RS2289487 variation in PERILIPIN gene is a predictor of weight loss and protection against impaired glucose metabolism after a meal-replacement diet in postmenopausal obese females.

OBJECTIVE: The PERILIPIN1 (PLIN1) gene encodes an adipocyte-associated protein that modulates weight. The objective was to evaluate the role of the rs2289487 genetic variant of the PLIN1 gene on weight loss and glucose metabolism secondary to a partial meal replacement (pMR) hypocaloric diet. PATIENTS AND METHODS: We conducted an interventional study in 111 postmenopausal obese females with body mass index (BMI) > 35 kg/m2. The subjects received two intakes per day of a normocaloric hyperproteic formula for 12 weeks. RESULTS: After the pMR diet, body weight, (BMI), fat mass, waist circumference, fasting insulin levels and HOMA-IR decreased in both genotype groups. The improvements in these parameters were higher in C allele carriers than in subjects with TT genotype. The percentage of patients who achieved 7.5% weight loss was higher in the C carriers (57.4% vs. 27.6%), (adjusted Odds Ratio 2.14, 95% CI = 1.33-9.40; p = 0.02). The decrease in the percentage of diabetes mellitus or impaired fasting glucose decrease was statistically significant in C allele carriers (30.2% vs. 18.9%; p = 0.01) (OR 0.54, 95% CI = 0.22-0.78; p = 0.02). CONCLUSIONS: The C allele of rs2289487 predicts the magnitude of weight loss resulting from a pMR diet. These adiposity improvements produce a better improvement in insulin resistance and the percentage of impaired glucose metabolism.

Relation of a variant in adiponectin gene (rs266729) with metabolic syndrome and diabetes mellitus type 2 in adult obese subjects.

OBJECTIVE: Some studies in the literature indicate that ADIPOQ rs266729 polymorphism functionally regulates adiponectin promoter activity and secondarily adiponectin levels. The aim of the present investigation was to describe the association of rs266729 with diabetes mellitus (DM2), components of Metabolic syndrome (MS) and serum adiponectin levels. PATIENTS AND METHODS: The study involved a population of 1004 adult obese subjects. Measurements of anthropometric parameters, blood pressure, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile, adipokines levels and prevalence of MS and DM2 were recorded. The genotype of ADIPOQ gene polymorphism (rs266729) was evaluated. RESULTS: The distribution of the rs266729 polymorphism in this population was 56.7% (n=569) (CC), 33.1% (n=332) (CG) and 10.2% (n=103) (GG). Insulin and HOMA-IR levels were higher in G allele carriers than non G allele carriers. Adiponectin levels were lower in G allele carriers than non G allele carriers. In total group carriers of G allele, logistic regression analysis showed an increased risk of hyperglycaemia (OR=1.70, 95% CI=1.19-2.76, p=0.03) and prevalence of diabetes mellitus type 2 (OR=1.81, 95% CI=1.13-5.14, p=0.04), after adjusting by body mass index and age CONCLUSIONS: G allele of SNP (rs266729) of the ADIPOQ gene showed high values of insulin and HOMA-IR, and low values of adiponectin levels than non G allele carriers. G allele carriers showed higher rate of diabetes mellitus and hyperglycemia.

Effect of two different dietary fatty acid profiles and variant rs266729 in ADIPOQ on weight loss and adiponectin concentrations / Efecto de dos perfiles diferentes de ácidos grasos en la dieta y variante en el gen rs266729 de adiponectina sobre la pérdida de peso y los niveles de adiponectina

BACKGROUND: The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE: To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN: A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS: Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG ± GG) -9.0 ±1.1 mU/L vs. -4.5 ± 2.4 mg/dL, p = 0.01), LDL cholesterol (-6.0 ± 1.1 mg/dL vs. -3.0 ± 0.9 mg/dL, p = 0.03), glucose (-4.7 ± 1.1 mg/dL vs. -0.6 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.6 ±1.0 mU/L vs. -0.7 ± 0.3 mU/L, p = 0.02) and in HOMA-IR (-0.5 ± 0.2 units vs. -0.2 ± 0.4 units, p = 0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0 ± 1.2mU/L vs. -2.1 ± 1.4 mg/dL, p = 0.02), LDL cholesterol (-7.3 ± 1.2 mg/dL vs. -2.1 ± 0.8 mg/dL, p = 0.02), glucose (-3.2 ± 0.1mg/dL vs. -0.2 ± 0.5 mg/dL, p = 0.01), and insulin levels (-2.5 ± 1.0 mU/L vs. -1 ± 0.6 mU/L, p = 0.02) and HOMA-IR (-0.5 ± 0.1 units vs. −0.3 ± 0.4 units, p = 0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3 ± 2.0 ng/dL vs. Diet P: 9.3 ± 2.9 ng/dL, p = 0.43). CONCLUSION: The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss

ANTECEDENTES: El papel de las variantes del gen ADIPOQ en la pérdida de peso después de una intervención dietética sigue sin estar claro. OBJETIVO: Nuestro objetivo fue analizar los efectos de la variante rs266729 del gen ADIPOQ sobre la pérdida de peso, los factores de riesgo cardiovascular y los niveles de adiponectina después de 2 dietas hipocalóricas con diferentes perfiles de grasas en la dieta. DISEÑO: Una población de 362 pacientes obesos se incluyeron en un ensayo clínico aleatorizado con 2 dietas (dieta M: dieta enriquecida con grasas monoinsaturadas y dieta P: dieta enriquecida con grasas poliinsaturadas). Antes y tras 12 semanas, se realizó una evaluación antropométrica, evaluación de la ingesta nutricional y un análisis bioquímico. RESULTADOS: La pérdida de peso fue similar con ambas dietas. Después de la dieta M, solo los sujetos con genotipo CC mostraron una mejoría significativa en el colesterol total (CC vs. CG±GG) (-9,0 ± 1,1 mU/l vs. - 4,5 ± 2,4 mg/dl; p = 0,01), colesterol LDL (-6,0 ± 1,1 mg/dl vs. - 3,0 ± 0,9 mg/dl; p = 0,03), glucosa (-4,7 ± 1,1 mg/dl vs. -0,6 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,6 ± 1,0 mU/l vs. -0,7± 0,3 mU/l; p = 0,02) y HOMA-IR (- 0,5 ± 0,2 unidades vs. -0,2 ± 0,4 unidades; p = 0,03). La misma mejora en todos los parámetros se informó después de la dieta P; niveles de colesterol total (CC vs. CG ± GG) (-8,0 ± 1,2 mU/l vs. -2,1 ± 1,4 mg/dl; p = 0,02), colesterol LDL (-7,3 ± 1,2 mg/dl vs. -2,1 ±0,8 mg/dl; p = 0,02), glucosa (-3,2 ± 0,1 mg/dl vs. -0,2 ± 0,5 mg/dl; p = 0,01), niveles de insulina (-2,5 ±1,0 mU/l vs. -1 ±0,6 mU/l; p = 0,02) y HOMA-IR (-0,5 ± 0,1 unidades vs. -0,3 ± 0,4 unidades; p = 0,02). Solo los sujetos con genotipo CC mostraron un aumento significativo de los niveles de adiponectina después de ambas dietas: (dieta M: 10,3 ± 2,0 ng/dl vs. dieta P: 9,3 ± 2,9 ng/dl; p = 0,43). CONCLUSIÓN: El genotipo CC de la variante rs266729 del gen ADIPOQ se asocia con aumentos en los niveles de adiponectina y disminución del colesterol LDL, glucosa, insulina y HOMA-IR tras la pérdida de peso

RS9939609 FTO gene variant modified weight loss and insulin resistance after a partial meal-replacement hypocaloric diet.

OBJECTIVE: Some studies have demonstrated that the allele A of FTO rs9939609 is related to both higher waist circumference and body mass index. Subsequently, some designs related biochemical variables and body weight changes with this genetic variant. We decide to analyze the effects of rs9939609 genetic variant of FTO gene on metabolic parameters and weight loss secondary to partial meal replacements hypocaloric diets (pMRHDs) in obese subjects. PATIENTS AND METHODS: This was a non-randomized, single-treatment study with a formula-diet in 44 obese subjects. The patients received nutritional education and a pMRHDs with two intakes of normocaloric hyperproteic formula during 12 weeks. Anthropometric parameters and biochemical profiles were measured at basal time and after 12 weeks. The variant of FTO gene rs9939609 was determined. RESULTS: Genotype distribution (n=44) was (16 TT (36.4%), 17 TA (38.6%) and 11 AA (25.0%)). After the pMRHD, body weight, body mass index (BMI), fat mass, waist circumference, serum leptin levels and systolic blood pressure improved in both genotypes without statistical differences in both branches. After dietary intervention with pMRHD, subjects with A allele showed a significant improvement in total cholesterol levels (TT vs. TA+AA) (-3.8±1.4 md/dL vs. -12.6±1.7 mg/dl: p=0.01), LDL-cholesterol (-0.2±1.5 md/dL vs. -10.5±1.9 mg/dl: p=0.02), insulin levels (-1.9±0.2 mU/L vs. -3.8±0.3 mU/L: p=0.02) and HOMA-IR (-0.6±0.2 units vs. -1.1±0.1 units: p=0.01). CONCLUSIONS: Our data suggest that the genetic variant (rs9939609) of FTO gene showed better improvement of LDL-cholesterol, insulin and HOMA-IR in subjects with A allele.

Uso de treprostinil sistémico en una paciente con hipertensión pulmonar grave, sin respuesta a la máxima terapia disponible / Use of treprostinil in a patient with a severe pulmonary arterial hypertension no responding to the maximal therapy available

En los pacientes con Hipertensión Arterial Pulmonar (HAP) de alto riesgo, en clase funcional (CF)IV, la terapia específica debe ser combinada y debe incluir una prostaciclina (PGI2) de uso sistémico en espera de trasplante bipulmonar (TBP). En el sistema público la única PGI2 disponible para asociar a Sildenafil y algún inhibidor de endotelina (Ambrisentan o Bosentan) es Iloprost nebulizado, que si bien es efectiva, no logra estabilizar los casos graves con severa disfunción del ventrículo derecho (VD). Se presenta el primer caso en el Instituto del Tórax, centro de referencia nacional de HAP, del uso de treprostinil en una paciente de 24 años con HAP grave e indicación de TBP. Treprostinil es un análogo sintético de PGI2 de uso subcutáneo en dosis desde 1 a 40 ng/kg/min. La paciente presentaba una situación de extrema gravedad: CF IV, distancia recorrida en el test de caminata de 6 min (DRTC 6 min) < 300 m,derrame pericárdico y severa disfunción del VD con TAPSE (índice de disfunción del VD) de 13 cm/s asociado a ProBNP >2.500 pg/ml. Luego de 6 meses de hospitalización en intermedio, terapia triple (Sildenafil, Ambrisentan e Iloprost nebulizado) asociado a O2,diuréticos y milrinona, logró ser dada de alta a las 3 semanas del inicio de treprostinil, regresando al trabajo a los 2 meses y estabilizando su condición en CF III, con DRTC 6 min > 440 m, mejoría de la función del VD(TAPSE 19). El ProBNP persistió elevado, 1.491 pg/ml, indicando que su enfermedad es grave y progresiva; sin embargo, ha logrado un nivel de estabilidad clínica que le permite una adecuada vida de relación familiar y laboral.

In high risk Pulmonary Arterial Hypertension (PAH) patients with functional class (FC) IV, specific therapy must be combined and must include systemic prostacyclin (PGI2), meanwhile they are enlisted for double lung transplant (DLT). In Chilean Public Health System, nebulized Iloprost is the only PGI2 available to combine with Sildenafil and either Ambrisentan or Bosentan as endothelin receptor antagonist. This association is not enough for severe cases with right ventricular (RV) dysfunction. The first case from the National Institute of Thorax as a referral center is presented now in a 24 years-old lady treated with treprostinil. She has severe PAH with DLT indication. Treprostinil is a PGI2 analog, for subcutaneous use in a dose from 1 to 40 ng/kg/min. She was extremely sick, with FC IV, she walked < 300 m at 6 min walking test (6 MWT), presented pericardial effusion and severe RV dysfunction, with TAPSE (echocardiography index for RV dysfunction)=13 cm/s, ProBNP > 2,500 pg/ml. Six months after being at intensive care unit with triple therapy (Sildenafil, ambrisentan and nebulized Iloprost) plus oxygen, diuretics and milrinone, she was finally discharged after receiving a 3 weeks treprostinil course. She came back to work two months later and her condition was more stable: FC III, she walked > 440 m at 6MWT, with a significant improvement in RV function with TAPSE = 19. Although ProBNP decreased to 1,491pg/ml, it was still high, pointing out the progressive nature of her disease. However, she met a better clinical condition which allows her to reach a much better quality of life from a personal, familial and social point of view.

Effect of two different dietary fatty acid profiles and variant rs266729 in ADIPOQ on weight loss and adiponectin concentrations.

BACKGROUND: The role of ADIPOQ gene rs266729 variants on weight loss after a dietary intervention are still unclear. OBJECTIVE: To analyze the effects of the ADIPOQ gene rs266729 variant n weight loss, cardiovascular risk factors, and adiponectin levels after two hypocaloric diets with different dietary fatty profiles. DESIGN: A population of 362 obese patients was enrolled in a randomized clinical trial with two diets (Diet M, monounsaturated fat-enriched diet, and Diet P, polyunsaturated-fat enriched diet). Anthropometric measurements, an assessment of nutritional intake, and biochemical tests were performed at baseline and after 12 weeks. RESULTS: Weight loss was similar with both diets. After Diet M, only subjects with CC genotype showed significant improvements in total cholesterol (CC vs. CG±GG) (-9.0±1.1mU/L vs. -4.5±2.4mg/dL, p=0.01), LDL cholesterol (-6.0±1.1mg/dL vs. -3.0±0.9mg/dL, p=0.03), glucose (-4.7±1.1mg/dL vs. -0.6±0.5mg/dL, p=0.01), and insulin levels (-2.6±1.0mU/L vs. -0.7±0.3mU/L, p=0.02) and in HOMA-IR (-0.5±0.2 units vs. -0.2±0.4 units, p=0.03). The same improvement was reported after Diet P in all parameters, including total cholesterol (CC vs. CG±GG) (-8.0±1.2mU/L vs. -2.1±1.4mg/dL, p=0.02), LDL cholesterol (-7.3±1.2mg/dL vs. -2.1±0.8mg/dL, p=0.02), glucose (-3.2±0.1mg/dL vs. -0.2±0.5mg/dL, p=0.01), and insulin levels (-2.5±1.0mU/L vs. -1±0.6mU/L, p=0.02) and HOMA-IR (-0.5±0.1 units vs. -0.3±0.4 units, p=0.02). Only subjects with CC genotype showed significant increases in adiponectin levels after both diets: (Diet M: 10.3±2.0ng/dL vs. Diet P: 9.3±2.9ng/dL, p=0.43). CONCLUSION: The CC genotype of ADIPOQ gene rs266729 variant is associated to increased adiponectin levels and decreases in LDL cholesterol, glucose, insulin, and HOMA-IR levels after weight loss.

Single nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 interact with different type of dietary fatty acids in two hypocaloric diets.

OBJECTIVE: Some adiponectin gene (ADIPOQ) and single nucleotide polymorphisms (SNPs) have been related to adiponectin levels and metabolic parameters. Few studies of interaction gene-nutrient have been realized in this topic area. The aim of our study was to analyze the effect of the rs1501299 ADIPOQ gene polymorphism, and the dietary intake on total adiponectin levels and the insulin resistance changes after an enriched-monounsaturated fat (Diet M) vs. an enriched-polyunsaturated fat hypocaloric diet (Diet P). PATIENTS AND METHODS: A Caucasian population of 363 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets. Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild). RESULTS: With both caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure and leptin levels decreased. After Diet P, only subjects with GG genotype showed a significant improvement in the insulin levels (GG vs. GT±TT) (-3.2±1.0 mU/L vs. -0.6±0.4 mU/L: p=0.01) and in the homeostasis model assessment (HOMA-IR) (-1.1±0.2 units vs. -0.3±0.4 units: p=0.02). The same improvement in both parameters was reported after Diet M: insulin levels (-3.7±0.9 mU/L vs. -0.4±0.5 mU/L: p=0.01) and HOMA-IR (-1.0±0.2 units vs. -0.4±0.3 units: p=0.03). After weight loss with diet M, both genotypes (GG vs. GT±TT) showed similar decrease in total cholesterol and LDL-cholesterol. Only subjects with GG genotype showed a significant increase of the adiponectin levels after both diets: (Diet P: 9.3±3.0 ng/dl vs. Diet M: 8.2±2.9 ng/dl: p=0.38). CONCLUSIONS: The GG genotype of ADIPOQ gene variant (rs1501299) is associated to a significant improvement in the adiponectin levels and a decrease of insulin and HOMA-IR after two different hypocaloric diets with different profile of unsaturated dietary fats.

Role of rs670 variant of APOA1 gene on metabolic response after a high fat vs. a low fat hypocaloric diets in obese human subjects.

BACKGROUND & AIMS: A common G-to-A transition located 75 base pairs upstream (rs670) from transcription start site of the APOA1 gene has been related with some metabolic parameters. Our aim was to analyze the effects of rs670 APOA1 gene polymorphism on lipid profile and metabolic changes after two different hypocaloric diets. METHODS: 282 obese subjects were randomly allocated during 12 weeks (Diet HF - high fat diet vs. Diet LF - low fat diet). Anthropometric and biochemical status were evaluated. RESULTS: Body mass index, weight, fat mass, waist circumference, systolic blood pressure, leptin levels and waist circumference decreased in all patients in average after both diets. In A allele carriers after 12 weeks with both diets, insulin levels (Delta diet HF: -5.3 + 1.2 UI/L; P = 0.02 and Delta diet LF: -5.8 + 1.3 UI/L; P = 0.02) and HOMA-IR (Delta diet HF: -2.9 + 0.8 units; P = 0.01 and Delta diet LF: -2.2 + 0.9 units; P = 0.03) improved in a significant way. With the low fat diet, A allele carriers showed a statistical improvement in HDL-cholesterol levels (Delta: 4 + 1 mg/dl; P = 0.03). CONCLUSIONS: Our study showed the association of rs670 ApoA1 polymorphism with a decrease of insulin resistance induced by both diets and provided additional evidence on HDL-cholesterol increase after a LF hypocaloric diet in A allele carriers.

Common polymorphism in the cannabinoid receptor gene type 2 (CB2R) rs3123554 are associated with metabolic changes after two different hypocaloric diets with different dietary fatty profiles.

BACKGROUND: The role of CB2R gene variants on weight loss after a dietary intervention has been investigated in few studies. OBJECTIVE: We evaluate the effect of this genetic variant (rs3123554) of CB2R gene on cardiovascular risk factors and weight loss secondary to high monounsaturated fat vs a high polyunsaturated fat hypocaloric diets. DESIGN: A Caucasian population of 362 obese patients was enrolled. Patients were randomly allocated during 3 months to one of two diets (Diet P high polyunsaturated (PUFAs) fat hypocaloric diet vs, Diet M high monounsaturated (MUFAs) fat hypocaloric diet). RESULTS: In both genotype groups (GG vs GA+AA), body weight, body mass index (BMI), fat mass, waist circumference and systolic blood pressure decreased after diet P and M. Body weight, BMI, fat mass and waist circumference were higher in A allele carriers than non A allele carriers. The improvement of these parameters was higher in non A allele carriers than A allele carriers. In non A allele carriers with both diets, the decrease of total cholesterol, LDL-cholesterol, insulin and HOMA-IR was higher than A allele carriers after both diets. After diet P, triglyceride levels decrease in non A allele carriers. CONCLUSION: Our data suggest that carriers of the minor allele of rs3123554 variant of CB2R gene lose less body weight during to different hypocaloric diets with different fatty acid. Moreover, non A-allele carriers showed a better response of LDL-cholesterol, HOMA-IR and insulin levels than A-carriers with both hypocaloric diets.

The association of the rs670 variant of APOA1 gene with insulin resistance and lipid profile in morbid obese patients after a biliopancreatic diversion surgery.

OBJECTIVE: A common G-to-A transition (rs670) of the Apoprotein subtype 1 APOA1 gene has been evaluated. The presence of the A allele has been related with increased activity. We investigated the role of this genetic variant (rs670) on lipoprotein levels and anthropometric parameters after biliopancreatic diversion (BPD) surgery in morbid obese patients. PATIENTS AND METHODS: Sixty-three patients with morbid obesity without diabetes mellitus type 2 were enrolled. Biochemical and anthropometric evaluation were registered before and after one, two and three years follow-up. RESULTS: Genotype distribution was 73% (n=46) GG, 25.6% (n=16) GA and 1.4% (n=1) AA for the rs670 polymorphism. Percent excess weight loss, anthropometric and biochemical parameters improved in both groups (GG vs. GA±AA). The decrease of fasting insulin levels at 1 years (delta: -3.7±1.4 mUI/L vs. -2.9±1.2 mUI/L; p=0.02), 2 years (delta: -4.8±0.3 mUI/L vs. -4.0±0.2 mUI/L; p=0.01) and 3 years (delta: -6.7±3.1 mUI/L vs. -3.9±2.1 mUI/L; p=0.03) was higher in A allele carriers than in non carriers. The improvement of HOMA-IR levels at 1 years (delta: -3.7±1.4 mUI/L vs. -2.9±1.2 mUI/L; p=0.02), 2 years (delta: -4.8±0.3 mUI/L vs. -4.0±0.2 mUI/L; p=0.01) and 3 years (delta: -6.7±3.1 mUI/L vs. -3.9±2.1 mUI/L; p=0.03) was also higher in A allele carriers than non-carriers. Finally, the increase of HDL-cholesterol levels at 1 years (delta: 2.2±0.6 mg/dl vs. -1.2±0.2 mg/dl; p=0.001), 2 years (delta: 2.5±0.4 mg/dl vs. 0.3±0.1 mg/dl; p=0.01) and 3 years (delta: 2.4±0.6 mg/dl vs. 0.4±2.3 mg/dl; p=0.02) was higher in A allele carriers than non-carriers. CONCLUSIONS: This variant of the APOA1 gene showed important effects on HDL-cholesterol, HOMA-IR and insulin resistance after DBP for 3 years.

Effect of the rs1862513 variant of resistin gene on insulin resistance and resistin levels after two hypocaloric diets with different fat distribution in subjects with obesity.

OBJECTIVE: Polymorphisms of a single nucleotide in resistin gene (RETN) have been associated with insulin resistance. We decide to investigate the role of this polymorphism on insulin resistance and resistin levels after two hypocaloric diets. PATIENTS AND METHODS: A sample of 361 obese non-diabetic Caucasian was enrolled. Biochemical evaluation and anthropometric data were measured at the start of the trial and repeated after 3 months of both diets (Diet P, Polyunsaturated vs. diet M, Monounsaturated). RESULTS: With both diets and in both genotype groups, BMI, weight, fat mass, waist circumference, systolic blood pressure, and diastolic blood pressure decreased. After diet P, insulin levels (GG vs. GC+CC genotypes) (-1.2±3.8 UI/L vs. -0.7±2.1 UI/L; p<0.05), HOMA-IR (-0.6±1.0 units vs. -0.4±0.9 units; p<0.05), total cholesterol (-10.5±20.1 mg/dl vs. -6.1±15.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.6±10.1 mg/dl vs. -2.2±9.1 mg/dl; p<0.05) decreased in subjects with GG genotype. After diet M, insulin levels (-1.8±2.1 UI/L vs. -0.6±3.0 UI/L: p>0.05), HOMA-IR (-0.5±1.0 units vs. -0.3±1.1 units: p>0.05), total cholesterol (-9.5±13.1 mg/dl vs. -4.4±8.1 mg/dl; p<0.05) and LDL-total cholesterol (-8.1±6.1 mg/dl vs. -2.9±9.1 mg/dl; p<0.05) decreased, too. CONCLUSIONS: We suggest that GG genotype of RETN rs1862513 could be a predictor of the reduction of HOMA-IR, insulin, and LDL cholesterol secondary to two hypocaloric diet in obese subjects.

Role of rs670 variant of APOA1 gene on lipid profile, insulin resistance and adipokine levels in obese subjects after weight loss with a dietary intervention.

OBJECTIVE: The aim of this study was to analyze the effects of rs670 APOA1 gene polymorphism on obesity parameters, lipid profile, glucose metabolism markers, blood pressure and adipokine levels after a hypocaloric diet with Mediterranean pattern. MATERIAL AND METHODS: A population of 82 obese patients was studied before and after 12 weeks on a hypocaloric diet (500 kcal per day) in an interventional study of one arm. GG and GA + AA subjects receiving the same diet. Anthropometric measures and biochemical parameters (lipid profile, glucose metabolism, blood pressure and adipokine levels) were measured. Genotype of ApoA1 gene polymorphism (rs670) was evaluated. The A allele is the risk allele. RESULTS: After dietary intervention and in both genotype groups (GG vs. GA + AA), body mass index (BMI) (delta: -1.0 ±â€¯0.8 kg/m2 vs. -1.4 ±â€¯1.0 kg/m2: p = 0.02), weight (delta: -2.6 ±â€¯2.1 kg vs. -3.6 ±â€¯2.2 kg: p = 0.03), fat mass (delta: -1.6 ±â€¯1.1 kg vs. -3.2 ±â€¯1.0 kg: p = 0.01) and waist circumference (delta: -1.8 ±â€¯0.6 cm vs. -2.2 ±â€¯1.1 cm: p = 0.02) decreased. The decrease of the anthropometric parameters was higher in A allele carriers than non-A allele carriers. In A allele carriers, total cholesterol (delta: -11.1 ±â€¯7.1 mg/dl vs. -20.1 ±â€¯9.0 mg/dl: p = 0.02), LDL cholesterol (delta: -10.7 ±â€¯4.1 mg/dl vs. -21.2 ±â€¯8.0 mg/dl: p = 0.01), insulin levels (delta: -0.6 ±â€¯0.8 UI/L vs. 3.7 ±â€¯1.1 UI/L; p = 0.002) and insulin resistance with HOMA-IR (delta: -0.2 ±â€¯0.3 units vs. 0.8 ±â€¯0.4 units; p = 0.01) decreased. The improvement of leptin was similar in both genotype groups. Resistin and adiponectin levels remained unchanged after dietary intervention. CONCLUSION: In this study the APOA1 (rs670) gene showed important effects on body weight, adiposity, LDL-cholesterol levels and insulin resistance after 12 weeks of the dietary intervention.

Effects of polymorphism rs3123554 in the cannabinoid receptor gene type 2 (CB2R) on metabolic and adiposity parameters after weight loss with two hypocaloric diets.

BACKGROUND: The role of CB2R gene variants on weight loss after a dietary intervention remained unclear. OBJECTIVE: Our aim was to analyze the effects of rs3123554 of CB2R receptor gene on metabolic and adiposity parameters after two different hypocaloric diets in obese subjects. DESIGN: A Caucasian population of 280 obese patients was enrolled. Patients were randomly allocated during 3 months to one of two diets (Diet I - moderate in carbohydrate. Vs Diet II - normal in carbohydrate). RESULTS: In both genotype groups (GG vs GA + AA), body weight, body mass index (BMI), fat mass, waist circumference and systolic blood pressure decreased after diet I and II. The decrease of these parameters was higher in non A allele carriers than A allele carriers. Pre- and post-dietary intervention, body weight, BMI, fat mass and waist circumference were higher in A allele carriers than non A allele carriers. In non A allele carriers, the decrease of glucose, insulin, HOMA-IR and Interleukin-6 levels was higher than A allele carriers after both diets. CONCLUSION: Carriers of the minor allele of rs3123554 variant of CB2R gene loose less body weight during two different hypocaloric diets. The improvement of metabolic parameters was better in no A allele carriers than A allele carriers.

The association of SNP276G>T at adiponectin gene with insulin resistance and circulating adiponectin in response to two different hypocaloric diets.

BACKGROUND: Several adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPS) have been related with adiponectin levels and risk for obesity. OBJECTIVE: The aim of our study was to analyze the effect of rs1501299 ADIPOQ gene polymorphism and dietary intake on total adiponectin levels and insulin resistance after two hypocaloric diets in obese subjects. MATERIAL AND METHODS: A Caucasian population of 284 obese patients was enrolled in a randomized clinical trial with two hypocaloric diets (I: moderate carbohydrates vs II: low fat). Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were realized. The statistical analysis was performed for the combined GT and TT as a group (mutant) and GG as second group (wild) (dominant model). RESULTS: The genotype distribution was 149 GG, 124 GT and 21 TT. With caloric restriction strategies, body weight, body mass index (BMI), fat mass, waist circumference, systolic blood pressure, total LDL cholesterol, LDL cholesterol and leptin levels decreased. Only in subjects with GG genotype, diet I and II decreased fasting insulin levels, HOMA-IR and adiponectin levels. The improvement was similar with both diets; insulin concentrations (Diet I: -4.7 ±â€¯1.4 mUI/L vs. Diet II: -5.9 ±â€¯1.9 mUI/L: p = .76), HOMA-IR (Diet I: -1.4 ±â€¯0.6 units vs. Diet II: -2.0 ±â€¯0.7 units: p = .56) and adiponectin levels (Diet I: -10.2 ±â€¯3.4 ng/dl vs. Diet II: -14.0 ±â€¯2.9 ng/dl: p = .33). CONCLUSION: The GG genotype of ADIPOQ gene variant (rs1501299) is associated with an increase in adiponectin levels and a decrease of insulin and HOMA-IR after weight loss.

Association of the rs10830963 polymorphism in melatonin receptor type 1B (MTNR1B) with metabolic response after weight loss secondary to a hypocaloric diet based in Mediterranean style.

BACKGROUND & AIMS: Some genetic variants within MTNR1B were related with fasting glucose levels or the increased prevalence of diabetes mellitus and obesity. The aims of the present investigation were to determine the influence of rs10830963 MTNR1B variant in relation to body weight loss, insulin resistance and adipokine levels in response to a hypocaloric diet with Mediterranean pattern. METHODS: A Caucasian population of 80 obese patients was studied before and after 12 weeks on a hypocaloric diet. Body weight, fat mass, waist circumference, blood pressure, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipoprotein levels and adipocytokines levels (leptin, adiponectin and resistin) were measured. Genotype of MTNR1B gene single nucleotide polymorphism (rs10830963) was evaluated. RESULTS: In total, 44 patients (55%) had the genotype CC, 27 patients CG (33.8%) and 9 patients GG (11.2%). With the dietary intervention body mass index, weight, fat mass, systolic blood pressure, leptin levels and waist circumference decreased in both groups. There were no significant differences between gender groups on the reported effects in each genotype group. However, the improvement of anthropometric parameters was higher in subjects with CC genotype than (GC + GG) genotype. After dietary intervention and in males with CC genotype, insulin levels (-5.3 ± 4.8 UI/L vs 1.2 ± 4.1 UI/L; p < 0.05) and HOMA-IR (-1.4 ± 2.1 units vs 0.4 ± 2.0 units; p < 0.05) decreased. In the group of females with CC genotype, insulin levels (-3.5 ± 2.1 UI/L vs. -1.4 ± 2.2 UI/L: p < 0.05) and HOMA-IR (-1.4 ± 1.2 units vs. -0.1 ± 1.3 units: p < 0.05) decreased, too. However, these parameters remained unchanged in (GC + GG) group. Fasting glucose levels were higher in patients in (GC + GG). CONCLUSIONS: This study showed the association of rs10830963 MTNR1B single nucleotide polymorphism with body weight loss and changes in fasting insulin levels and HOMA-IR in obese subjects.

Modifications of serum levels of omentin-1 and other cardiovascular risk factors following weight loss secondary to a Mediterranean hypocaloric diet.

BACKGROUND & AIMS: Omentin-1 might play a role on insulin resistance, dyslipidemia and obesity. The aim of this investigation was to evaluate the influence of weight loss on omentin-1 concentrations after a hypocaloric diet with Mediterranean pattern. METHODS: A Caucasian sample of 67 obese patients was analyzed before and after 3 months on a hypocaloric diet. Anthropometric parameters, blood pressure, fasting blood glucose, C-reactive protein (CRP), fasting insulin, insulin resistance (HOMA-IR), lipid concentrations and omentin-1 were measured. RESULTS: Sixty-seven obese subjects were enrolled in the study. The mean age was 48.3 ± 8.0 years (range: 25-66) and the mean BMI 34.5 ± 4.8 kg/m2 (range: 30.2-40.8). Gender distribution was 50 females (74.6%) and 17 males (25.4%). After dietary intervention and in males and females; body mass index, weight, fat mass, waist circumference, blood pressure, glucose, LDL cholesterol, insulin and HOMA-IR decreased. Omentin-1 levels increase after dietary intervention (males vs females) (delta basal vs 3 months: 10.0 ± 3.8 ng/dl: p = 0.01 vs 9.9 ± 4.1 ng/dl; p = 0.03). In the multiple regression analysis adjusted for age and sex; BMI and insulin remained independently associated with baseline and post-treatment levels of omentin-1. CONCLUSIONS: Our investigation showed a significant increase in omentin-1 levels after weight loss secondary to a hypocaloric diet with a Mediterranean pattern.

The Association of SNP276G>T at Adiponectin Gene with Insulin Resistance and Circulating Adiponectin in Morbid Obese Patients After a Biliopancreatic Diversion Surgery.

BACKGROUND: The effects of rs1501299 variant of ADIPO gene on weight loss after bariatric surgery have not been evaluated. We decided to investigate the role of this genetic variant on anthropometric and biochemical outcomes such as serum adiponectin levels after biliopancreatic diversion (BPD) surgery in morbidly obese patients during 3 years. MATERIAL AND METHODS: A sample of 64 patients with morbid obesity without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit during 3 years (1, 2, and 3 years). RESULTS: Percent excess weight loss, body mass index, weight, waist circumference, fat mass, blood pressure, fasting glucose, LDL cholesterol, total cholesterol, and triglycerides levels improved in both genotype groups. Fasting insulin levels and HOMA-IR decreased significantly only in non-T allele carriers. The decrease of fasting insulin levels at 3 years (delta -9.2 ± 3.4 vs -2.9 ± 2.2 mUI/L; p = 0.01) and HOMA-IR (delta -1.3 ± 0.3 vs -0.8 ± 0.4 units; p = 0.03) were higher in non-T allele carriers than T carriers. Adiponectin levels increased in all times after surgery in non-T allele carriers, too. The increase of adiponectin levels at 3 years (delta 12.2 ± 3.6 vs 1.8 ± 1.2 ng/mL; p = 0.01) was higher in non-T allele carriers than T carriers. CONCLUSION: Non-T allele of ADIPOQ gene variant (rs1501299) is associated with increases in adiponectin levels and better improvements of insulin and HOMA-IR after BPD massive weight loss. These parameters remained unchanged in T allele carriers.

Polymorphism of neuropeptide Y gene rs16147 modifies the response to a hypocaloric diet on cardiovascular risk biomarkers and adipokines.

BACKGROUND: The main genetic variant described in NPY gene is rs16147 (G-399A) and it is located within the promoter region upstream of the gene for neropeptide Y (NPY). We evaluate the effects of the rs16147 NPY gene polymorphism on metabolic changes secondary to weight loss after 3 months of a hypocaloric diet in adult obese patients. METHODS: A population of 82 obese patients was analysed in an interventional design of one arm. Before and after 3 months on a hypocaloric diet, an anthropometric evaluation, an assessment of nutritional intake and a biochemical analysis were performed. The statistical analysis was performed for combined GA and AA as a group (minor allele group) and GG as second group (major allele group) (dominant model). RESULTS: In A allele carriers, the mean (SD) decrease in weight was -2.8 (2.2) kg [decrease in non A allele carriers -2.6 (1.1) kg, P > 0.05), body mass index was -1.2 (0.6) kg m-2 [decrease in non A allele carriers -1.1 (0.8) kg m-2 , P > 0.05], fat mass was -1.7 (1.4) kg [decrease in non A allele carriers -1.9 (1.3) kg, P > 0.05], waist circumference was -5.5 (3.4) cm [decrease in non A allele carriers -3.7 (4.1) cm, P = 0.006], C-reactive protein (CRP) was -0.7 (0.6) mg dL-1 [decrease in non A allele carriers -0.1 (0.3) mg dL-1 , P = 0.02], insulin was -1.5 (0.4) mUI L-1 [decrease in non A allele carriers -0.8 (2.0) mUI L-1 , P = 0.001] and homeostasis model assessment-insulin resistance (HOMA-IR) was -0.4 (0.5) [decrease in non A allele carriers -0.2 (0.1), P = 0.005]. interleukin (IL)-6 changes were significant in A allele carriers [-0.7 (0.2) pg mL-1 ] versus non A allele carriers [-0.1 (0.3) pg mL-1 ] (P = 0.01). CONCLUSIONS: We found that the rs164147 genotype affected the reduction of waist circumference, HOMA-IR, insulin, CRP and IL-6 levels in response to weight loss diet in obese subjects.

Association of G1359A polymorphism of the cannabinoid receptor gene (CNR1) with macronutrient intakes in obese females.

BACKGROUND: The endogenous cannabinoid system plays a role in metabolic aspects of body weight and feeding behaviour. A polymorphism (1359 G/A) (rs1049353) of the CB1 gene was reported as a common polymorphism in the Caucasian population. The present study aimed to investigate the association of the polymorphism (G1359A) of the CB1 receptor gene on macronutrient intake in females with obesity. METHODS: A sample of 896 females was analysed. A bioimpedance measurement, a blood pressure measurement, a serial assessment of nutritional intake with 3 days of written food records, and a biochemical analysis were all performed. The genotype of the CNR1 receptor gene polymorphism (rs1049353) was studied. RESULTS: Five hundred and sixteen patients (57.6%) had the genotype G1359G (non-A carriers) and 380 (42.4%) patients had G1359A (328 patients, 36.6%) or A1359A (52 patients, 5.8%) (A carriers). Triglycerides and high-density lipoprotein (HDL) cholesterol levels were higher in A non-A allele carriers than non-A allele carriers. The intakes of dietary cholesterol and saturated fat for the upper tertile (T3) compared to the baseline tertile were inversely associated with the CB1-R 1359 G/A polymorphism [odds ratio (OR) = 0.59; 95% confidence interval (CI) = 0.30-0.92 and OR = 0.66; 95% CI = 0.39-0.91, respectively]. These data were observed in the second tertile (T2) (OR = 0.61; 95% CI = 0.29-0.94 and OR = 0.58; 95% CI = 0.31-0.90, respectively). CONCLUSIONS: The present study reports an association of the A allele with a better lipid profile (triglycerides and HDL cholesterol) than non-A allele carriers. In addition, this polymorphism is associated with a specific macronutrient intake, as well as with low cholesterol and fat saturated intakes.

Evaluación de las modificaciones genéticas que induce la dieta a través de las células mononucleares sanguíneas / Assessment of the genetic modification inducing diet through blood mononuclear cells

El término nutrigenómica fue creado para describir cómo la nutrición afecta a los genes y a las funciones de la proteínas, a nivel transcripcional, proteómico y metabólico. El uso de las modificaciones en la expresión génica en las células mononucleares sanguíneas (CMNS) podría ser un modelo que permita evaluar los estudios de intervención dietética con el objetivo de comprender los mecanismos subyacentes y la influencia de la dieta y los nutrientes en la aterosclerosis, la resistencia a la insulina, la obesidad y la diabetes mellitus. Existen trabajos que han modificado el aporte dietético de colesterol, grasas poliinsaturadas, grasas monoinsaturadas y antioxidantes, y disminuido el aporte calórico, mostrando una gran variedad de efectos sobre la expresión de RNAm en CMNS de genes relacionados con la inflamación, la inmunidad, el metabolismo lípidico, etc. Estos hallazgos moleculares afianzan el conocimiento sobre la respuesta de nuestro organismo a la dieta y abren la posibilidad del análisis rápido de nuevas vías diagnósticas e incluso de nuevas herramientas terapéuticas (AU)

The term nutrigenomics was created to describe how nutrition affects genes and the functions of the protein, at the transcriptional level, proteomic, and metabolic. Using changes in gene expression in blood mononuclear cells could be a model to assess the dietary intervention studies in order to understand the underlying mechanisms and impact of diet and nutrients in atherosclerosis, resistance insulin, obesity and diabetes mellitus. There are studies that have changed the dietary intake of cholesterol, polyunsaturated fat, monounsaturated, antioxidants and decreased caloric intake showing a variety of effects on the expression of mRNA in blood mononuclear cells related to inflammation, immunity, lipid metabolism genes, etc. These molecular findings entrench awareness of our body’s response to diet and open up the possibility of rapid analysis of new diagnostic pathways in this area of knowledge and even new therapeutic tools (AU)