Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? / O Produto de Acumulação Lipídica está Associado a um Perfil Aterogênico de Lipoproteínas em Indivíduos Brasileiros?

Abstract Background: Lipid accumulation product (LAP), a simple and low-cost tool, is a novel biomarker of central lipid accumulation and represents a potential surrogate marker for atherogenic lipoprotein profile. However, its association with lipoprotein subfractions has not been described in the literature. Objective: To determine whether LAP index could be used as a marker of low- and high-density lipoprotein (LDL and HDL) size in Brazilian individuals. Methods: This cross-sectional study included patients (n = 351) of both sexes and age between 30-74 years. Clinical and sociodemographic data and family history of diseases were evaluated. Lipoprotein size, and levels of total cholesterol (TC), lipoproteins, apolipoprotein AI and B (APO AI/APO B), glucose, insulin, insulin resistance index (HOMA-IR) and non-esterified fatty acids (NEFA) were assessed in blood samples. LAP was calculated by the formulas [(waist circumference[cm]-58) × (triglycerides[mmol/L]) for women and (waist circumference [cm]-65) × (triglycerides [mmol/L]) for men]. The association between LAP and metabolic parameters were tested by linear trend (general linear model, GLM test) before and after multiple adjustments for potential confounders (sex, age, smoking, statin, fibrate, and hypoglycemic drugs) at significant level p < 0.05. Results: LAP was positively associated with TC, APO B, NEFA, glucose, insulin and HOMA-IR values, and negatively associated with HDL-C. Higher central lipid accumulation was corelated with higher percentage of intermediate HDL and of small LDL and HDL and less amount of large HDL. LDL size was also reduced in greater LAP index values. The negative impact of LAP was maintained after adjustment for multiple variables. Conclusion: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.

Resumo Fundamento: O produto de acumulação lipídica (LAP), um instrumento simples e de baixo custo, é um novo biomarcador de acúmulo de gordura central e representa um marcador substituto potencial para o perfil aterogênico de lipoproteínas. No entanto, sua associação com subfrações de lipoproteínas ainda não foi descrita na literatura. Objetivo: Determinar se o LAP pode ser usado como um marcador de tamanho da lipoproteína de baixa densidade (LDL) e de alta densidade (HDL) em indivíduos brasileiros. Métodos: Este estudo transversal incluiu 351 pacientes de ambos os sexos e idade entre 30 e 74 anos. Dados clínicos e sociodemográficos e história familiar de doenças foram avaliados. O tamanho das lipoproteínas, e níveis de colesterol total (CT), lipoproteínas, apolipoproteína AI e B (APO AI/APO B), glicose, ácidos graxos não esterificados (AGNEs) e insulina, e índice de resistência insulínica (HOMA-IR) foram avaliados em amostras de sangue. O LAP foi calculado utilizando-se as fórmulas (circunferência da cintura (cm]-58) × (triglicerídeos[mmol/L]) para mulheres e (circunferência da cintura[cm]-65) × (triglicerídeos [mmol/L]) para homens. Associações entre LAP e parâmetros metabólicos foram testadas por tendência linear (modelo linear generalizado, GLM) antes e após ajustes por fatores de confusão (sexo, idade, tabagismo, uso de estatinas, fibratos e hipoglicemiantes) ao nível de significância de p < 0,05). Resultados: LAP apresentou uma associação positiva com CT, APO B, AGNEs, glicose, insulina, HOMA-IR, e uma associação negativa com HDL-C. Maior acúmulo de gordura central correlacionou-se com maior porcentagem de HDL intermediária e de partículas pequenas de LDL e HDL, e menor porcentagem de HDL grande. O tamanho da LDL também era reduzido em valores de LAP mais elevados. O impacto negativo do LAP foi mantido após ajuste para múltiplas variáveis. Conclusão: o LAP esteve fortemente associado com o perfil aterogênico de subfrações de lipoproteínas, independetemente dos fatores de confusão.

Classification of different degrees of adiposity in sedentary rats

In experimental studies, several parameters, such as body weight, body mass index, adiposity index, and dual-energy X-ray absorptiometry, have commonly been used to demonstrate increased adiposity and investigate the mechanisms underlying obesity and sedentary lifestyles. However, these investigations have not classified the degree of adiposity nor defined adiposity categories for rats, such as normal, overweight, and obese. The aim of the study was to characterize the degree of adiposity in rats fed a high-fat diet using cluster analysis and to create adiposity intervals in an experimental model of obesity. Thirty-day-old male Wistar rats were fed a normal (n=41) or a high-fat (n=43) diet for 15 weeks. Obesity was defined based on the adiposity index; and the degree of adiposity was evaluated using cluster analysis. Cluster analysis allowed the rats to be classified into two groups (overweight and obese). The obese group displayed significantly higher total body fat and a higher adiposity index compared with those of the overweight group. No differences in systolic blood pressure or nonesterified fatty acid, glucose, total cholesterol, or triglyceride levels were observed between the obese and overweight groups. The adiposity index of the obese group was positively correlated with final body weight, total body fat, and leptin levels. Despite the classification of sedentary rats into overweight and obese groups, it was not possible to identify differences in the comorbidities between the two groups.

Perfil de ácidos grasos libres (AGL) en suero de jóvenes colombianos con obesidad y síndrome metabólico / Profile of free fatty acids (FFA) in serum of young Colombians with obesity and metabolic syndrome

La obesidad se relaciona con mayor concentración de ácidos grasos libres (AGL) circulantes. En adultos obesos el perfil de AGL difiere comparado con individuos de peso adecuado, en adolescentes los resultados son contradictorios. El objetivo fue comparar el perfil de AGL de jóvenes obesos con y sin Síndrome Metabólico (SM) y explorar la asociación entre estos AGL con las alteraciones metabólicas propias de la obesidad y el SM. Estudio transversal, con 96 jóvenes entre 10 y 18 años divididos en 3 grupos: 1) obesos con SM, 2) obesos sin SM y 3) peso adecuado (PA), pareados uno a uno por edad, sexo, maduración puberal y estrato socioeconómico. El estado nutricional se clasificó según el índice de masa corporal (IMC) en obesos (IMC>p98) y Peso Adecuado (PA) (IMC p15-p85) según OMS/2007, se evaluó circunferencia de cintura, adiposidad, perfil lipídico, proteína C reactiva ultra sensible (PCRhs), glucemia, insulina y resistencia a la insulina (RI) según homeostatic model assessment (HOMA). La concentración sérica de AGL se determinó mediante cromatografía gaseosa. Ambos grupos de obesos presentaron mayor adiposidad, inflamación, AGL totales y frecuencia de palmitoléico-16:1n7 comparados con PA. Los obesos con SM presentaron más alteraciones metabólicas, mayor cantidad de dihomo-γ-linolénico (DHGL- 20:3n6) y relación 20:3n6/18:2n6 indicativa de mayor actividad de Δ6 desaturasa (D6D). Los AGL totales, palmitoléico- 16:1n7, DHGL-20:3n6, actividad D6D y PCRhs correlacionaron significativamente con variables de adiposidad, RI y triglicéridos. Los resultados en obesos con SM permiten asociar la obesidad central con inflamación, lipolisis aumentada en el tejido adiposo visceral y alteraciones metabólicas.

Obesity produces greater circulation of free fatty acids (FFA). In adults, the FFA composition changes in states of obesity; in adolescents, the results are contradictory. This study compare the FFA profile of obese youth with and without Metabolic Syndrome (MetS) and explore the association between FFA and metabolic alterations of obesity and MetS. A cross-sectional study with 96 young people between 10 and 18 years old was divided into three groups: 1) obese youth with MetS, 2) obese youth without MetS; and 3) adequate weight (AW), matched according to age, gender, pubertal maturation and socioeconomic stratum. The nutritional status was classified according to the body-mass index (BMI), according to the World Health Organization 2007 (WHO, 2007); the waist circumference (WC), adiposity, lipid profile, highly-sensitive reactive C protein (hsRCP), glucose, insulin and insulin resistance (IR), according to the homeostatic model assessment (HOMA Calculator Version 2.2.2). The FFA serum concentration was determined by gas chromatography. Both obese groups had higher adiposity, inflamation (hsRCP), FFA totals and frequency palmitoleic-16:In7, compared to AW. The obese with MetS presented more metabolic alterations, a greater amount of dihomo-γ-linolenic (DHGL-20:3n6) and a 20:3n6/18:2n6 relation, indicative of increased activity of Δ6 desaturase (D6D). The FFA totals, palmitoleic-16:1n7, DHGL-20:3n6, D6D activity and hsRCP significantly correlated with variables of adiposity, IR and triglicerides. The results in obese with MetS corroborate the association among central obesity, inflammation and increased lipolysis in visceral adipose tissue and metabolic alterations.

Perfil lipídico en mujeres embarazadas sanas de tres regiones de Chile / Lipid profile in healthy pregnant women in three regions of Chile

Antecedentes: Los lípidos plasmáticos maternos durante el embarazo pueden influir en el crecimiento fetal, particularmente en pacientes con diabetes gestacional; estos lípidos cambian su concentración plasmática materna a lo largo de la gestación. Objetivo: Calcular tablas y curvas de lípidos normales según edad gestacional en una población de embarazadas chilenas. Método: Se midió el colesterol total (CT), colesterol LDL (LDL-C) triglicéridos (TG), Colesterol-HDL (HDL-C), y ácidos grasos no esterificados (NEFA), en 94 embarazadas sanas y jóvenes (<33 años, edad media de 27,6 +/- 6,2 años), con peso pregestacional normal (Índice de Masa Corporal entre 20 y 24,9 Kg/m2 y medio de 23,3 +/- 2,0 Kg/m2). Las pacientes provenían de: Hospital Parroquial de San Bernardo, Santiago (n=55), Hospital de Talca (n=2); Hospital del Profesor, Santiago (n=18); Hospital Regional de Concepción (n=9) y Hospital Clínico de la Pontificia Universidad Católica de Chile (n=10). Resultados: Calculamos, para cada uno de los cuatro lípidos, las curvas de percentil 50, percentil 90 y percentil 10, en mg/dL y mmol/l. Los NEFA solo fueron expresados en mmol/l. Incluimos las funciones matemáticas de las curvas de regresión polinomial de los cuatro lípidos con el fin que sean fácilmente reproducibles en otros tamaños. Conclusiones: Calculamos las tablas y curvas de lípidos maternos normales a lo largo del embarazo, que sean aplicables a la población de embarazadas chilenas.

Background: In normal human pregnancy, maternal lipids can modify the rate of fetal growth, particularly in pregnancies with Gestational Diabetes Mellitus (GDM). These lipids change continuously their serum concentration in the mother along the pregnancy. Aim: To calculate tables and curves of normal serum lipids, according to gestational age, in healthy Chilean pregnant women. Methods: We measured total cholesterol (CT), LDL-cholesterol (LDL-C), triglycerides (TG), HDL-Cholesterol (HDL-C), and Non-Esterified Fatty Acids (NEFA) in 94 young and healthy pregnant women (< 33 years, mean age 27.6 +/- 6.2 years), with normal pregestational Body Mass Index (BMI, 20.0-24.9 Kg/m2 , mean value= 23.3 +/- 2.0 Kg/m2). The women of the study were patients of 5 hospitals: Hospital Parroquial de San Bernardo, Santiago (n=55), Hospital de Talca (n=2); Hospital del Profesor, Santiago (n=18); Hospital Regional de Concepción (n=9) and Hospital Clínico de la Pontificia Universidad Católica de Chile (n=10). Results: For each one of the lipids, we calculated curves of 50th, 90th and 10th percentiles, both in mg/dL and mmol/L (the NEFA were expressed only in mmol/L). The mathematical functions of the curves of polynomial regression of all lipids were included in the manuscript, in order to facilitate their reproduction. Conclusions: We calculated tables and curves of normal maternal serum lipids in relation to gestational, in order to make these available for use in the care of Chilean pregnant women.

Obesity does not Lead to Imbalance Between Myocardial Phospholamban Phosphorylation and Dephosphorylation / Obesidade não Acarreta Desequilíbrio entre Fosforilação e Desfosforilação da Fosfolambam Miocárdica

Background: The activation of the beta-adrenergic system promotes G protein stimulation that, via cyclic adenosine monophosphate (cAMP), alters the structure of protein kinase A (PKA) and leads to phospholamban (PLB) phosphorylation. This protein participates in the system that controls intracellular calcium in muscle cells, and it is the primary regulator of sarcoplasmic reticulum calcium pump activity. In obesity, the beta-adrenergic system is activated by the influence of increased leptin, therefore, resulting in higher myocardial phospholamban phosphorylation via cAMP-PKA. Objective: To investigate the involvement of proteins which regulate the degree of PLB phosphorylation due to beta-adrenergic activation in obesity. In the present study, we hypothesized that there is an imbalance between phospholamban phosphorylation and dephosphorylation, with prevalence of protein phosphorylation. Methods: Male Wistar rats were randomly distributed into two groups: control (n = 14), fed with normocaloric diet; and obese (n = 13), fed with a cycle of four unsaturated high-fat diets. Obesity was determined by the adiposity index, and protein expressions of phosphatase 1 (PP-1), PKA, PLB, phosphorylated phospholamban at serine16 (PPLB-Ser16) were assessed by Western blot. Results: Obesity caused glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hyperleptinemia and did not alter the protein expression of PKA, PP-1, PLB, PPLB-Ser16. Conclusion: Obesity does not promote an imbalance between myocardial PLB phosphorylation and dephosphorylation via beta-adrenergic system. .

Fundamento: A ativação do sistema beta-adrenérgico promove a estimulação da proteína G, que, via adenosina monofosfato cíclico (AMPc), altera a estrutura da proteina quinase A (PKA) e acarreta a fosforilação da fosfolambam (PLB). Essa proteína participa do sistema envolvido no controle de cálcio intracelular, em células musculares, sendo a principal reguladora da atividade da bomba de cálcio do retículo sarcoplasmático. Na obesidade ocorre ativação do sistema beta-adrenérgico por influência do aumento da leptina, acarretando, consequentemente, maior fosforilação da fosfolambam miocárdica, via AMPc-PKA. Objetivo: Investigar, na obesidade, o envolvimento das proteínas que regulam o grau de fosforilação do PLB decorrente da ativação beta-adrenérgica. A hipótese do estudo é que há desequilíbrio entre a fosforilação e a desfosforilação da fosfolambam, com predomínio da fosforilação da proteína. Métodos: Ratos Wistar machos foram randomizados e distribuídos em dois grupos: controle (n = 14), alimentado com dieta normocalórica, e obeso (n = 13), com um ciclo de quatro dietas hiperlipídicas insaturadas. A obesidade foi determinada pelo índice de adiposidade, e as expressões proteicas de fosfatase 1 (PP-1), PKA, PLB, fosfolambam fosforilado na serina 16 (pPLB-ser16) foram realizadas por Western Blot. Resultados: A obesidade acarretou intolerância à glicose, hiperinsulinemia, hipertrigliceridemia, hiperleptinemia e não alterou a expressão proteica de PKA, PP-1, PLB, pPLB-ser16. Conclusão: A obesidade não promove desequilíbrio entre a fosforilação e a desfosforilação, via beta-adrenérgica, do PLB miocárdico. .

Effects of supplementation with omega-3 on insulin sensitivity and non-esterified free fatty acid (NEFA) in type 2 diabetic patients / Efeito da suplementação com ômega-3 sobre a sensibilidade à insulina e aos ácidos graxos livres não esterificados (AGNE) em pacientes com diabetes tipo 2

Objective: The aim of this study was to determine the role of omega-3 supplementation on NEFA concentration, insulin sensitivity and resistance, and glucose and lipid metabolism in type 2 diabetic patients. Subjects and methods: Forty-four type 2 diabetic patients were randomly recruited into two groups. Group A received 4 g/day omega-3 soft gels, and group B received a placebo for 10 wks. Blood samples were collected after 12-h fast. Physical activity records, three-day food records, and anthropometric measurements were obtained from all participants at the beginning and end of the study. Results: Omega-3 supplementation caused a significant reduction in NEFA in the intervention group compared with the placebo group (P = 0.009). Additionally, the administration of omega-3 resulted in significantly greater changes (Diff) for the intervention group in various parameters, such as insulin and Quicki indices compared with the placebo group (P < 0.05). Conclusions: Omega-3 fatty acid supplementation in type 2 diabetic patients improved insulin sensitivity, probably due to the decrease in NEFA concentrations. Arq Bras Endocrinol Metab. 2014;58(4):335-40 .

Objetivo: O objetivo deste estudo foi analisar o papel da suplementação com ácidos graxos ômega-3 sobre a concentração de ácidos graxos não esterificados (AGNE), resistência e sensibilidade à insulina e metabolismo de lipídios em pacientes com diabetes melito tipo 2. Sujeitos e métodos: Quarenta e quatro pacientes com diabetes tipo 2 foram recrutados aleatoriamente e alocados em um de dois grupos. O Grupo A recebeu 4 g/dia de ômega-3 na forma de cápsulas gelatinosas e o grupo B recebeu placebo durante 10 semanas. Amostras de sangue foram coletadas após 12 horas de jejum. Registros da atividade física, da dieta de três dias e medidas antropométricas foram obtidos de todos os participantes no início e no final do estudo. Resultados: A suplementação com ômega-3 causou uma redução significativa na AGNE em comparação com grupo placebo (P = 0,008). Além disso, a administração de ômega-3 resultou em alterações significativamente maiores (Dif) em vários parâmetros, tais como a insulina, HOMA-IR e QUICKI, comparando com placebo (P < 0,05). Conclusões: A suplementação com ácidos graxos ômega-3 em pacientes diabéticos tipo 2 melhorou a sensibilidade à insulina, provavelmente devido à diminuição da concentração de AGNE. Arq Bras Endocrinol Metab. 2014;58(4):335-40 .

Relationship among blood indicators of lipomobilization and hepatic function during early lactation in high-yielding dairy cows

Blood indicators are used as a tool to diagnose metabolic disorders. The present work was conducted to study the relationships among blood indicators of lipomobilization and hepatic function in high-yielding dairy cows. Two groups of Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows from four different herds with similar husbandry characteristics in Galicia, Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had higher levels of BHB and NEFA than mid lactation cows. High lipomobilization (NEFA > 400 micromol/L) was detected in 67% and 7% of early lactation and mid lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was detected in 41% and 28% of the early lactation and lactation cows, respectively. TG concentrations were low in all cows suffering subclinical ketosis and in 61% of the cows with high lipomobilization. During early lactation, 30% of cows suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic function was observed in early lactation cows as shown by lower concentrations of glucose, total protein, and urea.

Effect of Aspirin on the Expression of Hepatocyte NF-kappaB and Serum TNF-alpha in Streptozotocin-Induced Type 2 Diabetic Rats

Aspirin is a kind of anti-inflammatory drug and may be used to reverse hyperglycemia, hyperinsulinemia, and dyslipidemia by improving insulin resistance. We hypothesized that aspirin improves insulin resistance in type 2 diabetes by inhibiting hepatic nuclear factor kappa-beta (NF-kappaB) activation and serum tumor necrosis factor-alpha (TNF-alpha). Adult male Wistar rats were randomly divided into four groups: control, untreated diabetic, diabetic treated with metformin (100 mg/kg/day), and diabetic treated with aspirin (120 mg/kg/day). Diabetes was induced by high-fat feeding and a low dose of streptozotocin (30 mg/kg). After treatment, plasma glucose, insulin, lipids, free fatty acids (FFAs) concentrations and serum TNF-alpha were determined. The expression of NF-kappaB in hepatocytes was analyzed by immunohistochemistry and western blot. The results showed administration of aspirin caused no significant lowering in fasting glucose level but significant reduction of hepatic NF-kappaB expression and serum TNF-alpha level with improved insulin resistance compared to the diabetic group. The relevant analysis showed positive correlation between the expression of homeostasis model assessment-insulin resistance (HOMA-IR) and NF-kappaB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-alpha (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-kappaB activation and TNF-alpha level in streptozotocin-induced type 2 diabetic rats.

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50 percent protein-calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20 percent alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (~10 g/100 g, P>.05) was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

Insulin sensitizing actions of fenugreek seed polyphenols, quercetin & metformin in a rat model.

Background & objectives: Plant polyphenols have been known to exert anti-diabetic action and promote insulin action. The present study was carried out to compare the effects of administration of fenugreek seed polyphenolic extract (FPEt), quercetin and metformin (a positive control) in an acquired model of insulin resistance (IR). Methods: Adult male Wistar rats divided into seven groups (n=12). IR was induced in groups (groups 2, 3, 4 and 5) by feeding a high fructose diet (FRU) (60 g/100 g diet) for 60 days. From day 16, FRU rats were administered either FPEt (200 mg/kg bw) (group 3), quercetin (50mg/kg bw) (group 4) or metformin (50 mg/kg bw) (group 5) for the next 45 days. Group 1 served as normal control while groups 6 and 7 served as FPEt and quercetin controls respectively. Oral glucose tolerance test (OGTT) was done on day 59 to assess glucose tolerance. At the end of 60 days, the levels of glucose, insulin, triglycerides (TG) and free fatty acids (FFA) were measured in the blood and the activities of insulin-inducible and suppressible enzymes in cytosolic and mitochondrial fractions of liver and skeletal muscle. The extent of tyrosine phosphorylation of proteins in response to insulin was determined by assaying protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) in liver. Results: Fructose caused increased levels of glucose, insulin, TG and FFA, alterations in insulin sensitivity indices, enzyme activities and reduced glycogen content. Higher PTP activity and lower PTK activity suggest reduced tyrosine phosphorylation status. Administration of FPEt or quercetin improved insulin sensitivity and tyrosine phosphorylation in fructose-fed animals and the effect was comparable with that of metformin. Interpretation & conclusions: Our findings indicated that FPEt and quercetin improved insulin signaling and sensitivity and thereby promoted the cellular actions of insulin in this model.

Seasonal variation and food deprivation in common vampire bats (Chiroptera: Phyllostomidae)

The aim of this study was to investigate the effects of seasonal variation and fasting on fat reserves of the common vampire bat Desmodus rotundus. Plasma free fatty acids (FFA), along with lipid content of the liver and muscles, and fatty acids from the carcass were obtained from bats fed bovine blood and from whom food was subsequently withheld for 24 and 48 h. Animals were caught during both dry and rainy seasons. In general, fat tissue stores were not significantly influenced by seasonal variation. Lipid content of liver, muscles, and carcass decreased during some food deprivation periods, although the concomitant increase expected in plasma FFA was not observed. Lipid metabolism is hypothesized as being continued by the tissues themselves. In addition, free access to food sources (e.g., domestic livestock) throughout the year is believed to contribute to the low seasonal variations in fat reserves observed in the common vampire bat.

Os efeitos da variação sazonal e do jejum sobre as reservas lipídicas do morcego vampiro comum (Desmodus rotundus) foram investigadas a fim de se estabelecer o padrão do metabolismo de lipídios da espécie e possíveis alterações sazonais. Foram determinadas as concentrações de Acidos Graxos Livres (AGL) e o conteúdo lipídico no fígado, músculos e na carcaça de animais alimentados (sangue bovino) e jejuados por 24 e 48 h, capturados durante as estações seca e chuvosa. Em geral, os depósitos lipídicos teciduais não apresentaram variações significativas em resposta às diferentes estações. As reservas de gordura diminuíram, no entanto, em resposta ao jejum, apesar de não ter sido observado nenhum aumento simultâneo dos AGL no plasma, aumento que normalmente indica mobilização lipídica. O metabolismo lipídico nestes tecidos parece importante para as necessidades energéticas dos próprios tecidos. Fatores como abundância e facilidade de acesso às presas (bovinos) podem estar contribuindo para a baixa variabilidade sazonal das reservas lipídicas teciduais.

Ketosis resistance in under thirty diabetic subjects.

Young onset diabetic subjects in tropical developing countries include a group of subjects who exhibits a characteristic ketosis resistance termed as Malnutrition Related Diabetes Mellitus (MRDM) by the WHO Study Group. The mechanism for this resistance to ketosis is still uncertain. To understand this mechanism we have studied the serum responses of glucose, non-esterified fatty acid (NEFA) and triglyceride (TG) to intravenous fat emulsion in newly diagnosed 8 fibrocalculous pancreatic diabetes (FCPD) and 11 low insulin secretory (LIS) subjects under 30 years of age along with 27 age-matched Non Insulin Dependent Diabetes Mellitus (NIDDM) subjects. Overnight fasting subjects were given a 90 min infusion of intralipos 10% (2.5 mg/kg body weight/min) and serum was collected at 0, 60, 90, 120 and 150 min. The fasting NEFA in the 3 groups were almost similar (micromol/l, M +/- SEM: 486 +/- 58, 564 +/- 76 and 559 +/- 34 in FCPD, LIS and NIDDM respectively). Fasting TG also showed a close similarity among 3 groups (mg/dl, M+/-SEM: 117 +/- 11, 110 +/- 22 and 123 +/- 4 in FCPD, LIS and NIDDM respectively). Intravenous fat caused a steady rise of NEFA as well as TG in all groups during the 90 minutes of infusion followed by a gradual fall. No two groups significantly differed regarding NEFA and TG at any time point. Fasting glucose was markedly higher in FCPD (22.9 +/- 2.5, mmol/l, M+/-SEM) and LIS (20.8 +/- 1.6) than NIDDM (11.0 +/- 1.0). In all the 3 groups glucose showed a slow but steady fall. Fasting C-peptide was very low in FCPD (0.42 +/- 0.08, ng/ml, M +/- SEM) and LIS (0.55 +/- 0.09) whereas it was within normal range in NIDDM patients (2.99 +/- 0.24). The results suggest the following: (a) Depleted body fat store do not lead to a decreased supply of NEFA in FCPD and LIS subjects at the fasting state; (b) Increased supply of NEFA in these subjects lead to a normal esterification response as evidenced by a parallel rise of TG; (c) Inspite of markedly low level of the antilipolytic hormone insulin, FCPD and LIS subjects are capable to maintain NEFA and TG responses similar to NIDDM subjects. This may indicate that factor (s) other than substrate and esterification is (are) probably involved in the ketosis resistance of FCPD and LIS subjects; and (d) Although FCPD and LIS differ regarding generalized pancreatic damage (which raises the possibility of involvement of glucagon producing alpha-cells in the FCPD group) the two groups do not differ regarding the ketogenic substrate and esterfication responses.

Plasma concentrations of non-esterified fatty acids in chronic renal failure in the United Arab Emirates

In end-stage renal failure, dyslipoproteinemia is linked to risk of cardiovascular disease. Increased concentrations of triacylglycerol-rich, very low density lipoproteins [VLDL] and decreased concentrations of high density lipoproteins [HDL] are usual, whilst total cholesterol and low density lipoprotein [LDL] concentrations are not increased. Non-esterified fatty acids [NEFA] are not transported by lipoproteins, but increased concentrations may also be associated with cardiovascular disease risk. In this study, plasma concentrations of NEFA and other lipids were compared in healthy subjects and patients with end-stage chronic renal failure who were either undialyzed or undergoing peritoneal dialysis or hemodialysis. Fasted blood samples for measurement of albumin, total, free and HDL-cholesterol, triacylglycerols and NEFA were taken from 56 apparently healthy subjects and from 48, 28 and 46 patients from the United Arab Emirates during 2002 who were either untreated or on peritoneal or hemodialysis. Hemodialysis subjects were studied immediately before and after a single treatment session. For all groups of patients, total, and LDL-cholesterol were unchanged, triacylglycerols and free cholesterol were raised and HDL-cholesterol concentrations and the percentage of esterified cholesterol were significantly decreased compared to controls. Plasma NEFA concentrations for untreated patients were similar to controls, but were decreased in peritoneal dialysis patients and markedly increased both before and, even more so, after dialysis in hemodialysis patients. Patients with end-stage renal failure share common features of dyslipoproteinemia irrespective of whether they are untreated or on peritoneal dialysis or hemodialysis. However, only hemodialysis patients show significantly increased concentrations of NEFA

Effect of Garcinia cambogia extract on lipids and lipoprotein composition in dexamethasone administered rats.

Dexamethasone (10 mg/kg body weight/day, s.c.) administered rats were treated with or without Garcinia cambogia fruit extract (1 g/kg body weight/day, orally) for 8 days. The administration of dexamethasone resulted in marked increase in the levels of triglycerides and cholesterol and free acids in both plasma and liver. The level of phospholipids increased in the plasma but decreased significantly in liver tissue after dexamethasone administration as compared to those in normal rats. The activities of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase were lowered significantly after dexamethasone per se administration. The levels of HDL-triglycerides and HDL-cholesterol remained unchanged, while the LDL and VLDL increased significantly in dexamethasone administered rats. The lipid levels were maintained at near normalcy when co-treated with Garcinia cambogia extract in dexamethasone administered rats. This study reveals the undesirable changes in lipid profile on dexamethasone administration and the hypolipidemic property of Garcinia cambogia extract.

Tryptophan and tyrosine catabolic pattern in neuropsychiatric disorders.

Catabolism of tryptophan and tyrosine in relation to the isoprenoid pathway was studied in neurological and psychiatric disorders. The concentration of trytophan, quinolinic acid, kynurenic acid, serotonin and 5-hydroxyindoleacetic acid was found to be higher in the plasma of patients with all these disorders; while that of tyrosine, dopamine, epinephrine and norepinephrine was lower. There was increase in free fatty acids and decrease in albumin (factors modulating tryptophan transport) in the plasma of these patients. Concentration of digoxin, a modulator of amino acid transport, and the activity of HMG CoA reductase, which synthesizes digoxin, were higher in these patients; while RBC membrane Na+-K+ ATPase activity showed a decrease. Concentration of plasma ubiquinone (part of which is synthesised from tyrosine) and magnesium was also lower in these patients. No morphine could be detected in the plasma of these patients except in MS. On the other hand, strychnine and nicotine were detectable. These results indicate hypercatabolism of tryptophan and hypocatabolism of tyrosine in these disorders, which could be a consequence of the modulating effect of hypothalamic digoxin on amino acid transport.

Efecto de la hormona somatotropica sobre la secrecion de insulina de perros cachorros / Effect of somatotropic hormone on insulin secretion in pups

En el presente estudio se abordó el efecto de la somatotropina de origen bovino (bSTH) en el perro cachorro. Se pbservó el perfil diario caracterizado por un incremento de la insulina inmunorreactiva sérica (IIR) a partir de las 6h de la administración subcutánea de bSTH, el cual se mantiene por 24h. La glicemia permaneció dentro de los límites normales observados en el periodo control, mientras que los ácidos grasos libres sufrieron un incremento significativo. La adminsitración intravenosa de glucosa, a las 24h de una segunda dosis de bSTH, prodyjo una excursión de la glucemia dentro de límites normales, con un exagerado aumento de la IIR, creando una situación que semeja los estados de resistencia insulínica. Los resultados señalan en el cachorro una respuesta cualitativamente similar a del perro adulto, en la cual la hiperinsulinemia debe jugar papel importante en el sostenimiento de la normoglicemia.

Natural estrous cycle in normal and diabetic bitches. II) serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum monesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similary shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches "in season" (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by "sex seasons"; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum FG base line was not changed by "sex seasons". During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisions in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin dificiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches "in season" studied here. The unability of these animals for hydrolizingglyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses...

Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats

In order to evaluate the role of visceral and subcutaneous fat tissue in insulin sensitivity and lipid metabolism, we measured the fasting levels of plasma free fatty acid (FFA) and insulin, glucose disappearance rate (Rd), and hepatic glucose production rate (HGP) after surgical removal of visceral (VF) or subcutaneous (SF) fat tissue in monosodium glutamate-obese (MSG-Ob) rats. Monosodium glutamate obesity was induced in rats by neonatal injection of MSG. Surgery to remove fat was done at 15 weeks of age. The experiments were done four weeks after the surgery. MSG-Ob rats showed increased levels of FFA, insulin, and HGP and decreased Rd compared to normal rats. In the VF group, the FFA level and HGP were decreased to normal values, Rd was partially normalized, but the level of insulin did not change significantly compared to MSG-Ob. In the SF group, FFA and Rd were partially normalized, but HGP was not suppressed significantly compared to MSG-Ob. These results suggest that visceral fat affects the insulin sensitivity of liver and FFA concentration more than subcutaneous fat; however, no significant difference was shown on whole body insulin sensitivity and fasting insulin concentration.

Effects of caffeine on time to exhaustion in exercise performed below and above the anaerobic threshold

Controversy still exists concerning the potential ergogenic benefit of caffeine (CAF) for exercise performance. The purpose of this study was to compare the effects of CAF ingestion on endurance performance during exercise on a bicycle ergometer at two different intensities, i.e., approximately 10 percent below and 10 percent above the anaerobic threshold (AT). Eight untrained males, non-regular consumers of CAF, participated in this study. AT, defined as the intensity (watts) corresponding to a lactate concentration of 4mM, was determined during an incremental exercise test from rest to exhaustion on an electrically braked cycle ergometer. On the basis of these measurements, the subjects were asked to cycle until exhaustion at two different intensities, i.e., approximately 10 percent below and 10 percent above AT. Each intensity was performed twice in a double-blind randomized order by ingesting either CAF (5 mg/kg) or a placebo (PLA) 60 min prior to the test. Venous blood was analyzed for free fatty acid, glucose, and lactate, before, during, and immediately after exercise. Rating of perceived exertion and time to exhaustion were also measured during each trial. There were no differences in free fatty acids or lactate levels between CAF and PLA during and immediately after exercise for either intensity. Immediately after exercise glucose increased in the CAF trial at both intensities. Rating of perceived exertion was singificantly lower (CAF = 14.1 + 2.5 vs PLA = 16.6 + 2.4) and time to exhaustion was significantly higher (CAF = 46.54 + 8.05 min vs PLA = 32.42 + 14.81 min) during exercise below AT with CAF. However, there was no effect of CAF treatment on rating of perceived exertion (CAF = 18.0 + 2.7 vs PLA = 17.6 + 2.3) and time to exhaustion (CAF = 18.45 + 7.28 min vs PLA = 19.17 + 4.37 min) during exercise above AT. We conclude that in untrained subjects caffeine can improve endurance performance during prolonged exercise performed below AT and that decrease of perceived exertion can be involved in this process.

Metabolic responses to repeated infusions of identical doses of norepinephrine in chronically energy deficient human subjects.

The physiological effects of three 30 min infusions of identical doses of norepinephrine (0.15 microgram/kg FFM/min) separated by 60 min intervals were assessed in well nourished (WN; n = 6) and chronically energy deficient (CED; n = 6) subjects. Each subject also underwent control, vehicle infusions with 0.9 per cent saline on a separate day. Oxygen consumption (VO2) was significantly higher during the third infusion of NE as compared to the first in both groups. This increment in VO2 occurred despite similar plasma peak NE levels in both infusions. Increments in plasma glucose and free fatty acids were also similar during the first and third infusions. The study demonstrates that thermogenic potentiation which we had earlier demonstrated in WN subjects, occurs in CED subjects as well. Thermogenic potentiation is not associated with altered plasma NE kinetics or mobilisation of substrates.