and high-risk strategies with lifestyle changes as a cornerstone of prevention, and propose the SCORE function to quantify cardiovascular risk. The guidelines highlight disease specific interventions, and conditions as women, young people and ethnic minorities. Screening for subclinical atherosclerosis with noninvasive imaging techniques is not recommended. The guidelines distinguish four risk levels (very high, high, moderate and low) with therapeutic objectives for lipid control according to risk. Diabetes mellitus confers a high risk, except for subjects with type 2 diabetes with less than 10 years of evolution, without other risk factors or complications, or type 1 diabetes of short evolution without complications. The decision to start pharmacological treatment of arterial hypertension will depend on the blood pressure level and the cardiovascular risk, taking into account the lesion of target organs. The guidelines don’t recommend antiplatelet drugs in primary prevention because of the increased bleeding risk. The low adherence to the medication requires simplified therapeutic regimes and to identify and combat its causes. The guidelines highlight the responsibility of health professionals to take an active role in advocating evidence-based interventions at the population level, and propose effective interventions, at individual and population level, to promote a healthy diet, the practice of physical activity, the cessation of smoking and the protection against alcohol abuse (AU)

Cambios en el control metabólico de los pacientes diabéticos tipo 2 de un centro de salud / Changes in the metabolic control of type 2 diabetic patients in a health center

Objetivo: Conocer los cambios producidos en un período de cuatro años en el control de los pacientes diabéticos y en el uso de la medicación en la práctica habitual. Diseño del estudio: Estudio descriptivo, observacional, transversal. Emplazamiento: Zona de Salud Manzanares II (Manzanares - Ciudad Real - España). Participantes: Pacientes diabéticos de ambos sexos de la Zona de Salud. Mediciones principales: Se recogieron datos sociodemográficos, factores de riesgo cardiovascular, repercusión macro y microvascular de la diabetes, valores analíticos (glucídicos, lipídicos) y tensionales, así como los fármacos empleados en el tratamiento de diabetes, dislipemia y con efecto antiagregante/anticoagulante. Los datos fueron comparados con los del estudio observacional realizado en 2010. Resultados: El control metabólico (HbA1c) ha mejorado en 2014: 7,09% (DE: 1,17) respecto a 2010: 7,22% (DE: 1,21), siendo significativo en el porcentaje de valores más elevados de HbA1c (≥8% y ≥10%). El porcentaje de HbA1c ≤7% ha pasado del 50,5% al 53,7%. Los mayores descensos se han producido en los parámetros lipídicos: colesterol total (p<0,001), LDL-colesterol (p<0,001) y microalbuminuria (p<0,01). El porcentaje de HbA1c ≤7% y LDL-colesterol ≤100 mg/dl ha pasado del 13,1% al 21,7% (p<0,01). Ha disminuido el uso de sulfonilureas (p<0,01) y aumentado el de IDDP-4 (p<0,001), estatinas (p<0,05) y de ácido acetilsalicílico (p<0,01). Conclusiones: En el periodo de cuatro años ha mejorado el control metabólico glucídico, siendo significativo el cambio en el patrón lipídico. Ha disminuido el uso de sulfonilureas y ha aumentado el uso de IDPP-4, estatinas y ácido acetilsalicílico (AU)

Objective: To know the changes achieved in a period of four years in the control of diabetic patients, and the changes in the use of medication in routine practice. Study design: Cross-sectional descriptive study. Setting: Primary Care Centre of Manzanares II (Manzanares - Ciudad Real - Spain). Participants: Diabetic patients of both sexes in the Health Zone. Measurements: Sociodemographic data, cardiovascular risk factors, macro and microvascular impact of diabetes, blood pressure and analytical parameters (glucidic, lipidic), as well as drugs used in the treatment of diabetes and dyslipidemia, and antiplatelet/anticoagulant drugs were collected. These data were compared with those of the cross-sectional descriptive study conducted in 2010. Results: The metabolic control (HbA1C) has improved in 2014: 7.09 % (SD:1.17) with regard to 2010: 7.22 % (SD: 1.21), being significant in the percentage of higher values of HbA1C (≥8 % and ≥10 %). The percentage of HbA1C ≤7 % has increased from 50.5 % to 53.7 %. The largest decreases have occurred in the lipid parameters: total cholesterol (p<0.001), LDL-cholesterol (p <0.001)) and microalbuminuria (p <0.01). The percentage of HbA1C ≤7 % and LDL-cholesterol ≤100 mg/dl has increased from 13.1 % to 21.7 % (p <0,01). The use of sulfonylureas has decreased (p <0.01) and those of IDDP-4 (p <0.001), statins (p <0.05) and acetyilsalicylic acid (p <0.01) have increased. Conclusions: The carbohydrate metabolic control has improved during a period of four years, with significant changes in lipid parameters. The use of sulfonylureas has decreased, and the use of IDPP-4, statins and acetylsalicylic acid has increased (AU)

Angelica sinensis polysaccharide regulates glucose and lipid metabolism disorder in prediabetic and streptozotocin-induced diabetic mice through the elevation of glycogen levels and reduction of inflammatory factors.

The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-α in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes.

L-Carnitine intake prevents irregular feeding-induced obesity and lipid metabolism disorder.

L-Carnitine supplementation has been used to reduce obesity caused by high-fat diet, which is beneficial for lowering blood and hepatic lipid levels, and for ameliorating fatty liver. However, whether l-carnitine may affect irregular feeding-induced obesity and lipid metabolism disorder is still largely unknown. In the present study, we developed a time-delayed pattern of eating, and investigated the effects of l-carnitine on the irregular eating induced adiposity in mice. After an experimental period of 8 weeks with l-carnitine supplementation, l-carnitine significantly inhibited body weight increase and epididymal fat weight gain induced by the time-delayed feeding. In addition, l-carnitine administration decreased levels of serum alanine aminotransferase (GPT), glutamic oxalacetic transaminase (GOT) and triglyceride (TG), which were significantly elevated by the irregular feeding. Moreover, mice supplemented with l-carnitine did not display glucose intolerance-associated hallmarks, which were found in the irregular feeding-induced obesity. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that l-carnitine counteracted the negative alterations of lipid metabolic gene expression (fatty acid synthase, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, cholesterol 7α-hydroxylase, carnitine/acylcarnitine translocase) in the liver and fat of mice caused by the irregular feeding. Therefore, our results suggest that the time-delayed pattern of eating can induce adiposity and lipid metabolic disorders, while l-carnitine supplementation might prevent these negative symptoms.

Hiperlipidemia familiar combinada: documento de consenso / Familial combined hyperlipidemia: consensus document

La hiperlipidemia familiar combinada (HFC) es un trastorno muy frecuente asociado a enfermedad coronaria prematura. Se transmite de forma autosómica dominante, aunque no existe un gen único asociado al trastorno. El diagnóstico se realiza mediante criterios clínicos, y son importantes la variabilidad del fenotipo lipídico y la historia familiar de hiperlipidemia. Es frecuente la asociación con diabetes mellitus tipo 2, hipertensión arterial y obesidad central. Los pacientes con HFC se consideran de riesgo cardiovascular alto y el objetivo terapéutico es un colesterol-LDL < 100 mg/dl, y < 70 mg/dl en presencia de enfermedad cardiovascular establecida o diabetes mellitus. Los pacientes con HFC requieren tratamiento con estatinas potentes y, a veces, tratamiento combinado. La identificación y el manejo de otros factores de riesgo cardiovascular, como la diabetes y la hipertensión, son fundamentales para reducir la carga de enfermedad cardiovascular. Este documento proporciona recomendaciones para el diagnóstico y el tratamiento integral de los pacientes con HFC especialmente dirigidas a médicos de atención primaria (AU)

Familial combined hyperlipidemia (FCH) is a frequent disorder associated with premature coronary artery disease. It is transmitted in an autosomal dominant manner, although there is not a unique gene involved. The diagnosis is performed using clinical criteria, and variability in lipid phenotype and family history of hyperlipidemia are necessaries. Frequently, the disorder is associated with type 2 diabetes mellitus, arterial hypertension and central obesity. Patients with FCH are considered as high cardiovascular risk and the lipid target is an LDL-cholesterol < 100 mg/dL, and < 70 mg/dL if cardiovascular disease or type 2 diabetes are present. Patients with FCH require lipid lowering treatment using potent statins and sometimes, combined lipid-lowering treatment. Identification and management of other cardiovascular risk factors as type 2 diabetes and hypertension are fundamental to reduce cardiovascular disease burden. This document gives recommendations for the diagnosis and global treatment of patients with FCH directed to specialists and general practitioners (AU)

Role of the sex hormone estrogen in the prevention of lipid disorder.

Natural selection clearly favors the accumulation and storage of lipids in humans, predisposing women to store excess fat in gluteal regions and predisposing males to store excess fat in visceral regions. In addition, gender differences are reported with respect to the concentrations of circulating lipids and lipoproteins, with lower concentrations of total cholesterol and low density lipoprotein (LDL)-cholesterol in premenopausal women than in men. This latter evidence renders gender differences in fat distribution and whole-body lipid metabolism of particular interest with respect to the incidence and prevalence of human diseases. Although the mechanisms underlying gender-related differences in body fat distribution and lipid homeostasis remain to be fully determined, the reported differences appear to principally reflect the actions of the sex steroid hormone estrogen on whole-body lipid metabolism. In the present review, we dissect the role played by 17ß-estradiol, the most active between estrogens, and by its receptors in regulating lipid homeostasis in adipose tissue, liver, and brain, evaluating the potential impact of this hormone in preventing lipid abnormalities.

Green tea extract containing a highly absorbent catechin prevents diet-induced lipid metabolism disorder.

We investigated the effects of extracts of Benifuuki (a tea cultivar that contains methylated catechins such as epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me)) in mice fed a high-fat/high-sucrose (HF/HS) diet. This tea cultivar was then compared with an extract of Yabukita (a popular tea cultivar that lacks methylated catechins). For 6 weeks, C57BL/6J mice were fed either HF/HS diet with or without tea extracts from tea cultivars, which contained almost identical ingredients except for methylated catechins (i.e., Yabukita (0.2% and 1%) or Benifuuki (0.2% and 1%) extract powders). Supplementation with Benifuuki 0.2% markedly lowered plasma levels of TG and NEFAs compared with mice supplemented with Yabukita 0.2%. The diet containing Benifuuki 1% decreased adipose tissue weights, liver TG, and expression of lipogenic genes in the liver. These results suggested that Benifuuki had much greater lipid-lowering effects than Yabukita. Taken together, these data suggest that methylated catechins direct the strong lipid-lowering activity of Benifuuki.

Resveratrol prevents global cerebral ischemia-induced decrease in lipid content.

OBJECTIVE: The present study was undertaken to evaluate whether resveratrol (RSV) modulates membrane lipid composition, as well as on ganglioside profile in ischemia/reperfusion injury. METHODS: Global cerebral ischemia was induced by four-vessel occlusion for 10 minutes. RSV (30 mg/kg) or vehicle was intraperitoneally administered to rats 7 days prior to ischemia. Brain structures were homogenized with chloroform/methanol for ganglioside, phospholipids, and cholesterol levels. RESULTS: RSV significantly prevented the reduction in the total content of gangliosides, phospholipids, and cholesterol in hippocampi and cerebral cortex induced by global cerebral ischemia. Although ischemia/reperfusion decreased ganglioside content, the ganglioside profiles were apparently not modified. CONCLUSIONS: Our experiments suggest that lipid metabolism is important for development of ischemic damage and indicate that RSV treatment 7 days prior to ischemia may prevent membrane lipid loss.

Insulin sensitization with a peroxisome proliferator-activated receptor γ agonist prevents adrenocortical lipid infiltration and secretory changes induced by a high-sucrose diet.

It has been hypothesized that deviations in glucocorticoid secretion and/or action may contribute to somatic and biochemical changes observed in patients with and animal models of insulin resistance (IR). In this study, we analyzed changes in rat adrenocortical function and morphology associated with the development of IR, generated in male adult rats by the addition of 30% sucrose to the drinking water. Caloric intake, body and adipose tissue weights, and biochemical parameters associated with IR were determined. Expression levels of Star, Cyp11A1, Mc2r, Pparγ (Pparg), and Cd36 were evaluated by real-time PCR, histochemical analysis of the adrenal cortex was performed using Masson's trichrome and Sudan III staining, and corticosterone levels were measured by RIA. After 7 weeks of sucrose administration, higher serum glucose, insulin, and triglyceride levels and an altered glycemic response to an i.p. insulin test were detected. Adrenal glands showed a neutral lipid infiltration. An increase in Star, Cyp11A1, Mc2r, Pparg and Cd36 and a decrease in Mc2r levels were also found. Furthermore, sucrose-treated animals exhibited higher basal corticosterone levels and a blunted response to ACTH injection. Noteworthy, the adrenocortical (functional and histological) abnormalities were prevented in sucrose-treated rats by the simultaneous administration of an insulin-sensitizing PPARγ agonist. In conclusion, sucrose-induced IR affects adrenocortical morphology and function possibly via the generation of adipokines or lipid metabolites within the adrenal gland. These abnormalities are prevented by the administration of a PPARγ agonist by mechanisms involving both extra- and intra-adrenal effects.

The rise of cholesterol testing: how much is unnecessary.

BACKGROUND: Laboratory testing has increased dramatically over recent decades, which is a consequence particularly of repeat testing or monitoring, as either a response to treatment or follow-up. AIM: To assess rates of measurement of lipid levels (total cholesterol, high-density lipoprotein, triglyceride) for diagnosis and monitoring over the last 20 years. DESIGN OF STUDY: Audit of electronic database. SETTING: A single region in the UK (Oxfordshire). METHOD: Specimens from individual patients were matched over time. All tests that were the third or more in a 3-year period were considered to be for monitoring, while the first and second were considered to be for diagnosis. As recent evidence-based recommendations suggest that frequent monitoring of cholesterol may reflect measurement error rather than true changes, between one and three tests in each 3-year period were considered to be 'necessary'. RESULTS: Over the 20 years from 1987 there has been a more than 15-fold rise in the overall number of lipid tests requested. After a small decline in the early 1990s, testing rose steadily after publication of several large statin trials, particularly tests requested in primary rather than secondary care. Repeat testing (likely to be for monitoring) rose from 24% of tests (1993-1995) to 61% (2005-2007), with between 42% and 79% of tests in 2005-2007 possibly being unnecessary. Mean cholesterol values declined over time from 1996 onwards. CONCLUSION: In the last decade, the number of cholesterol tests performed in Oxfordshire has risen dramatically. Much of this appears to be for monitoring purposes rather than case finding or risk assessment. The majority of cholesterol tests requested may be unnecessary.