RESUMEN
Type-1 diabetes mellitus (T1DM) is associated with metabolic changes leading to alterations in glucose and lipid handling. While T1DM-associated effects on many major plasma lipids have been characterised, such effects on plasma free fatty acids (FFA) have not been fully examined. Using gas chromatography-mass spectrometry, we measured the plasma concentrations of FFA species in individuals with T1DM (n = 44) and age/sex-matched healthy controls (n = 44). Relationships between FFA species and various parameters were evaluated. Plasma concentrations of myristate (14:0), palmitoleate (16:1), palmitate (16:0), linoleate (18:2), oleate (18:1c9), cis-vaccenate (18:1c11), eicosapentaenoate (20:5), arachidonate (20:4) and docosahexanoate (22:6) were reduced in the T1DM group (p < 0.0001 for all, except p = 0.0020 for eicosapentaenoate and p = 0.0068 for arachidonate); α-linolenate (18:3) and dihomo-γ-linolenate (20:3) concentrations were unchanged. The saturated/unsaturated FFA ratio, n-3/n-6 ratio, de novo lipogenesis index (palmitate (main lipogenesis product)/linoleate (only found in diet)) and elongase index (oleate/palmitoleate) were increased in the T1DM group (p = 0.0166, p = 0.0089, p < 0.0001 and p = 0.0008 respectively). The stearoyl-CoA desaturase 1 (SCD1) index 1 (palmitoleate/palmitate) and index 2 (oleate/stearate) were reduced in T1DM (p < 0.0001 for both). The delta-(5)-desaturase (D5D) index (arachidonate/dihomo-γ-linolenate) was unchanged. Age and sex had no effect on plasma FFA concentrations in T1DM, while SCD1 index 1 was positively correlated (p = 0.098) and elongase index negatively correlated with age (p = 0.0363). HbA1c was negatively correlated with all plasma FFA concentrations measured except α-linolenate and dihomo-γ-linolenate. Correlations were observed between plasma FFA concentrations and cholesterol and HDL concentrations, but not LDL concentration or diabetes duration. Collectively, these results aid our understanding of T1DM and its effects on lipid metabolism.
Asunto(s)
HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 1/sangre , Ácidos Grasos no Esterificados/sangre , Metabolismo de los Lípidos/genética , Triglicéridos/sangre , Adolescente , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patología , Ayuno/sangre , Ácidos Grasos no Esterificados/clasificación , Femenino , Expresión Génica , Hemoglobina Glucada/genética , Hemoglobina Glucada/metabolismo , Humanos , Lipidómica/métodos , Masculino , Albúmina Sérica Humana/metabolismo , Estearoil-CoA Desaturasa/sangre , Estearoil-CoA Desaturasa/genéticaRESUMEN
BACKGROUND: The aim was to investigate if fatty acid profile and estimated desaturase activities; stearoyl CoA-desaturase (SCD), delta-5-desaturase and delta-6-desaturase (D5D; D6D), differ between individuals with metabolically healthy (MH) and unhealthy (MU) phenotypes. We also explored these associations according to BMI categories. METHODS: Men and women at moderately elevated risk of cardiovascular disease were included in this cross-sectional study (n = 321). If subjects met ≥4 out of 5 criteria (elevated triglycerides, total and LDL-cholesterol, HbA1c and low HDL-cholesterol), they were classified as MU (n = 52). If levels were within reference ranges for ≥3 of the same criteria, subjects were classified as MH (n = 150). Utilizing the entire population, a score ranging from 0 to 5 denoting the number of MU criteria met was computed. Estimated desaturase activities were calculated as product-to-precursor ratio of fatty acids in whole blood (SCD16 [16:1n7/16:0], SCD18 [18:1n9/18:0], D5D [18:3n6/18:2n6], D6D [20:4n6/20:3n6]). RESULTS: Individuals with MH had lower estimated SCD16 and SCD18 activities, whereas estimated D6D activity was higher compared to MU. Similar, SCD16 and SCD18 increased, whereas D6D decreased with increasing criteria of MU. Trends were similar across BMI categories. CONCLUSIONS: This study supports the notion of estimated desaturase activities as possible novel biomarkers of metabolic health irrespectively of BMI.
Asunto(s)
LDL-Colesterol/sangre , Ácido Graso Desaturasas/sangre , Síndrome Metabólico/sangre , Estearoil-CoA Desaturasa/sangre , Triglicéridos/sangre , Anciano , Estudios Transversales , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/metabolismo , Ácidos Grasos/metabolismo , Femenino , Humanos , Masculino , Síndrome Metabólico/enzimología , Persona de Mediana Edad , Estearoil-CoA Desaturasa/metabolismoRESUMEN
BACKGROUND: Elevated stearoyl-CoA desaturase 1 (SCD-1) activity showed associations with obesity in cross-sectional studies. In non-pregnant populations, nutrition regulates SCD-1 transcription and activity. OBJECTIVE: To investigate the longitudinal associations of maternal and fetal SCD-1 activity markers with infant anthropometry up to 2 years of age, and to explore how selected dietary intakes modulate SCD-1 activity in pregnancy. METHODS: As a secondary analysis from the ROLO intervention study, which was conducted in a population at risk for macrosomia, non-esterified fatty acids (NEFA) from maternal plasma at 13 and 28 weeks' gestation and in cord blood were measured via liquid-chromatography-mass-spectrometry. Fatty acid ratios 18:1/18:0 and 16:1/16:0 were used as markers for SCD-1 activity ('desaturation indices', DIs). Relationships of DIs with infant anthropometry up to 2 years of age and maternal dietary parameters during pregnancy were investigated using adjusted linear regression models and p-values correction for multiple testing. RESULTS: 18:1/18:0, but not 16:1/16:0, was associated with measures of infant anthropometry at birth (maternal and fetal markers) and up to 2 years of age (maternal markers only). Dietary intakes did not show strong associations with 18:1/18:0, but 16:1/16:0 was associated with absolute and relative dietary intakes. CONCLUSIONS: In a population at risk for macrosomia, maternal SCD-1 activity measured via 18:1/18:0 was involved in the fetal programming of infant obesity, but could not be substantially modulated by short-term diet in pregnancy. CLINICAL TRIAL REGISTRATION: ISRCTN Registration number: ISRCTN54392969 (http://www.isrctn.com/ISRCTN54392969).
Asunto(s)
Desarrollo Infantil , Dieta , Ácidos Grasos/sangre , Sangre Fetal/enzimología , Fenómenos Fisiologicos Nutricionales Maternos , Obesidad Infantil/etiología , Efectos Tardíos de la Exposición Prenatal , Estearoil-CoA Desaturasa/sangre , Adiposidad , Adulto , Factores de Edad , Antropometría , Biomarcadores/sangre , Preescolar , Femenino , Humanos , Recién Nacido , Estudios Longitudinales , Obesidad Infantil/sangre , Obesidad Infantil/enzimología , Obesidad Infantil/fisiopatología , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de RiesgoRESUMEN
We previously reported that triglyceride (TG) levels in small-for-gestational age (SGA) newborns were significantly higher than those in appropriate-for-gestational age (AGA) newborns. Stearoyl-CoA desaturase (SCD) activity is required for TG synthesis, while lipoprotein lipase mass (LPLm) facilitates TG clearance. The purpose of this study is to reveal whether SCD activity or LPLm is the cause of high TG levels in SGA newborns. Fifty-five newborns were classified as AGA (nâ¯=â¯42) and SGA (nâ¯=â¯13). Serum LPLm, TG and fatty acids in umbilical cord blood were analyzed. Then, [16:1 (n-7)]/ [16:0] and [18:1 (n-9)]/ [18:0] were calculated as SCD16 and SCD18 activities, respectively. The SGA group showed significantly higher TG levels and significantly lower LPLm levels than the AGA group. However, SCD16 and 18 activities were lower in SGA newborns than in AGA newborns. In conclusion, LPLm, rather than SCD activity may be involved in the increased TG levels in SGA newborns.
Asunto(s)
Sangre Fetal/enzimología , Recién Nacido Pequeño para la Edad Gestacional/sangre , Lipoproteína Lipasa/sangre , Estearoil-CoA Desaturasa/sangre , Adulto , Femenino , Edad Gestacional , Humanos , Recién Nacido , MasculinoRESUMEN
RATIONALE: In black women, triglycerides are paradoxically normal in the presence of insulin resistance. This relationship may be explained by race-related differences in central adiposity and SCD (stearoyl-CoA desaturase)-1 enzyme activity index. OBJECTIVE: In a cross-sectional study, to compare fasting and postprandial triglyceride-rich lipoprotein particle (TRLP) concentrations and size in black compared with white pre- and postmenopausal women and determine the relationship between TRLP subfractions and whole-body insulin sensitivity, hepatic and visceral fat, and SCD-1 levels. METHODS AND RESULTS: In 122 federally employed women without diabetes mellitus, 73 black (58 African American and 15 African immigrant) and 49 white; age, 44±10 (mean±SD) years; body mass index, 30.0±5.6 kg/m2, we measured lipoprotein subfractions using nuclear magnetic resonance. Hepatic fat was measured by proton magnetic resonance spectroscopy, insulin sensitivity index calculated by minimal modeling from a frequently sampled intravenous glucose test, and red blood cell fatty acid profiles were measured by gas chromatography and were used to estimate SCD-1 indices. Hepatic fat, insulin sensitivity index, and SCD-1 were similar in black women and lower than in whites, regardless of menopausal status. Fasting and postprandial large, medium, and small TRLPs, but not very small TRLPs, were lower in black women. Fasting large, medium, and very small TRLPs negatively correlated with insulin sensitivity index and positively correlated with visceral and hepatic fat and SCD-1 activity in both groups. In multivariate models, visceral fat and SCD-1 were associated with total fasting TRLP concentrations (adjR2, 0.39; P=0.001). Black women had smaller postprandial changes in large (P=0.005) and medium TRLPs (P=0.007). CONCLUSIONS: Lower visceral fat and SCD-1 activity may contribute to the paradoxical association of lower fasting and postprandial TRLP subfractions despite insulin resistance in black compared with white pre- and postmenopausal women. Similar concentrations of very small TRLPs are related to insulin resistance and could be important mediators of cardiometabolic disease risk in women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01809288.
Asunto(s)
Adiposidad/etnología , Población Negra , Diabetes Mellitus Tipo 2/etnología , Resistencia a la Insulina/etnología , Lipoproteínas/sangre , Obesidad/etnología , Estado Prediabético/etnología , Estearoil-CoA Desaturasa/fisiología , Triglicéridos/sangre , Población Blanca , Adulto , África/etnología , Negro o Afroamericano , Glucemia/metabolismo , Estudios Transversales , Susceptibilidad a Enfermedades , Emigrantes e Inmigrantes , Ingestión de Energía , Ayuno/sangre , Femenino , Humanos , Resistencia a la Insulina/fisiología , Grasa Intraabdominal/anatomía & histología , Hígado/anatomía & histología , Menopausia , Persona de Mediana Edad , Periodo Posprandial , Estearoil-CoA Desaturasa/sangreRESUMEN
The fatty acid (FA) composition of red blood cell (RBC) membrane phospholipids of cancer patients can reflect tumor status, dietary intakes, and cancer type or therapy. However, the characteristic membrane profiles have so far not yet defined as a potential biomarker to monitor disease evolution. The present work provides the first evidence of cancer metabolic signatures affecting cell membranes that are independent of nutritional habits. From the Oncology Outpatient Unit of the Onkologikoa hospital, two groups of cancer patients (n = 54) and healthy controls (n = 37) were recruited, and mature RBCs membrane phospholipids were analyzed for FA profiling (GC-MS). Dietary habits were evaluated using a validated food frequency questionnaire. The adjusted Analysis of Covariance Test (ANCOVA) model revealed cancer patients to have a lower relative percentage of saturated fatty acids (SFA) (C16:0 (5.7%); C18:0 (15.9%)), and higher monounsaturated fatty acids (MUFA) (9c-C18:1 (12.9%) and 11c-C18:1 (54.5%)), compared to controls. In line with this, we observe that the desaturase enzymatic index (delta-9 desaturase (Δ9D), +28.3%) and the membrane saturation index (SI = SFA/MUFA; -27.3%) were similarly modulated. Polyunsaturated fatty acids (PUFA) families showed an increase of n-6 C18:2 and C20:3 (15.7% and 22.2% respectively), with no differences in n-6 C20:4 and n-3 PUFA (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)). Importantly, these changes were found independent of foods and fat intakes from the diet. The membrane lipid profile in RBC was useful to ascertain the presence of two main metabolic signatures of increased desaturation activity and omega-6 in cancer patients, statistically independent from dietary habits.
Asunto(s)
Membrana Eritrocítica/metabolismo , Ácidos Grasos Monoinsaturados/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Neoplasias/metabolismo , Fosfolípidos/sangre , Adulto , Encuestas sobre Dietas , Ácidos Grasos , Ácidos Grasos Insaturados/sangre , Conducta Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estearoil-CoA Desaturasa/sangreRESUMEN
Glucocorticoid treatment decreases liver insulin sensitivity and may modify fatty acid metabolism. We investigated the influence of oral prednisolone on indices for de novo lipogenesis (DNLi), stearoyl-CoA desaturase (SCDi) and Δ6-desaturase (D6Di) activity in healthy males. In addition, we explored whether the changes may be associated with prednisolone-induced changes in glucose and lipid metabolism and insulin sensitivity. Thirty-two healthy young males (mean⯱â¯SD age 22⯱â¯3 years, BMI 22.4⯱â¯1.7â¯kg/m2) were allocated to receive prednisolone 7.5â¯mg/day (PRED7.5; nâ¯=â¯12), prednisolone 30â¯mg/day (PRED30; nâ¯=â¯12), or placebo (nâ¯=â¯8) in a randomized double-blind fashion for 2 weeks. Fatty acid compositions of plasma cholesteryl esters (CE), phospholipids (PL) and triglycerides (TG) were measured at baseline and on day 14. DNLi, SCDi and D6Di were estimated from product/precursor ratios in CE, with DNLi primary deriving from 16:1ω7/18:2ω6, SCDi from 16:1ω7/16:0 and D6Di from 22:6ω3/20:5ω3. Ratios were also assessed in PL and TG. In CE, PRED30 increased DNLi by 51.2 [95%CI 14.8; 87.6]%, increased SCDi by 48.6 [18.7; 78.5]%, and decreased D6Di by 57.7 [-91.8; -23.5]% (pâ¯≤â¯0.01 for all, compared to placebo). The prednisolone-induced increases in DNLi and SCDi were positively correlated with insulin sensitivity (râ¯=â¯0.35 and 0.50, respectively). Similar results were found in PL and TG. Prednisolone dose-dependently increases DNLi and SCDi and decreases D6Di in plasma CE, PL and TG in healthy males after 2 weeks. The observed unfavorable effects on fatty acid metabolism were related to the induction of glucocorticoid-induced insulin resistance.
Asunto(s)
Antiinflamatorios/farmacología , Linoleoil-CoA Desaturasa/genética , Metabolismo de los Lípidos/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Prednisolona/farmacología , Estearoil-CoA Desaturasa/genética , Administración Oral , Adulto , Glucemia/efectos de los fármacos , Ésteres del Colesterol/sangre , Método Doble Ciego , Esquema de Medicación , Expresión Génica , Voluntarios Sanos , Humanos , Resistencia a la Insulina , Linoleoil-CoA Desaturasa/sangre , Metabolismo de los Lípidos/genética , Lipogénesis/genética , Masculino , Fosfolípidos/sangre , Estearoil-CoA Desaturasa/sangre , Triglicéridos/sangreRESUMEN
We hypothesized that consumption of saturated fatty acids in the form of high-fat ground beef for 5 weeks would depress liver X receptor signaling targets in peripheral blood mononuclear cells (PBMC) and that changes in gene expression would be associated with the corresponding changes in lipoprotein cholesterol (C) concentrations. Older men (n = 5, age 68.0 ± 4.6 years) and postmenopausal women (n = 7, age 60.9 ± 3.1 years) were assigned randomly to consume ground-beef containing 18% total fat (18F) or 25% total fat (25F), five patties per week for 5 weeks with an intervening 4-week washout period. The 25F and 18F ground-beef increased (p < 0.05) the intake of saturated fat, monounsaturated fat, palmitic acid, and stearic acid, but the 25F ground-beef increased only the intake of oleic acid (p < 0.05). The ground-beefs 18F and 25F increased the plasma concentration of palmitic acid (p < 0.05) and decreased the plasma concentrations of arachidonic, eicosapentaenoic, and docosahexaenic acids (p < 0.05). The interventions of 18F and 25F ground-beef decreased very low-density lipoprotein C concentrations and increased particle diameters and low-density lipoprotein (LDL)-I-C and LDL-II-C concentrations (p < 0.05). The ground-beef 25F decreased PBMC mRNA levels for the adenosine triphosphate (ATP) binding cassette A, ATP binding cassette G1, sterol regulatory element binding protein-1, and LDL receptor (LDLR) (p < 0.05). The ground-beef 18F increased mRNA levels for stearoyl-CoA desaturase-1 (p < 0.05). We conclude that the increased LDL particle size and LDL-I-C and LDL-II-C concentrations following the 25F ground-beef intervention may have been caused by decreased hepatic LDLR gene expression.
Asunto(s)
Dieta Alta en Grasa , Leucocitos Mononucleares/metabolismo , Receptores X del Hígado/genética , Carne Roja/análisis , Transportador 1 de Casete de Unión a ATP/sangre , Transportador 1 de Casete de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/sangre , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Anciano , Animales , Ácido Araquidónico/sangre , Bovinos , Estudios Cruzados , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Femenino , Regulación de la Expresión Génica , Humanos , Leucocitos Mononucleares/citología , Lipoproteínas LDL/sangre , Receptores X del Hígado/sangre , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Ácido Palmítico/sangre , Receptores de LDL/sangre , Receptores de LDL/genética , Ácidos Esteáricos/sangre , Estearoil-CoA Desaturasa/sangre , Estearoil-CoA Desaturasa/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/sangre , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
BACKGROUND: Significant associations between visceral fat and alterations in plasma fatty acids have been identified in overweight individuals. However, there are scant data regarding the relationships of the visceral fat area (VFA) with the plasma fatty acid profiles and desaturase activities following weight loss. We investigated the effect of weight loss with mild calorie restriction on the circulating fatty acid profiles and desaturase activities in nondiabetic overweight subjects with high VFA. METHODS: Eighty overweight subjects with high VFA (L4 VFA ≥100 cm2) were randomized into the 12-week mild-calorie-restriction (300 kcal/day) or control groups. RESULTS: Comparison of the percent of body weight changes between groups revealed that the weight-loss group had greater reductions in body weight. The VFA decreased by 17.7 cm2 from baseline in the weight-loss group (P < 0.001). At follow-up, the weight-loss group showed greater reductions in serum triglycerides, insulin, and HOMA-IR than the control group. Significantly greater reductions in total saturated fatty acids, palmitic acid, stearic acid, total monounsaturated fatty acids, palmitoleic acid, oleic acid, eicosadienoic acid, and dihomo-γ-linolenic acid levels were detected in the weight-loss group compared with the control group after adjusting for baseline values. Following weight loss, C16 Δ9-desaturase activity was significantly decreased and Δ5-desaturase activity was significantly increased, and the changes were greater in the weight-loss group than in the control group. CONCLUSIONS: The results suggest that mild weight loss improves abdominal obesity, overall fatty acid profiles, and desaturase activities; therefore, mild calorie restriction has potential health benefits related to obesity-related diseases in overweight subjects with high VFA. TRIAL REGISTRATION: NCT02992639. Retrospectively registered 11 December 2016.
Asunto(s)
Ácidos Grasos/sangre , Grasa Intraabdominal/fisiopatología , Sobrepeso/fisiopatología , Pérdida de Peso/fisiología , Adulto , Composición Corporal , Índice de Masa Corporal , Restricción Calórica , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/sangre , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Sobrepeso/sangre , Placebos , Estearoil-CoA Desaturasa/sangre , Triglicéridos/sangreRESUMEN
BACKGROUND & AIMS: The activity of stearoyl-CoA desaturase-1 (SCD1), the central enzyme in the synthesis of monounsaturated fatty acids (MUFA), has been associated with de novo lipogenesis. In experimental models SCD1 is down-regulated by polyunsaturated fatty acids (PUFA), but clinical studies are scarce. The effect of long-chain n-3 PUFA (LCn-3PUFA) supplied by the regular diet, in the absence of fatty fish or fish oil supplementation, remains to be explored. METHODS: We related 1-y changes in plasma SCD1 index, as assessed by the C16:1n-7/C16:0 ratio, to both adiposity traits and nutrient intake changes in a sub-cohort (n = 243) of non-hypertriglyceridemic subjects of the PREDIMED (PREvención con DIeta MEDiterranea) trial. RESULTS: After adjustment for confounders, including changes in fasting triglycerides, plasma SCD1 index increased in parallel with body weight (0.221 [95% confidence interval, 0.021 to 0.422], P = 0.031) and BMI (0.115 [0.027 to 0.202], P = 0.011). Additionally, dietary LCn-3PUFA (but not MUFA or plant-derived PUFA) were associated with decreased plasma SCD1 index (-0.544 [-1.044 to -0.043], P = 0.033, for each 1 g/d-increase in LCn-3PUFA). No associations were found for other food groups, but there was a trend for fatty fish intake (-0.083 [-0.177 to 0.012], P = 0.085, for each 10 g/d-increase). CONCLUSIONS: Our data add clinical evidence on the down-regulation of plasma SCD1 index by LCn-3PUFA in the context of realistic changes in fish consumption in the customary, non-supplemented diet. CLINICAL TRIAL REGISTRATION: http://www.Controlled-trials.com/ISRCTN35739639.
Asunto(s)
Encuestas sobre Dietas , Dieta Mediterránea/estadística & datos numéricos , Ácidos Grasos Omega-3/metabolismo , Estearoil-CoA Desaturasa/sangre , Anciano , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Humanos , Hipertensión , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: We describe body composition, lipid metabolism and Stearoyl-CoA desaturase-1 (SCD-1) indices in patients with classical homocystinuria (HCU). METHODS: Eleven treated HCU patients and 16 healthy controls were included. Body composition and bone mineral density were assessed by dual X-ray absorptiometry. Sulfur amino acids (SAA) and their derivatives (total homocysteine, cysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, and glutathione), lipids (free fatty acids, acylcarnitines, triglycerides and lipoproteins), glucose, insulin, leptin, adiponectin, and isoprostanes were measured in plasma. Insulin resistance was evaluated by HOMA-IR. To estimate liver SCD-1 activity, SCD-16 [16:1(n-7)/16:0] and SCD-18 [18:1(n-9)/18:0] desaturation indices were determined. RESULTS: In HCU patients, SCD-16 index was significantly reduced (p=0.03). A trend of an association of SCD-16 index with cysteine was observed (r=0.624, p=0.054). HCU patients displayed lower lean mass (p<0.05), with no differences in fat mass percentage. Leptin and low-density lipoprotein concentrations were lower in HCU patients (p<0.05). Femur bone mineral density Z-scores were correlated with plasma cysteine (r=0.829; p=0.04) and total homocysteine (r=-0.829; p=0.04) in HCU patients. CONCLUSIONS: We report alterations in leptin and SCD-1 in HCU patients. These results agree with previous findings from epidemiologic and animal studies, and support a role for SAA on lipid homeostasis.
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Aminoácidos Sulfúricos/sangre , Homocistinuria/sangre , Leptina/sangre , Metabolismo de los Lípidos , Estearoil-CoA Desaturasa/sangre , Adulto , Densidad Ósea , Femenino , Homocistinuria/metabolismo , Homocistinuria/fisiopatología , Humanos , Masculino , Adulto JovenRESUMEN
The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1ß (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.
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Ácidos Grasos/sangre , Polimorfismo de Nucleótido Simple , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Adolescente , Adulto , Alelos , Biomarcadores/sangre , Brasil , Niño , Colesterol/sangre , Estudios Transversales , Ejercicio Físico , Ácidos Grasos Monoinsaturados/sangre , Femenino , Técnicas de Genotipaje , Humanos , Interleucinas/sangre , Modelos Logísticos , Masculino , Persona de Mediana Edad , Ácido Oléico/sangre , Ácidos Esteáricos/sangre , Estearoil-CoA Desaturasa/sangre , Estearoil-CoA Desaturasa/genética , Encuestas y Cuestionarios , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto Joven , Ácido alfa-Linolénico/sangreRESUMEN
OBJECTIVE: The aim of this study was to investigate the interaction of toll-like receptor 4 (TLR4) gene single nucleotide polymorphism (SNP) and plasma fatty acid (FA) profile in modulating risk for systemic inflammation. METHODS: In all, 262 adult (19-59 y) participants of the Health Survey of São Paulo met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and four SNPs of the TLR4 gene (rs4986790, rs4986791, rs11536889, and rs5030728) were genotyped. Multivariate cluster analysis was performed to stratify individuals based on levels of 11 plasma inflammatory biomarkers into two groups: inflammatory (INF) and noninflammatory (NINF). RESULTS: No association was found between any of the SNPs studied and systemic inflammation. The INF cluster had higher palmitic acid levels (P = 0.039) and estimated stearoyl coenzyme A desaturase activity (P = 0.045) and lower polyunsaturated fatty acid (P = 0.011), ω-6 fatty acid (P = 0.018), arachidonic acid (P = 0.002) levels, and estimated δ-5 desaturase activity (P = 0.025) compared with the NINF cluster. Statistically significant interaction between rs11536889 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio (P = 0.034) was found to increase the odds of belonging to the INF cluster when individuals had the variant allele C and were at the higher percentile of AA/EPA plasma ratio. CONCLUSION: Plasma fatty acid profile modulated the odds of belonging to the INF cluster depending on genotypes of TRL4 gene polymorphisms.
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Ácidos Grasos/sangre , Inflamación/sangre , Inflamación/genética , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 4/genética , Adulto , Presión Sanguínea , Índice de Masa Corporal , Estudios Transversales , delta-5 Desaturasa de Ácido Graso , Ácido Graso Desaturasas/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Femenino , Humanos , Modelos Logísticos , Masculino , Recuerdo Mental , Análisis de Secuencia de ADN , Estearoil-CoA Desaturasa/sangre , Receptor Toll-Like 4/metabolismo , Triglicéridos/sangre , Circunferencia de la Cintura , Adulto JovenRESUMEN
BACKGROUND/OBJECTIVES: Conversion of saturated fatty acids to monounsaturated fatty acids by the enzyme stearoyl-Co-A-desaturase (SCD-1) is emerging as a major factor in promoting carcinogenesis including breast cancer. The aim of our study was to explore the regulation of SCD-1 by Raloxifene and omega-3 fatty acids in women at increased risk of breast cancer based on high breast density. SUBJECTS/METHODS: As a reflection of SCD-1 activity, we measured the ratios of palmitoleic acid (C16:1n7) to palmitic acid (C16:0) (SCD-16) and oleic acid (C18:1n9) to steric acid (C18:0) (SCD-18) in plasma samples of postmenopausal women enrolled in our clinical trial (NCT00723398) designed to test the effects of the antiestrogen, Raloxifene and/or the omega-3 preparation Lovaza, on breast density, a validated biomarker of breast cancer risk. RESULTS: We report that Lovaza but not Raloxifene-reduced SCD-16 and SCD-18 for the 2-year duration of the trial. Importantly, decreasing levels of SCD-16 and SCD-18 were associated with a progressive reduction in breast density but only in obese women (body mass index ⩾30). CONCLUSIONS: Body mass index-related factors play an important role in the reduction of breast density and hence breast cancer risk by omega-3 fatty acids. SCD-1 may be a useful biomarker in future clinical trials testing the benefit of nutritional interventions in reducing obesity-associated breast cancer risk.
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Densidad de la Mama/efectos de los fármacos , Neoplasias de la Mama/prevención & control , Ácidos Grasos Omega-3/sangre , Obesidad/fisiopatología , Estearoil-CoA Desaturasa/sangre , Adulto , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Neoplasias de la Mama/sangre , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/sangre , Moduladores de los Receptores de Estrógeno/administración & dosificación , Moduladores de los Receptores de Estrógeno/sangre , Ácidos Grasos/sangre , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Monoinsaturados/sangre , Ácidos Grasos Omega-3/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Obesidad/sangre , Ácido Oléico/administración & dosificación , Ácido Oléico/sangre , Ácido Palmítico/administración & dosificación , Ácido Palmítico/sangre , Posmenopausia , Clorhidrato de Raloxifeno/administración & dosificación , Clorhidrato de Raloxifeno/sangre , Factores de RiesgoRESUMEN
Abdominal obesity is a key contributor of metabolic disease. Recent trials suggest that dietary fat quality affects abdominal fat content, where palmitic acid and linoleic acid influence abdominal obesity differently, while effects of n-3 polyunsaturated fatty acids are less studied. Also, fatty acid desaturation may be altered in abdominal obesity. We aimed to investigate cross-sectional associations of serum fatty acids and desaturases with abdominal obesity prevalence in a population-based cohort study. Serum cholesteryl ester fatty acids composition was measured by gas chromatography in 60-year old men (n = 1883) and women (n = 2015). Cross-sectional associations of fatty acids with abdominal obesity prevalence and anthropometric measures (e.g., sagittal abdominal diameter) were evaluated in multivariable-adjusted logistic and linear regression models, respectively. Similar models were employed to investigate relations between desaturase activities (estimated by fatty acid ratios) and abdominal obesity. In logistic regression analyses, palmitic acid, stearoyl-CoA-desaturase and Δ6-desaturase indices were associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals) for highest versus lowest quartiles were 1.45 (1.19-1.76), 4.06 (3.27-5.05), and 3.07 (2.51-3.75), respectively. Linoleic acid, α-linolenic acid, docohexaenoic acid, and Δ5-desaturase were inversely associated with abdominal obesity; multivariable-adjusted odds ratios (95% confidence intervals): 0.39 (0.32-0.48), 0.74 (0.61-0.89), 0.76 (0.62-0.93), and 0.40 (0.33-0.49), respectively. Eicosapentaenoic acid was not associated with abdominal obesity. Similar results were obtained from linear regression models evaluating associations with different anthropometric measures. Sex-specific and linear associations were mainly observed for n3-polyunsaturated fatty acids, while associations of the other exposures were generally non-linear and similar across sexes. In accordance with findings from short-term trials, abdominal obesity was more common among individuals with relatively high proportions of palmitic acid, whilst the contrary was true for linoleic acid. Further trials should examine the potential role of linoleic acid and its main dietary source, vegetable oils, in abdominal obesity prevention.
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Grasas de la Dieta/administración & dosificación , Linoleoil-CoA Desaturasa/sangre , Obesidad Abdominal/sangre , Estearoil-CoA Desaturasa/sangre , Estudios de Cohortes , Estudios Transversales , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Femenino , Expresión Génica , Humanos , Modelos Lineales , Ácido Linoleico/sangre , Linoleoil-CoA Desaturasa/genética , Masculino , Persona de Mediana Edad , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/fisiopatología , Ácido Palmítico/sangre , Estearoil-CoA Desaturasa/genética , Ácido alfa-Linolénico/sangreRESUMEN
Obesity is viewed as a serious public health problem. This study aimed to investigate the antiobesity effects of fermented garlic extract by lactic acid bacteria (LAFGE) on obesity. Male C57BL/6J mice were fed with high-fat diet (HFD) to induce obesity. The HFD-induced obese mice were orally administrated with 250 or 500 mg/kg LAFGE for 8 weeks. Feeding HFD-fed mice with 250 or 500 mg/kg LAFGE reduced body weight by 14% and 18%, respectively, compared to HFD. HFD-fed mice with 500 mg/kg LAFGE administration had lower epididymal, retroperitoneal, and mesenteric adipose tissue mass by 36%, 44%, and 63%, respectively, compared to HFD. The concentration of plasma triacylglyceride and total cholesterol was significantly lower in the HFD-fed mice with LAFGE administration. Moreover, LAFGE supplementation suppressed adipogenesis by downregulation in mRNA and protein expression of PPARγ, C/EBPα, and lipogenic proteins, including SREBP-1c, FAS, and SCD-1. Based on these findings, LAFGE may ameliorate diet-induced obesity by inhibiting adipose tissue hypertrophy by suppressing adipogenesis.
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Adipogénesis/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Fermentación , Ajo , Lactobacillus plantarum/metabolismo , Obesidad/metabolismo , Extractos Vegetales/farmacología , Tejido Adiposo/metabolismo , Animales , Fármacos Antiobesidad/uso terapéutico , Peso Corporal/efectos de los fármacos , Proteína alfa Potenciadora de Unión a CCAAT/sangre , Colesterol/sangre , Dieta Alta en Grasa , Regulación hacia Abajo , Metabolismo de los Lípidos/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/tratamiento farmacológico , PPAR gamma/sangre , Fitoterapia , Extractos Vegetales/uso terapéutico , ARN Mensajero/metabolismo , Estearoil-CoA Desaturasa/sangre , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/sangre , Triglicéridos/sangreRESUMEN
BACKGROUND: Sleep deprivation has been associated with obesity among adults, and accumulating data suggests that stearoyl-CoA desaturase 1 (SCD1) expression has a relevant impact on fatty acid (FA) composition of lipid pools and obesity. The aim of this study was to investigate the effect of one-night total sleep deprivation (TSD) on DNA methylation in the 5'-prime region of SCD1, and whether detected changes in DNA methylation are associated with SCD activity indices (product to precursor FA ratios; 16:1n-7/16:0 and 18:1n-9/18:0) derived from serum phospholipids (PL). METHODS: Sixteen young, normal-weight, healthy men completed two study sessions, one with one-night TSD and one with one-night normal sleep (NS). Sleep quality and length was assessed by polysomnography, and consisted of electroencephalography, electrooculography, and electromyography. Fasting whole blood samples were collected on the subsequent morning for analysis of DNA methylation and FAs in serum PL. Linear regression analyses were performed to assess the association between changes in DNA methylation and SCD activity indices. RESULTS: Three CpG sites close to the transcription start site (TSS) of SCD1 (cg00954566, cg24503796, cg14089512) were significantly differentially methylated in dependency of sleep duration (-log10 P-value > 1.3). Both SCD-16 and SCD-18 activity indices were significantly elevated (P < 0.05) following one-night TSD, and significantly associated with DNA methylation changes of the three mentioned probes in the 5' region of SCD1. CONCLUSION: Our results suggest a relevant link between TSD, hepatic SCD1 expression and de-novo fatty acid synthesis via epigenetically driven regulatory mechanisms.
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Metilación de ADN , Regulación Enzimológica de la Expresión Génica , Privación de Sueño/enzimología , Estearoil-CoA Desaturasa/genética , Adulto , Estudios Cruzados , Hepatocitos/enzimología , Humanos , Masculino , Privación de Sueño/sangre , Privación de Sueño/genética , Estearoil-CoA Desaturasa/sangre , Adulto JovenRESUMEN
PURPOSE: To examine the longitudinal associations of serum fatty acid composition with type 2 diabetes, insulin secretion and insulin sensitivity over several years. METHODS: We conducted a prospective cohort study derived from the randomized Finnish Diabetes Prevention Study. Total serum fatty acid composition was measured using gas chromatography in 407 overweight, middle-aged people with impaired glucose tolerance at baseline (1993-1998) and annually during the intervention period (1994-2000). Longitudinal associations of 20 fatty acids and three desaturase activities (Δ5 (20:4n-6/20:3n-6, D5D), Δ6 (18:3n-6/18:2n-6, D6D), stearoyl-CoA desaturase-1 (16:1n-7/16:0, SCD-1)) with type 2 diabetes incidence, and estimates of insulin sensitivity (Matsuda), secretion (ratio of insulin and glucose concentrations) and ß-cell function (disposition index) by an oral glucose tolerance test were analyzed using Cox regression and linear mixed models. We validated estimated D5D and D6D using a known FADS1 gene variant, rs174550. RESULTS: The baseline proportions of 20:5n-3, 22:5n-3 and 22:6n-3, and D5D were associated with lower incidence of type 2 diabetes during a median follow-up of 11 years (HR per 1SD: 0.72, 0.74, 0.73, 0.78, respectively, P ≤ 0.01). These long-chain omega-3 fatty acids and D5D were associated with higher insulin sensitivity in subsequent years but not with disposition index. Saturated, monounsaturated and trans fatty acids and 18:3n-3, 18:2n-6, SCD-1 and D6D were inconsistently associated with type 2 diabetes or related traits. CONCLUSIONS: Serum long-chain omega-3 fatty acids and D5D predicted lower type 2 diabetes incidence in people at a high risk of diabetes attending to an intervention study; a putative mechanism behind these associations was higher insulin sensitivity.
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Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Ácidos Grasos/sangre , Insulina/metabolismo , Adulto , Anciano , Índice de Masa Corporal , delta-5 Desaturasa de Ácido Graso , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/análisis , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/análisis , Fibras de la Dieta/administración & dosificación , Fibras de la Dieta/análisis , Ingestión de Energía , Ejercicio Físico , Ácido Graso Desaturasas/sangre , Ácido Graso Desaturasas/genética , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/sangre , Femenino , Finlandia , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina , Secreción de Insulina , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sobrepeso/sangre , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Estearoil-CoA Desaturasa/sangreRESUMEN
BACKGROUND: An association between desaturase activity and risk of type 2 diabetes (T2D) has been found in epidemiologic studies, but little is known about potential mediators of this association. OBJECTIVE: We aimed to investigate the potential role of diabetes-related biomarkers as mediators of the association between estimated Δ5 desaturase (D5D), Δ6 desaturase (D6D), and stearoyl-CoA desaturase (SCD) activity and T2D risk. DESIGN: We analyzed a case-cohort study (subcohort: n = 1533; verified incident T2D cases: n = 400), nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam Study involving 27,548 middle-aged participants. We evaluated the impact of adjustment for several T2D-related biomarkers reflecting liver fat accumulation [reflected by γ-glutamyltransferase (GGT), alanine transaminase (ALT), fetuin-A, and the algorithm-based fatty liver index (FLI)], dyslipidemia (high-density lipoprotein cholesterol, triglycerides), inflammation [C-reactive protein (CRP)], and adiponectin on the association between D5D, D6D, and SCD activity, estimated with fatty acid product-to-precursor ratios derived from erythrocyte membrane proportions, and T2D risk. RESULTS: Estimated D5D activity was inversely associated with T2D risk, whereas D6D and SCD activities were positively associated with risk of T2D [HRs (95% CIs) (highest vs. lowest tertile): 0.51 (0.36, 0.73), 1.68 (1.18, 2.39), and 1.82 (1.29, 2.58), respectively]. The association between estimated D5D, D6D, and SCD activities and risk of T2D was statistically significantly and markedly attenuated after adjustment for the FLI and, to a lesser extent, after adjustment for triglycerides, whereas adjustment for other desaturase-associated biomarkers (CRP, fetuin-A, ALT, and GGT) did not lead to appreciable attenuations. CONCLUSIONS: Liver fat accumulation, as reflected by the FLI, and dyslipidemia, as reflected by triglycerides, may partly explain the association between estimated D5D, D6D, and SCD activity and T2D risk.
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Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Ácido Graso Desaturasas/sangre , Linoleoil-CoA Desaturasa/sangre , Estearoil-CoA Desaturasa/sangre , Adiponectina/sangre , Adulto , Alanina Transaminasa/sangre , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , HDL-Colesterol/sangre , Estudios Transversales , delta-5 Desaturasa de Ácido Graso , Europa (Continente)/epidemiología , Hígado Graso/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Encuestas y Cuestionarios , Triglicéridos/sangre , Circunferencia de la Cintura , Población Blanca , alfa-2-Glicoproteína-HS/metabolismo , gamma-Glutamiltransferasa/sangreRESUMEN
BACKGROUND: High carbohydrate feeding is known to increase plasma triglycerides as well as hepatic de novo lipogenesis (DNL) and may be implicated in the development of hepatic insulin resistance and fatty liver. Unfortunately, it is technically challenging to determine what proportion of circulating plasma triglycerides have been derived from the newly synthesized fatty acids in the postprandial period. The aims of this study were to 1) characterize the changes in the plasma postprandial total fatty acid pool in beagles following the consumption of meals containing 44% (Control) and 74% (High Sucrose) carbohydrate and 2) determine if changes in plasma fatty acid concentration and delta-9 desaturation index (DI) would be useful as simple and easy to measure biomarkers of systemic DNL. FINDINGS: No differences in plasma total palmitic acid (16:0), stearic acid (18:0) and oleic acid (18:1) concentrations or delta-9 DI for the total 18:0 and 18:1 pools between High Sucrose and Controls were observed. However, newly synthesized 16:0 (2.6 ± 0.2% vs. 8.8 ± 2.0%; p = 0.016), 18:0 (0.93 ± 0.2% vs. 4.1 ± 1.7%; p = 0.007) and 18:1 (0.29 ± 0.09% vs. 3.5 ± 1.2%; p = 0.017) were higher in High Sucrose versus Control animals, respectively. Also, the delta-9 DI for the newly synthesized 18:0 and 18:1 pools was higher at 2 and 6 hours postprandial, with a pattern of change which supports the increased stearoyl-CoA desaturase (SCD-1) activity following high carbohydrate feeding followed by a down regulation of this enzyme. CONCLUSIONS: Our data show that high sucrose meals increase the relative contribution of systemic DNL produced fatty acids to the total postprandial plasma fatty acid pool. These data also show that a different pattern of both fatty acid synthesis and disposal occurs depending on energy and macronutrient profile of the meal. These changes are in spite of no observable changes in the plasma concentrations or ratios of the total fatty acid pool opposed to the observed changes in the newly synthesized fatty acid pool.