RESUMEN
We have reported strong intrapair resemblances (IPRs) in serum phosphatidylcholine (PC) fatty acid composition within adult monozygotic twins living apart. This study assessed the contribution of genetic factors to changes in serum and adipose tissue fatty acids resulting from weight loss and followed by a subsequent year of weight maintenance. Eleven pairs of female obese monozygotic twins (age: 38.9 +/- 1.8; BMI: 32.5 +/- 0.9) were recruited for the study. Fasting serum and adipose tissue were obtained after 1 week of inpatient stabilization, after 1 month of inpatient very-low-calorie diet (VLCD), and again after 1 year of outpatient weight maintenance. Fatty acids in serum lipid fractions and adipose tissue were quantitated by gas chromatography. Using multiple regression adjusted for age and initial value, IPRs were determined for the changes induced by VLCD and by the year of weight maintenance. There were few IPRs in nonessential fatty acids. By contrast, there were numerous IPRs for essential fatty acids (EFA), especially in the n-3 family across the VLCD. Following the maintenance year, however, frequent IPRs for nonessential fatty acids were seen, particularly in serum PC, and strong IPRs were seen for 18:3 n-3 and 20:5 n-3 across multiple fractions. These results infer the existence of strong genetic factors determining both the nonessential and EFA compositions of tissue lipids in humans independent of diet. Of particular note were the consistent IPRs for n-3 fatty acids despite dietary stress, indicating that the conservation and distribution of this EFA family are subject to considerable genetic variance in humans.
Asunto(s)
Tejido Adiposo/metabolismo , Ácidos Grasos/metabolismo , Obesidad/metabolismo , Gemelos Monocigóticos , Pérdida de Peso , Adulto , Cromatografía de Gases , Ácidos Grasos/sangre , Femenino , Humanos , Obesidad/sangre , Obesidad/terapiaRESUMEN
OBJECTIVE: The metabolism of arachidonic acid (AA) has been shown to be altered in severe insulin resistance that is present in obese (fa/fa) Zucker rats. We examined the effects and mechanism of action of AA on basal and glucose-stimulated insulin secretion in pancreatic islets isolated from obese (fa/fa) Zucker rats and their homozygous lean (Fa/Fa) littermates. RESEARCH METHODS AND PROCEDURES: Islets were isolated from 10- to 12-week-old rats and incubated for 45 minutes in glucose concentrations ranging from 3.3 to 16.7 mM with or without inhibitors of the cyclooxygenase or lipoxygenase pathways. Medium insulin concentrations were measured by radioimmunoassay, and islet production of the 12-lipoxygenase metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), was measured by enzyme immunoassay. RESULTS: In islets from lean animals, AA stimulated insulin secretion at submaximally stimulatory glucose levels (<11.1 mM) but not at 16.7 mM glucose. In contrast, in islets derived from obese rats, AA potentiated insulin secretion at all glucose concentrations. AA-induced insulin secretion was augmented in islets from obese compared with lean rats at high concentrations of AA in the presence of 3.3 mM glucose. Furthermore, the inhibitor of 12-lipoxygenase, esculetin (0.5 microM), inhibited AA-stimulated insulin secretion in islets from obese but not lean rats. Finally, the islet production of the 12-HETE was markedly enhanced in islets from obese rats, both in response to 16.7 mM glucose and to AA. DISCUSSION: The insulin secretory response to AA is augmented in islets from obese Zucker rats by a mechanism related to enhanced activity of the 12-lipoxygenase pathway. Therefore, augmented action of AA may be a mechanism underlying the adaptation of insulin secretion to the increased demand caused by insulin resistance in these animals.
Asunto(s)
Ácido Araquidónico/metabolismo , Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Lipooxigenasa/metabolismo , Obesidad/fisiopatología , Animales , Ácido Araquidónico/farmacología , Células Cultivadas , Glucosa/metabolismo , Insulina/farmacología , Secreción de Insulina , Masculino , Ratas , Ratas ZuckerRESUMEN
PURPOSE: There have been few randomized controlled trials of commercial weight-loss programs. This ongoing study compares the effects of a self-help program and a commercial program on weight loss and other measures of obesity in overweight and obese men and women. SUBJECTS AND METHODS: We report the results of the first 26 weeks of a multicenter, randomized, 2-year study of 423 subjects who had a body mass index of 27 to 40 kg/m(2). Subjects were randomly assigned to either a self-help program, consisting of two 20-minute sessions with a nutritionist and provision of printed materials and other self-help resources, or to attendance at meetings of a commercial program (Weight Watchers). Outcome measures were changes in body weight, body mass index, waist circumference, and body fat. Changes in serum homocysteine levels were measured in a subsample of participants during the first 12 weeks. RESULTS: After 26 weeks, subjects in the commercial program, as compared with those in the self-help program, had greater decreases in body weight [mean (+/- SD) -4.8+/-5.6 vs -1.4+/-4.7 kg] and body mass index (-1.7+/-1.9 vs -0.5+/-1.6 kg/m(2), both P<0.001) in intention-to-treat analyses. Among subjects measured at week 26, mean waist circumference (-4.3+/-10.5 vs -0.7+/-12.7 cm) and fat mass (-3.8 +/-7.0 vs -1.5+/-7.6 kg, both P<0.05) also decreased more among subjects in the commercial program. Mean serum homocysteine levels improved in the commercial program compared with self-help (-0.5+/-1.3 vs 0.9+/-1.8 microM, P<0.05). CONCLUSIONS: A structured commercial weight-loss program is more likely to be effective for managing moderately overweight patients than brief counseling and self-help.
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Promoción de la Salud , Ciencias de la Nutrición/educación , Obesidad/terapia , Autocuidado , Pérdida de Peso , Adulto , Anciano , Índice de Masa Corporal , Intervalos de Confianza , Dieta Reductora , Ejercicio Físico , Femenino , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/dietoterapia , Participación del Paciente , Evaluación de Programas y Proyectos de Salud , Sensibilidad y EspecificidadRESUMEN
Compared with the lean (Fa/-) genotype, obese (fa/fa) Zucker rats have a relative deficiency of muscle phospholipid arachidonate, and skeletal muscle arachidonate in humans is positively correlated with insulin sensitivity. To assess the hypothesis that the positive effects of exercise training on insulin sensitivity are mediated by increased muscle arachidonate, we randomized 20 lean and 20 obese weanling male Zucker rats to sedentary or treadmill exercise groups. After 9 wk, fasting serum, three skeletal muscles (white gastrocnemius, soleus, and extensor digitorum longus), and heart were obtained. Fasting insulin was halved by exercise training in the obese rat. In white gastrocnemius and extensor digitorum longus (fast-twitch muscles), but not in soleus (a slow-twitch muscle) or heart, phospholipid arachidonate was lower in obese than in lean rats (P < 0.001). In all muscles, exercise in the obese rats reduced arachidonate (P < 0.03, by ANOVA contrast). We conclude that improved insulin sensitivity with exercise in the obese genotype is not mediated by increased muscle arachidonate and that reduced muscle arachidonate in obese Zucker rats is unique to fast-twitch muscles.
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Ácido Araquidónico/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Obesidad/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Glucemia/metabolismo , Peso Corporal/fisiología , Ingestión de Alimentos/fisiología , Ácidos Grasos/metabolismo , Genotipo , Insulina/sangre , Masculino , Obesidad/genética , Fosfolípidos/metabolismo , Ratas , Ratas ZuckerRESUMEN
Circulating leptin decreases during fasting in rodents and humans; however, the mechanism of the decrease is unknown. The aim of this study was to examine the relationship between decrements of serum leptin concentrations and changes of hormonal (insulin and cortisol) and metabolic (glucose, ketones, and fatty acids) parameters involved in the metabolic adaptation to energy restriction in normal-weight humans. Because there are marked gender differences in circulating leptin, both men and women were studied. The body mass index (BMI), percent body fat (% body fat), and serum leptin, insulin, cortisol, glucose, beta-hydroxybutyrate,(BOHB), and nonesterified fatty acids (NEFA) were determined in 11 men and 13 women (age, 20 to 41 years; BMI, 21.2 to 26.8 kg/m2) before and during 7 days of energy restriction (-68% +/- 1% of daily energy requirements). Weight loss averaged about 4% in both men and women. Leptin in men was 3.7 +/- 0.5 and decreased to 2.1 +/- 0.4 ng/mL (percent change [%delta], -36% +/- 6.0%, P < .0005) during restriction. Concurrently, insulin decreased from 7.2 +/- 0.6 to 1.8 +/- 0.3 microU/mL (%delta, -74% +/- 4%, P < .0001). In contrast, leptin was higher in women before (16.2 +/- 1.9 ng/mL) and after (6.0 +/- 0.8 ng/mL) restriction and decreased more than in men (%delta, -61% +/- 4%, P < .02 v men), whereas the decrease of insulin in women was less than in men: 10.1 +/- 1.9 to 6.1 +/- 1.0 microU/mL (%delta, -31% +/- 9%, P < .0025; P < .0005 v men), perhaps because glucose decreased less in women than in men. Overall, the changes of leptin during fasting were independently correlated with the changes of glucose (r = .53, P < .007), NEFA (r = .53, P < .01), and BOHB (r = .65, P < .001). In addition, the change of leptin correlated with a combined index of the parameters that reflect decreased glucose availability and increased lipolysis ([deltaglucose + deltainsulin + deltaNEFA]/3, r = .73, P < .0001) or a combined index of parameters that would be expected to limit glucose uptake by adipocytes ([deltaglucose + deltainsulin + deltacortisol]/3, r = .48, P < .02). We conclude that there are significant differences between men and women in the responses of leptin and insulin to energy restriction. Furthermore, decreases of circulating leptin during negative energy balance are related to changes of endocrine and metabolic parameters, suggesting that leptin secretion may be regulated by alterations of adipocyte glucose and lipid metabolism, ie, decreased glucose uptake and metabolism and increased lipolysis.
Asunto(s)
Metabolismo Energético/fisiología , Hidrocortisona/sangre , Insulina/sangre , Obesidad/sangre , Proteínas/metabolismo , Adulto , Antropometría , Glucemia/metabolismo , Ingestión de Energía , Ácidos Grasos/sangre , Femenino , Humanos , Cetonas/sangre , Leptina , Modelos Lineales , MasculinoRESUMEN
While there are many reports of studies that fed arachidonic acid (AA) to animals, there are very few reports of AA feeding to humans under controlled conditions. This 130-d study was conceived as a controlled, symmetrical crossover design with healthy, adult male volunteers. They lived in the metabolic research unit (MRU) of the Western Human Nutrition Research (WHNRC) for the entire study. All food was prepared by the WHNRC kitchen. The basal (low-AA) diet consisted of natural foods (30 en% fat, 15 en% protein, and 55 en% carbohydrate), containing 210 mg/d of AA, and met the recommended daily allowance for all nutrients. The high-AA (intervention) diet was similar except that 1.5 g/d of AA in the form of a triglyceride containing 50% AA replaced an equal amount of high-oleic safflower oil in the basal diet. The subjects (ages 20 to 39) were within -10 to +20% of ideal body weight, nonsmoking, and not allowed alcohol in the MRU. Their exercise level was constant, and their body weights were maintained within 2% of entry level. Subjects were initially fed the low-AA diet for 15 d. On day 16, half of the subjects (group A) wee placed on the high-AA diet, and the other group (B) remained on the low-AA diets. On day 65, the two groups switched diets. On day 115, group B returned to the low-AA diet. This design, assuming no carryover effect, allowed us to merge the data from the two groups, with the data comparison days being 65 (low-AA) and 115 (high-AA) for group B and 130 (low-AA) and 65 (high-AA) for group A. The main indices studied were the fatty acid composition of the plasma, red blood cells, platelets, and adipose tissue; in vitro platelet aggregation, bleeding times, clotting factors; immune response as measured by delayed hypersensitivity skin tests, cellular proliferation of peripheral blood mononuclear cells in response to various mitogens and antigens, natural killer cell activity, and response to measles/mumps/rubella and influenza vaccines; the metabolic conversion of deuterated linoleic acid to AA and the metabolic fate of deuterated AA in the subjects on and off the high-AA diet; and the production of eicosanoids as measured by excretion of 11-DTXB2 and PGI2-M in urine. The results of these studies will be presented in the next five papers from this symposium.
Asunto(s)
Ácido Araquidónico/administración & dosificación , Grasas de la Dieta/farmacología , Alimentos Fortificados , Triglicéridos/farmacología , Adulto , Formación de Anticuerpos , Ácido Araquidónico/farmacología , Estudios Cruzados , Epoprostenol/orina , Ácidos Grasos/química , Humanos , Lípidos/sangre , Masculino , Agregación Plaquetaria/efectos de los fármacos , Tromboxanos/orina , Triglicéridos/metabolismoRESUMEN
Normal healthy male volunteers (n = 10) were fed diets (high-AA) containing 1.7 g/d of arachidonic acid (AA) for 50 d. The control (low-AA) diet contained 210 mg/d of AA. Dietary AA had no statistically significant effect on the blood cholesterol levels, lipoprotein distribution, or apoprotein levels. Adipose tissue fatty acid composition was not influenced by AA feeding. The plasma total fatty acid composition was markedly enriched in AA after 50 d (P < 0.005). The fatty acid composition of plasma lipid fractions, cholesterol esters, triglycerides, free fatty acids, and phospholipid (PL) showed marked differences in the degree of enrichment in AA. The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3% AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0% AA. The level of 22:4n-6 also was different (0.67 to 1.06%) in the plasma PL fraction after 50 d of AA feeding. After consuming the high-AA diet, the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid. These results indicate that dietary AA is incorporated into tissue lipids, but selectively into different tissues and lipid classes. Perhaps more importantly, the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding.
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Apolipoproteínas/sangre , Ácido Araquidónico/farmacología , Grasas de la Dieta/farmacología , Ácidos Grasos/química , Alimentos Fortificados , Lípidos/sangre , Lipoproteínas/sangre , Tejido Adiposo/química , Adulto , Ácido Araquidónico/administración & dosificación , Estudios Cruzados , Eritrocitos/química , Humanos , MasculinoRESUMEN
The consequences of a 42 d exposure to elevated growth hormone (GH) on adipose tissue were assessed using the regulatable ovine metallothionein- ovine GH (oMt1a-oGH) transgene in male and female GH transgenic (TG) mice. Activation of transgene expression at 21 d of age followed by inactivation of transgene expression at 63 d of age (TG-on/off) increased individual white adipose tissue (WAT) depots and total body lipid stores in both males and females. WAT, expressed as a percentage of fasted body weight, did not differ in wildtype (WT) and continuously activated TG males and females up to 105 d of age, but was increased approximately 270% following inactivation of the transgene. Inguinal depot adipocytes were more numerous in both male and female TG +/- relative to WT or TG animals. The ensuring obesity was not accompanied by a decrease in thermogenic capacity of brown adipose tissue, as indexed by uncoupling protein quantity. GH transgene expression was accompanied by elevated insulin levels that were restored to WT levels upon cessation of transgene expression (p > 0.1). Early, transient exposure to elevated GH increased total body lipid by nearly threefold independent of gender; the increased lipid content was sustained and reflected WAT hypertrophy and hyperplasia. The oMt1a-oGH mouse provides a novel model of induced obesity in response to inactivation of a GH-transgene by the withdrawal of the transgene stimulus.
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Composición Corporal/fisiología , Hormona del Crecimiento/fisiología , Ratones Transgénicos/fisiología , Adipocitos/química , Adipocitos/citología , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Tejido Adiposo Pardo/citología , Tejido Adiposo Pardo/metabolismo , Animales , Glucemia/metabolismo , Composición Corporal/genética , Peso Corporal/genética , Peso Corporal/fisiología , Proteínas Portadoras/metabolismo , Recuento de Células , Ingestión de Energía/genética , Ingestión de Energía/fisiología , Ayuno , Femenino , Expresión Génica/genética , Regulación de la Expresión Génica/genética , Genotipo , Ingle , Hormona del Crecimiento/sangre , Hormona del Crecimiento/genética , Insulina/sangre , Insulina/genética , Resistencia a la Insulina/genética , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Obesidad/genética , Obesidad/fisiopatología , Fenotipo , Ovinos , Factores de Tiempo , Transgenes/genética , Aumento de Peso/genética , Aumento de Peso/fisiologíaAsunto(s)
Proteínas/metabolismo , Caracteres Sexuales , Adulto , Femenino , Humanos , Leptina , Masculino , Persona de Mediana Edad , Obesidad/metabolismoRESUMEN
Arachidonic acid is an important regulator of cellular function via its effects on the physical properties of membranes, in its free form, or as a substrate for eicosanoids. Dietary studies indicate that its production is regulated, but the mechanisms of this regulation and factors influencing arachidonate distribution from the site of production remain to be determined. In particular, whether there is a nonoxidative fate for arachidonate once it has been released from phospholipid has yet to be determined. Variations in the arachidonate content of serum, liver, and muscle lipid fractions have been correlated with alterations in lipogenesis and insulin action, implying a role for arachidonate in fuel partitioning. Evidence for this mechanism acting systemically has been found in genetic models of obesity in rodents and also in humans. This review proposes that variation in the distribution of arachidonate between phospholipid and cholesteryl ester fractions participates in the abnormal fuel partitioning associated with some forms of genetic obesity.
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Ácido Araquidónico/metabolismo , Obesidad/metabolismo , Animales , Grasas Insaturadas en la Dieta/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados/metabolismo , Humanos , Metabolismo de los Lípidos , Lípidos/biosíntesis , Modelos Genéticos , Obesidad/genética , Ratas , Ratas ZuckerRESUMEN
Growth hormone (GH) has many metabolic effects, but its mechanism(s) of action are not fully understood. We studied the short-term effects of endogenously produced GH on liver delta 6-desaturase activity and adipose and liver lipid fraction fatty acid composition in transgenic mice. MG101 transgenic mice ages 73-114 d received zinc to activate the ovine GH transgene for 7 d. Nontransgenic littermates, used as controls, also received zinc. Liver lipids were fractionated into phospholipids (PL), cholesteryl esters, and triglycerides (TG), and retroperitoneal adipose fractionated into PL and TG for fatty acid analysis. Liver microsomes were assayed for delta 6-desaturase activity. Animals expressing the ovine growth hormone transgene had a 2.5-fold higher liver delta 6-desaturase activity than controls. Arachidonate and docosahexaenoate were significantly higher in liver PL of GH transgenic animals compared to controls, but both were decreased in adipose PL in the GH animals. We conclude that increased production of GH affects both production and organ distribution of highly unsaturated fatty acids. The changes in arachidonate in various lipid pools following transgene expression may mediate the systemic actions of GH.
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Ácido Graso Desaturasas/metabolismo , Expresión Génica , Hormona del Crecimiento/genética , Microsomas Hepáticos/enzimología , Tejido Adiposo/metabolismo , Animales , Ésteres del Colesterol/metabolismo , Ácidos Grasos/metabolismo , Femenino , Linoleoil-CoA Desaturasa , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Ratones , Ratones Transgénicos , Fosfolípidos/metabolismo , Ovinos/genética , Triglicéridos/metabolismo , Zinc/farmacologíaRESUMEN
Protein-calorie malnutrition as evidenced by loss of weight or of lean body mass is a commonly seen disorder. Although its cause is clearly multifactorial, objective measures of protein-calorie malnutrition have been repeatedly correlated with poor patient outcomes. Total parenteral nutrition was developed to halt or reverse this disorder, but its ability to improve the short- to intermediate-term outcome in patients with impaired nutrient intake has been highly inconsistent. Factors influencing this variable outcome include the degree of functional impairment in the treatment group, the underlying disease causing the impaired intake, and possibly the amount and composition of nonprotein calories delivered. In particular, considerable evidence points to intravenous soybean oil emulsion as a negative factor in the nutritional support of stressed patients. Taken in combination, current information suggests reserving the use of parenteral feeding for patients meeting objective criteria for protein-calorie malnutrition and making parsimonious use of lipid emulsion, especially in stressed patients.
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Nutrición Parenteral Total , Desnutrición Proteico-Calórica/terapia , Humanos , Evaluación Nutricional , Resultado del TratamientoRESUMEN
Epidemiologic evidence in humans and controlled trials in animal models indicate that total dietary fat increases the risk of cancer. The animal evidence indicates that the greatest efficacy in promoting carcinogenesis is achieved with omega-6 fatty acids with little or no effect from either the omega-3 or monounsaturated fatty acid families. Epidemiologic studies in humans indicate a positive association between meat intake and colon cancer, but a negative association with chicken and fish. There is also a negative association between non-steroidal anti-inflammatory drug (NSAID) intake and colon cancer. Red meat is a potentially significant source of dietary arachidonic acid, which is the primary substrate for the eicosanoids whose production is blocked by NSAIDs. Thus there is a positive association between carcinogenesis and dietary intake of both the omega-6 fatty acid precursor linoleic acid and its product arachidonic acid, and a negative association with use of a drug blocking its metabolism to eicosanoids. Another potentially important factor in arachidonate metabolism is variation in its endogenous distribution. We have recently reported abnormal distribution of arachidonic acid between lipid fractions in human obesity, and parallel abnormalities in animal models of genetic obesity. This implies a potential role for variation in the endogenous distribution of arachidonic acid in the etiology of cancers which have increased incidence in human obesity. This paper addresses the role of arachidonate intake, its endogenous production, and its distribution within lipid fractions in carcinogenesis.
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Ácido Araquidónico/metabolismo , Neoplasias/metabolismo , Animales , Ácido Araquidónico/administración & dosificación , Ácidos Grasos , Humanos , Obesidad/metabolismo , Terminología como AsuntoRESUMEN
Adipose tissue was obtained from six women undergoing liposuction twice at 6-mo intervals. Samples obtained bilaterally from abdomen, inner thigh, and outer thigh had fatty acids quantified by gas chromatography. There were no important differences between sides or over time. The saturates 14:0, 16:0, 18:0, and 20:0 were higher in abdominal adipose than in outer thigh (P < 0.002 for all); 16:1 and 18:1 omega 9 were lower in abdomen vs outer thigh (P < 0.01), whereas 18:1 omega 7 and 20:1 omega 9 were unchanged. Polyunsaturates 18:2 omega 6, 20:3 omega 6, and 20:4 omega 6 were higher in outer thigh than in abdomen (P < 0.06), and inner thigh values were intermediate. These changes in fatty acid composition resulted in lower mean triglyceride melting points from abdomen to inner thigh to outer thigh, and suggest that temperature may influence the selection process determining the variation in adipose fatty acid composition with anatomical location. Because the site-specific differences included essential fatty acids, selective uptake as well as potential differences in in situ fatty acid modification are indicated.
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Abdomen , Tejido Adiposo/química , Ácidos Grasos/análisis , Muslo , Adulto , Análisis de Varianza , Femenino , Humanos , Lipectomía , Persona de Mediana EdadRESUMEN
To determine whether there is altered liver lipid-fraction fatty acid distribution in a multigenic obese mouse model, we examined livers from eight lean (0.2-4.2% carcass fat), seven intermediate (5.7-13.8%), and five obese (20.2-48.7%) backcross progeny [(C57BL/6J x Mus spretus) x C57BL/6J] aged 2-3 mo. Thirteen males and seven females were fed a nonpurified stock diet. Liver lipid fractions were separated and fatty acids quantitated by thin-layer and gas chromatography. There was a significant effect of obesity on 18:2 omega 6 in liver phospholipids (PL), cholesteryl esters, and triglycerides. PL 18:2 omega 6 was negatively correlated with carcass fat (r = -0.74, P < 0.001); 20:3 omega 6 was elevated in PL with increased obesity (P < 0.0001), and was correlated with carcass fat (r = 0.92, P < 0.0001); and 20:4 omega 6 in PL did not differ with obesity status. PL 20:3 omega 6 and 20:4 omega 6 were lower in males (P < 0.01 and 0.02, respectively) than in females. We conclude that obesity and sex affect distribution of omega 6 essential fatty acids in mouse liver lipid fractions.
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Ácidos Grasos Esenciales/metabolismo , Hígado/metabolismo , Obesidad/metabolismo , Animales , Composición Corporal , Peso Corporal , Ésteres del Colesterol/análisis , Ésteres del Colesterol/metabolismo , Cromatografía de Gases , Cromatografía en Capa Delgada , Ácidos Grasos Esenciales/análisis , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados/análisis , Ácidos Grasos Insaturados/metabolismo , Femenino , Hígado/química , Masculino , Ratones , Ratones Obesos , Modelos Biológicos , Obesidad/genética , Fosfolípidos/análisis , Fosfolípidos/metabolismo , Factores Sexuales , Triglicéridos/análisis , Triglicéridos/metabolismoRESUMEN
The micropig model of chronic alcoholism was used to study the relationship of lipid composition and physical properties in three different tissue membranes from the same animals. Ethanol feeding reduced membrane anisotropy, as measured with the diphenylhexatriene probe, in liver plasma and kidney brush-border membranes but not in jejunal brush-border membranes. Preincubation with ethanol reduced anisotropy in each of the three control membranes, whereas all three membranes from the ethanol-fed group were relatively tolerant to the acute effect of ethanol. In liver and kidney membranes, ethanol feeding increased levels of linoleic (18:2 omega 6) acid and decreased levels of arachidonic (20:4 omega 6) and docosahexaenoic (22:6 omega 3) acids and their specific double-bond positions, consistent with reduced activities of delta 6 and delta 5 fatty acid desaturases. In liver and kidney membranes, anisotropy parameters and the acute effect of ethanol correlated inversely with levels of linoleic acid and directly with levels of arachidonic and docosahexaenoic acids and their specific double bonds. Levels of docosahexaenoic acid correlated with the acute effect of ethanol in all three membranes. Phospholipid fatty acid profiles were similar in jejunal brush-border membranes and terminal bile samples, suggesting that the effects of ethanol on jejunal fatty acids and physical properties are modulated by intraluminal biliary phospholipids. The effect of ethanol on anisotropy could not be attributed to changes in membrane cholesterol/phospholipid ratios. These studies affirm the value of this new animal model of chronic alcoholism and provide comprehensive evidence for the central role of fatty acid desaturation in the membrane-associated effects of ethanol exposure.