Hepatic and biochemical repercussions of a polyunsaturated fat-rich hypercaloric and hyperlipidic diet in Wistar rats / Repercussões hepáticas e bioquímicas da dieta hipercalórica e hiperlipídica rica em gordura poliinsaturada em ratos Wistar

CONTEXT: Non-alcoholic fatty liver disease is characterized by lipid deposits in the hepatocytes and has been associated with obesity, dyslipidemia and type-2 diabetes. It is considered a hepatic manifestation of the metabolic syndrome, of which the main component is insulin resistance leading to hyperinsulinemia and increased production of inflammatory cytokines. Saturated fat promotes hypertriglyceridemia and hyperinsulinemia, reduces levels of high-density cholesterol and increases levels of low-density cholesterol, while polyunsaturated fat is associated with hypolipidemic, antiinflammatory and imunoregulating action. OBJECTIVE: To evaluate the hepatic and biochemical repercussions of a polyunsaturated fat-rich diet in Wistar rats. METHODS: Twenty-two rats were distributed equally in two groups: GI - standard diet (Biobase Bio-tec Ratos e Camundongos®) providing 3.000 kcal/kg and GII - hypercaloric and hyperlipidic diet providing 4.250 kcal/kg (ω-6:ω-3 = 3:1). The animals were euthanized after 23 weeks of experiment. The weight, biochemical parameters and hepatohistological changes were registered. RESULTS: Findings were submitted to variance analysis with the level of statistical significance at 5 percent. The average weight did not differ significantly between the groups at baseline (P = 0.711), but was greater in Group II by the end of the experiment (P = 0.000). The levels of triglycerides (P = 0.039), total cholesterol (P = 0.015) and HDL (P = 0.005) were higher in Group I than in Group II. Macrovesicular steatosis was significantly more common in Group II than in Group I (P = 0.03). CONCLUSION: Hypercaloric and hyperlipidic diet rich in polyunsaturated fat promotes weight gain and favors the development of hepatic steatosis while reducing serum levels of triglycerides, total cholesterol and HDL.

CONTEXTO: A doença hepática gordurosa não-alcoólica caracteriza-se por depósito de lipídios nos hepatócitos. Desperta grande interesse por sua associação com obesidade, dislipidemias e diabetes mellitus tipo 2. É considerada a manifestação hepática da síndrome metabólica, cujo principal componente é a resistência à insulina, com consequente hiperinsulinemia e produção aumentada de citocinas inflamatórias. Dietas ricas em gorduras saturadas promovem hipertrigliceridemia, diminuição do colesterol de alta densidade, aumento do colesterol de baixa densidade e hiperinsulinemia, enquanto dietas ricas em gordura poliinsaturada podem apresentar efeitos hipolipidêmicos, antiinflamatórios e imunorreguladores. OBJETIVO: Investigar as repercussões hepáticas e bioquímicas da dieta rica em gordura poliinsaturada em ratos Wistar. MÉTODOS: Os animais (22) foram distribuidos nos grupos GI-dieta padrao (Biobase Bio-tec Ratos e Camundongos®) com 3000 kcal/kg e GII-dieta hipercalorica e hiperlipidica, com 4250 kcal/kg, relação ω-6: ω-3 = 3:1. Foram mortos apos 23 semanas de administração das dietas. Avaliaram-se peso, exames bioquimicos e alteracoes histológicas do fígado. RESULTADOS: Foram utilizados testes de análise de variância com nível de significância de 5 por cento (P<0,05). Não houve diferença significante na média de peso entre os grupos (P = 0,711) no início, entretanto GII apresentou maior média que GI ao final do experimento (P = 0,000). GI mostrou níveis significantemente mais elevados de triglicerídeos (P = 0,03), colesterol total (P = 0,039) e HDL (P = 0,015) do que GII. O GII apresentou maior média de esteatose macrovesicular do que GI (P = 0,005). CONCLUSÃO: A dieta hipercalórica e hiperlipídica, rica em gordura poliinsaturada, promove esteatose hepática e incremento de peso, contudo reduz os níveis séricos de triglicerídeos, colesterol total e HDL.

Trabajos de Investigación Increase of plasma fatty acids without changes in n-6/n-3-PUFA ratio in asymptomatic obese subjects / Aumento de las concentraciones plasmáticas de ácidos grasos sin cambio en el ratio de n-6/n-3 PUFA en sujetos obesos asintomáticos

Obesity is associated with a low grade inflammation which contributes to the development of insulin resistance and diabetes. The aim of this study was to assess the total saturated (SFAs), monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) in plasma from asymptomatic obese subjects and to determine the arachidonic/eicosapentanoic acid ratio [ARA/EPA] as a marker of inflammation, and its eventual association with ultrasensitive CRP. Fourteen obese (34.4 ± 11.1y.; BMI: 36.0 ± 4,5 kg/m2) and 12 normal-weight (30.6 ± 7.8y.; BMI: 23,6± 2,4 kg/m2) subjects were recruited and their plasma fatty acids were determined by gas chromatography. usCRP was higher in the obese subjects (p=0,01) and correlates with their body fat content. The percentages of SFAs, MUFAs, PUFAs were not affected in the obese subjects but their concentrations were increased, compared with the control group. However, no differences in the long chain PUFAs (DHA and EPA) concentrations or in the plasmatic ARA/EPA ratio were observed in these subjects. These observations do not support a relation between the ARA/EPA ratio and the presence of low grade inflammation evaluated by plasma usCRP in this group of asymptomatic obese subjects.

La obesidad está asociada con una inflamación de bajo grado que contribuye al desarrollo de la insulino-resistencia y de la diabetes. El objetivo de este estudio fue evaluar las concentraciones plasmáticas de ácidos grasos saturados (AGS), monoinsaturados (AGMI) y poliinsaturados (AGPI) en sujetos obesos asintomáticos y determinar el ratio ácido araquidónico/ácido eicosapentanoico [ARA/EPA] como un posible marcador de inflamación, con su eventual asociación con los niveles de proteína C reactiva ultrasensible (PCRus). Se reclutaron 14 sujetos obesos (34,4 ± 11.1 años; índice de masa corporal: 36,0 ± 4,5 kg/m2) y 12 normopeso (30,6 ± 7.8 años; índice de masa corporal: 23,6 ± 2,4 kg/m2); las concentraciones plasmáticas de ácidos grasos fueron determinados por cromatografía de gases. Los niveles de PCRus fueron más elevadas en los sujetos obesos (p=0,01) y correlacionaron con el contenido de grasa corporal. Los porcentajes relativos de AGS, AGMI, AGPI no se vieron afectados en los sujetos obesos, pero sus concentraciones plasmáticas se incrementaron en comparación con el grupo control. Sin embargo, no se observaron diferencias en las concentraciones de PUFAs de cadena larga (DHA, EPA y ARA) ni en el ratio ARA/EPA en los sujetos obesos. Estas observaciones no apoyan el uso del ratio ARA/EPA como un marcador de inflamación de bajo grado evaluada por PCRus en este grupo de sujetos obesos asintomáticos.

[Plasma fatty acids Profile and lipids in Tunisian male elite athletes]

Growing interest is accorded to polyunsaturated fatty acids [PUFAs] 3, which are considered beneficial for health. To investigate the effect of sports on plasma lipids and fatty acids [FAs], especially 6 and 3 PUFAs and the 6/3 ratio. The study included 75 Tunisian male elite athletes, practicing team sport and 70 sedentary healthy men as controls. Plasma FAs profile was analyzed by gas chromatography. Comparison between groups was performed using a univariate GLM analysis, with adjustment on age, body mass and energy intake. Athletes showed lower triglycerides and saturated FAs [27.64% +/- 2.17% vs. 30.41% +/- 4.35%] and increased HDL cholesterol and monounsaturated FAs [21.19% +/- 2 44% vs. 19.12% +/- 3.03%]. However, there was no significant difference in total PUFAs, 6 and 3 families and 6/3 ratio [10.15% +/- 3.24% vs. 10.20% +/- 3.37%] between athletes and sedentary. Sport favorably modifies the profile of plasma FAs by increasing monounsaturated FAs at the expense of saturated FAs, but has no effect on total PUFAs, and 6 and 3 families. A diet rich in 3 PUFAs would lower the 6/3 ratio, in order to improve the health and probably the performance of athletes

Assessment of the role of polyunsaturated fatty acids in chronic kidney disease

Recent evidence suggests a relationship between abnormalities of polyunsaturated fatty acids [PUFAs] and the development of chronic kidney disease [CKD].To assess plasma concentration levels of n-6 PUFAs in CKD patients to clarify their role in the development and progression of the kidney disease in an attempt to provide an early protective therapeutic strategy. Fifty eight CKD patients as well as thirty healthy controls were enrolled and subjected to thorough clinical assessment and laboratory investigations including kidney function tests [serum urea, creatinine, total proteins and albumin], lipid profile [total cholesterol, triglycerides, high density lipoprotein-cholesterol [HDL-C], low density lipoprotein-cholesterol [LDL-C] and atherosclerotic risk ratio [T-Cholesterol/HDL-C]] in addition to analysis of PUFAs of the n-6 series which include linoleic, gamma-linolenic and arachidonic acids by high performance liquid chromatography [HPLC]. A highly significant decrease of gamma-linolenic and arachidonic acids was detected in CKD patients as compared to controls, while linoleic acid was elevated in CKD patients, however this elevation was statistically insignificant when compared to the control group. The correlation study showed that each of gamma-linolenic acid and arachidonic acid were significantly positively correlated with creatinine clearance and HDL-C and significantly negatively correlated with triglycerides, LDL-C and risk ratio. Meanwhile, linoleic acid showed a significant positive correlation with triglycerides and insignificant correlations with creatinine clearance, total cholesterol, HDL-C, LDL-C and risk ratio. The long chain n-6 fatty acids gamma-linolenic and arachidonic acids are present in insufficient amounts in plasma of CKD patients and such insufficiency increases with the severity of the kidney disease confirming the role of impaired n-6 PUFAs metabolism in the development and progression of CKD. Thus, high dietary intake of n-6 fatty acids [mainly gamma-linolenic acid] could be recommended as a new therapeutic strategy in CKD patients aiming at interrupting the irreversible process of renal fibrosis and ameliorating chronic renal injury and may also be protective against the development of cardiovascular disease among those patients

Erythrocyte membrane, plasma and atherosclerotic plaque lipid pattern in coronary heart disease / Perfil lipídico de membrana de eritrocito, plasma y placa ateromatosa en la enfermedad coronaria

The objective was to analyze the lipid composition of the atherosclerotic plaque (AP), plasma and erythrocyte membrane (EM) in patients with advanced coronary heart disease (CHD). AP were obtained through endarterectomy in 18 patients. Ten normolipemic healthy subjects were selected to obtain the normal lipid pattern profile. Total lipids of AP and EM were determined by HPTLC, and the fatty acid profile from AP, EM and plasma using TLC-FID. The relative amount of the lipid species analyzed in AP was in line with the data in the literature [phospholipids: 23.5 mol% more or less 3.5; total cholesterol 68.9 mol% more or less 7.9; triglyceride 7.6 mol% more or less 3.4]. Plasma and EM from CHD patients compared to controls, showed a decrease in polyunsaturated fatty acids and an increase in saturated fatty acids leading to a decrease in the unsaturation index (plasma: 1.67 more or less 0.06 vs. 1.28 more or less 0.03, P less than 0.05; EM: 2.28 more or less 0.04 vs. 1.25 more or less 0.010, P less than 0.05) and an enhancement in the saturated/unsaturated ratio (plasma: 0.35 more or less 0.02 vs. 0.52 more or less 0.02, P less than 0.05; EM: 0.45 more or less 0.01 vs. 0.83 more or less 0.04, P less than 0.05). These data are consistent with an essential fatty acid deficiency. Total cholesterol was increased in the CHD's EM (32.3 more or less 0.8 vs. 40.6 more or less 2.5, P less than 0.05) with a decrease in phospholipid percentage (67.7 more or less 0.7 vs. 59.4 more or less 2.6, P less than 0.05) indicating an alteration in membrane fluidity. These findings suggest changes in EM lipids in CHD patients in spite of different pathological conditions such as age, smoking status and diabetes. The analysis of the lipid composition of EM could provide a useful tool to monitor the evolution of the CHD.

El objetivo fue analizar la composición lipídica de las membranas de eritrocitos (ME), plasma y placas ateromatosas (PA) en pacientes con enfermedad coronaria avanzada (ECV). Las PA fueron obtenidas de endarterectomías coronarias de 18 pacientes. Fueron seleccionados 10 sujetos sanos, normolipémicos, como grupo control. Los lípidos totales de PA y ME se determinaron utilizando HPTLC, y el perfil de ácidos grasos de las PA, ME y plasma mediante TLC-FID. La cantidad relativa de las especies lipídicas obtenidas de las PA coinciden con la literatura [fosfolípidos 23.5 mol% más o menos 3.5; colesterol total 68.9 mol% más o menos 7.9; triglicéridos 7.6 mol% más o menos 3.4]. En el plasma y en las ME de los pacientes con ECV se observó, comparando con los pacientes controles, una disminución de los ácidos grasos poli-no saturados acompañado de un aumento de los ácidos grasos saturados que provocó el descenso del índice de instauración (plasma: 1.67 más o menos 0.06 vs. 1.28 más o menos 0.03, P menor que 0.05; ME: 2.28 más o menos 0.04 vs. 1.25 más o menos 0.010, P menor que 0.05) y el incremento del cociente AG saturados/insaturados (plasma: 0.35 más o menso 0.02 vs. 0.52 más o menos 0.02, P menor que 0.05; ME: 0.45 más o menos 0.01 vs. 0.83 más o menos 0.04, P menor que 0.05). Estos datos indicarían una deficiencia de ácidos grasos esenciales. Se observó una elevación en los valores de colesterol total (32.3 más o menos 0.8 vs. 40.6 más o menos 2.5, P menor que 0.05) y una disminución de los valores de fosfolípidos (67.7 más o menos 0.7 vs. 59.4 más o menos 2.6, P menor que 0.05) en las ME de los pacientes con ECV. Estos hallazgos sugieren cambios en los lípidos de las ME en los pacientes con ECV a pesar de presentar diferencias con respecto a edad, tabaquismo y diabetes. El conocimiento del perfil lipídico de las ME podría constituirse en una herramienta útil para monitorear la evolución de la enfermedad.

Effect of pregnancy on plasma lipid concentration in Trinidadian women. Result of a pilot study

In Trinidad and Tobago, cardiovascular disease and Type 2 diabetes mellitus are important causes of morbidity and mortality, and birth weight is significantly less than reference standards. Lower birth weight is associated with increased risk of these diseases. Variation in birth weight is due, in part, to deposition of adipose tissue in the foetus during the last trimester at the same time that maternal plasma triacylglycerol (TAG) increases. We conducted a pilot cross-sectional analysis of maternal plasma lipid status and birth weight in healthy, non-pregnant, primigravida Trinidadian women. Non-pregnant and pregnant women, in their second and third trimesters, and at term, were recruited at random from an antenatal clinic. Adult and umbilical cord plasma TAG, non-esterified fatty acids (NEFA) and phosphatidylcholine (PC) concentrations were determined from gas chromatographic analysis of fatty acids. Maternal height, weight, skinfold thickness and infant birth weight were measured. The infants born to Afro-Trinidadian and Indo-Trinidadian women were of low to normal birth weight (medians 3.07 and 3.22 kg, respectively). At term, plasma TAG concentration was approximately two fold (p < 0.05) greater than for non-pregnant women. The increment between 30-34 weeks was 1.5 to 1.9 fold lower than reported in other populations. There was a strong relationship (r = 0.8771, p = 0.019) between maternal and cord plasma TAG and NEFA, but not PC concentrations. There was no significant relationship between maternal TAG concentration at term and birth weight. The result suggests an impaired ability to increase plasma TAG concentrations during late gestation.

Lipid abnormalities in chronic renal failures undergoing hemodialysis

Lipid abnormalities are common in patients with renal disease, probably contributing to the high incidence of cardiovascular diseases in this population. In this study we determined the plasma and erythrocyte lipid profile in patients with chronic renal failure (CRF) along 30 months under hemodialysis. In the same patients the influence of cuprophane and polysulphone dialysis membranes on the fatty acid pattern of plasma and erythrocytes, before and after dialysis, was also studied. Fluidity in erythrocyte membranes was also assessed by diphenylhexatriene (DPH) fluorescence polarization measurements. Triglyceride levels were increased in the plasma and in erythrocyte membranes of CRF patients compared to healthy subjects. Plasma polyunsaturared fatty acids decreased whereas palmitic and monounsaturated acids increased in CRF patients. No changes were observed in either the fatty acid profile or DPH fluorescence anisotropy of erythrocyte membranes. The lipid composition abnormalities persisted after 18 months and they became more notorious after 30 months. Neither the plasma nor the erythrocyte membrane lipid pattern changed in CRF patients during the dialysis session, regardless of the dialysis membrane used. We conclude that CRF patients under regular hemodialysis evidence a gradual deteriorarion in the fatty acid and triglyceride abnormalities, a finding that might be relevant to the risk of cardiovascular disease in this setting.

Acidos grasos poliinsaturados de cadena larga en eritrocitos de prematuros alimentados por vía enteral con leche humana de pretérmino o con una fórmula convencional / Long chain polyunsaturated fatty acids in erythrocytes of preterm babies enterally feed with maternal milk or with a convencional formula

Objetivo: estudiar el efecto de alimentar prematuros sanos con peso adecuado para la edad gestacional (RNPrT-AEG) con una fórmula convencional (FC) que no aporta ácidos grasos poliinsaturados de cadena larga o con leche humana de pretérmino (CMPrT), sobre el contenido de ácidos grasos de cadena larga en los fosfolípidos de sus eritrocitos al tercer día de vida. Método: se comparó la composición porcentual de los ácidos grasos saturados, monoinsaturados y poliinsaturados, de la fracción fosfolípidica de eritrocitos, en RNPrT-AEG en sangre de cordón y al tercer día de vida, después de ser alimentados por vía enteral con FC o CMPrT. Así mismo se compararon los resultados con los obtenidos en recién nacidos de término (RNT) alimentados con leche humana de término (CMT). Resultados: tanto los RNPrT-AEG alimentados con FC como con CMPrT disminuyeron los niveles de ácidos grasos monoinsaturados al tercer día de vida (17,8 y 17,5 vs 19,2 por ciento, respectivamente, p < 0,05). Los RNPrT-AEG alimentados con CMPrT mantuvieron el contenido de ARA y DHA (12,6 y 4 vs 12,1 y 3,6 por ciento respectivamente), en tanto que los alimentados con FC disminuyeron significativamente el ácido araquidónico y docosahexaenoico (11,5 y 3 vs 12,1 y 3,6 por ciento respectivamente, p < 0,05), y todos los ácidos grasos poliinsaturados de cadena larga (mayor igual 20 C; PCL), en sus eritrocitos. Al comparar al tercer día de vida los RNPrT vs RNT alimentados con calostro materno, los eritrocitos de los pretérmino tienen significativamente menos contenido de ARA y DHA (12,6 vs 13; 4 por ciento y 4 vs 4,7 por ciento, respectivamente, p < 0,05). Conclusión: el calostro materno de pretérmino permite mantener mejor el contenido de PCL a los 3 días de vida que la alimentación con una fórmula convencional, sin llegar a los niveles de PCL contenidos en eritrocitos de RNT alimentados con CMT. Los requerimientos nutricionales de los PCL de RNPrT-AEG, que deban alimentarse por vía enteral o parenteral, o que no puedan alimentarse con calostro materno, podrían cubrirse proporcionándoles precozmente fórmulas cuya cantidad y composición lipídica se asemeje a la del calostro de madres con parto prematuro

Diferencia en la composición porcentual de los poliinsaturados de cadena larga en eritrocitos materno-fetales en nacimientos de término o pretérmino en humanos / Differences in the percentual composition of the long chain polyunsatureted in maternal and fetal erythrocytes in term and preterm birth in human

Se investiga el contenido y la distribución de los ácidos grasos altamente poliinsaturados de cadena larga (APCL) en los fosfolípidos de eritrocitos materno-fetales en sagre materna venosa y de cordón umbilical obtenida al momento de partos de término o pretérmino en humanos. Se selecionaron madres del mismo nivel socioeconómico, sanas. Once madres dieron a luz niños sanos de término (40 semanas), y veintidós niños sanos de pretérmino (32-34 semanas). Se obtuvo sangre venosa materna y sangre umbilical al momento del parto. Se aislaron los fosfolípidos de los eritrocitos, los ácidos grasos de los fosfolípidos se analizaron por cromatografía gas-líquida. Los resultados informan que en los fetos de término el contenido de todos los APCL omega 6 y omega 3 particularmente 20:4w6 (ARA), y 22:6w3 (DHA), se encontraron signigicativamente más altos que en su madre, a la inversa todos los APCL fueron significativamente menores en el feto pretérmino en relación a su madre. Al comparar contenidos de ARA y DHA entre los fetos se observó que sólo el DHA se encontró significativamente disminuido en fetos pretérmino. Las mujeres que dieron a luz niños de pretérmino demostraron una alta relación ARA/DHA en su sangre en relación a las mujeres con parto de término. De este estudio y tomando en cuenta la literatura preexistente se puede sugerir que un alto contenido de ARA en eritrocitos materno y fetales podría ser una señal de riesgo de prematuridad.

Effect of two cardiac glycosides, digitoxin and digoxin on blood lipids.

Two cardiac glycosides, namely digitoxin and digoxin when treated with goat blood, were found to alter the lipid constitution as measured by their phosphorus content, fatty acid composition and malonaldehyde content. There was significant increase in the poly-unsaturated fatty acids (PUFA) and malonaldehyde contents in blood treated with these drugs. Possible correlation between the lipophilicity of the drugs and their biological activity is discussed.

Effects of dietary lipidic charge in the concentration of bovine plasmatic lipids and lipoproteins. Its influence on the saturation degree of fatty acids' storaged lipids

Suplementando durante 7 meses la ración de bovinos media sangrecebú con semilla de algodón (19%) de grasa), a 30 animales se les incrementó la carga lipídica dietaria en un 2.6% (lote S), actuando 30, animales como controles (lote C). Otros 2 bovinos fueron sobredosificados con 7.9% de grasa adicionada (lote H). Mensualmente se les controló peso, estado clínico y niveles séricos de colesterol total (CT), triglicéridos (TG), lipoporteínas (LP) y otros parámetros bioquímicos. Al culminar el ensayo los novillos fueron sacrificados, efectuándose pruebas valorativas de calidad de carne y grasa. Los niveles iniciales de CT, estadísticamente homogéneos en los 3 grupos (X = 1.50 gm/l), permanecieron estables en C (1.53 gm/l), pero aumentaron progresivamente en los animales suplementados; al finalizar el ensayo fueron mayores en H (3(3.95 gm/l que en S (2.44 gm/l). Los TG (X inicial = 0.30 gm/l) también resultaron al final más elevados en H (0.74 gm/l) que en S (0.71 gm/l). El lipoproteinograma permaneció inalterados en C, registrándose incrementos de alfa LP y disminuciones de beta LP en los animales cuya carga lipídica había sido aumentada. Los incrementos del peso promedio por animal y por día fueron de 130 gm (C), 290 gm (S) y 88 gm (H); en los bovinos de este último lote se desmejoró su estado general. Comparando los lotes C y S, surge que el "block" de bifes de estos últimos fue más pesado (2.45 vs. 2.33 Kg), con mayor cantidad de lípidos (0.47 vs. 0.36 Kg) y mayor proporción de veteado graso (1.40 vs. 1.25%). Los lípidos de depósito presentaron mayor grado de saturación en S, incrementándose en promedio el porcentaje de ácido esteárico en un 28.6%. Los lípidos intramusculares también aumentaron su grado de satuación, resultando el porcentaje de ácido esteárico mayor en S (19.5%) que en C (16.3%)