Manuel Gonzalez Sagrado

Circulating visfatin in obese non-diabetic patients in relation to cardiovascular risk factors, insulin resistance, and adipocytokines: a contradictory piece of the puzzle.

OBJECTIVE Obesity and insulin resistance are associated with cardiovascular risk factors. The aim of the present study was to explore the relation of circulating visfatin to insulin resistance, cardiovascular risk factors, anthropometry, and adipocytokines in obese patients without diabetes mellitus. METHODS A population of 228 obese non-diabetic outpatients was analyzed in a prospective way. All patients with a 2-wk weight-stabilization period before recruitment were enrolled. Biochemical analysis and nutritional evaluation were performed. RESULTS Subjects were 62 men (27.2%) and 166 women (62.8%) with a mean age of 41.1 ± 16.4 y and a mean body mass index of 35.8 ± 3.6 kg/m(2). Patients were divided in two groups by median visfatin value (22.8 ng/mL), i.e., those with low values (group I) and those with high values (group II). Patients in group I had greater weight, body mass index, fat mass, fat-free mass, insulin, homeostasis model of assessment, triacylglycerol, leptin, and adiponectin than patients in group II. Patients in group II had higher total cholesterol, low-density lipoprotein cholesterol, resistin, and tumor necrosis factor-α levels than patients in group I. In a multivariate analysis with age- and sex-adjusted basal visfatin concentration as a dependent variable, only weight and leptin remained as an independent predictor in the model (F = 6.5, P < 0.05), with an inverse correlation. CONCLUSION Total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, and resistin levels are elevated in patients with visfatin levels above the median value. Homeostasis model of assessment, insulin, weight, fat mass, fat-free mass, triacylglycerols, leptin, and adiponectin are decreased in these patients.

Influence of Ala54Thr polymorphism of fatty acid–binding protein-2 on clinical results of biliopancreatic diversion

OBJECTIVE Bariatric surgery is the most effective long-term treatment for morbid obesity, reducing obesity-associated comorbidities. The purpose of the present study was to evaluate the fatty acid-binding protein-2 Ala54Thr polymorphism outcomes 1 y after biliopancreatic diversion in morbidly obese patients. METHODS A sample of 41 morbidly obese patients (body mass index >40 kg/m(2)) were operated upon from December 2004 to December 2006. Weight, fat mass, blood pressure, basal glucose, triacylglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured at the basal visit and at each visit. The frequency of patients with diabetes mellitus, hypertension, and hyperlipidemia was recorded at each visit. RESULTS Twenty-three patients (56.1%) had genotype Ala54/Ala54 (wild group) and 18 patients had genotype Ala54/Thr54 (15 patients, 36.5%) or Thr54/Thr54 (3 patients, 7.4%; mutant group). In the wild group, body mass index, weight, fat mass, systolic blood pressure, glucose, total cholesterol, low-density lipoprotein cholesterol, and triacylglycerol concentrations decreased. Diastolic blood pressure remained unchanged. In the mutant group, the same parameters improved, without statistical differences from the wild group. Initial excess weight percent loss at 1 y of follow-up was similar in both genotype groups (61.8% versus 61.9%, NS). CONCLUSION Polymorphism Ala54Thr of fatty acid-binding protein did not have an effect on weight loss or clinical outcomes after bariatric surgery.

Evaluation of weight loss and adipocytokines levels after two hypocaloric diets with different macronutrient distribution in obese subjects with rs9939609 gene variant.

Common polymorphisms of the fat mass and obesity associated gene (FTO) have been linked to obesity in some populations. One of these genetic variants (rs9939609) has been related to an increased risk of obesity.

Influence of G1359A polymorphism of the cannabinoid receptor gene on anthropometric parameters and insulin resistance in women with obesity.

A silent polymorphism (1359 G/A) of the cannabinoid receptor gene was reported as a common polymorphism in white populations. The aim of our study was to investigate the influence of this polymorphism (G1359A) of cannabinoid receptor gene on obesity, insulin resistance, and adipocytokines in women with obesity. A population of 290 women was analyzed. Indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure measurement, serial assessment of nutritional intake with 3-day written food records, and biochemical analysis were performed. One hundred fifty-nine patients (54.8%) had the genotype G1359G (wild-type group), and 131 (45.2%) patients had G1359A (116 patients, 40.0%) or A1359A (15 patients, 5.2%) (mutant-type group). Triglycerides (122.3 ± 65.9 vs 107.2 ± 44.8 mg/dL, P < .05), insulin (15.8 ± 9.4 vs 13.6 ± 6.9 mUI/L, P < .05), and homeostasis model assessment values (3.85 ± 2.2 vs 3.33 ± 1.9, P < .05) were higher in the wild-type group than the mutant-type group. High-density lipoprotein cholesterol levels (56.8 ± 24.1 vs 58.3 ± 13.9 mg/dL, P < .05) were higher in the mutant-type group than the wild-type group. The novel finding of this study is the association of the mutant-type group G1359A and A1359A with a better cardiovascular profile (triglyceride, high-density lipoprotein cholesterol, insulin, and homeostasis model assessment levels) than the wild-type group.

Resistin levels in morbid obese patients following the biliopancreatic diversion surgery.

Previous studies addressing the changes of resistin concentrations in morbidly obese patients after bariatric surgery have yielded conflicting results. The purpose of the present study was to investigate the changes in serum resistin levels 1 year after biliopancreatic diversion in morbidly obese patients without diabetes mellitus. A cohort of 39 morbidly obese patients without diabetes mellitus was operated. Biochemical and anthropometric evaluation were realized at basal visit and at each visit. The frequency of patients with hypertension and hyperlipidemia was recorded at each visit. Overall the mean patient age was 44.8 ± 14.1, and the mean preoperative BMI was 47.3 ± 6.5 kg/m². After one year of surgery, a significant decrease was observed in BMI, weight, waist circumference, fat mass, blood pressure, total cholesterol, LDL cholesterol, and triglyceride levels. Resistin levels did not change after surgery (5.61 ± 1.93 ng/ml vs. 6.41 ± 3.58 ng/ml; ns). Correlation analysis showed a positive association between basal resistin and weight (r = 0.68, p < 0.01) and fat mass (r = 0.65, p < 0.05). Resistin concentrations did not change after massive weight loss with biliopancreatic diversion in morbid obese patients without diabetes mellitus.

Changes of ghrelin and leptin in response to hypocaloric diet in obese patients

OBJECTIVE Hypocaloric diet-induced weight loss produces a coordinated decrease in plasma leptin levels and an increase in plasma ghrelin levels. The aim of the present study was to determine whether subjects who lose significant weight experience changes in circulating ghrelin and leptin levels. METHODS A population of 66 obese patients was analyzed. Leptin, active ghrelin blood levels, and other cardiovascular risk factors were measured before and after 3 mo of a hypocaloric diet. RESULTS Sixty-six patients (17 male, 49 female) gave informed consent and were enrolled in the study. Forty-six patients did not lose 5% of initial weight (group I, weight loss 1.4 +/- 2.5 kg) and 20 patients lost weight (>5% of initial weight; group II, weight loss 7.1 +/- 2.6 kg). In group I, active ghrelin levels increased (7.40 +/- 8 versus 19.40 +/- 32 pg/mL, P < 0.05) and leptin levels decreased (102.6 +/- 86 versus 89.30 +/- 76 ng/mL, P < 0.05). In group II, leptin levels also decreased significantly (69.80 +/- 67 versus 53.50 +/- 59 ng/mL, P < 0.05). Active ghrelin in this group did not show differences (24.20 +/- 41 versus 10.30 +/- 12 pg/mL, NS). In the multivariate analysis with a dependent variable (change in active ghrelin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and basal intake of protein remained in the model. In the multivariate analysis with a dependent variable (change in leptin levels, pg/ml) in group II adjusted by age and sex, only basal fat mass and BMI remained in the model. CONCLUSION Patients with weight loss secondary to a hypocaloric diet did not change active ghrelin levels and decreased leptin levels after treatment.

The rs9939609 Gene Variant in FTO Modified the Metabolic Response of Weight Loss After a 3-Month Intervention With a Hypocaloric Diet

Background Common polymorphisms in the fat mass and obesity associated gene (FTO) have been linked to obesity in some populations. Nevertheless, the role of FTO variants on body weight response after dietary intervention remains equivocal. Objective We decided to analyze the effects of the rs9939609 FTO gene polymorphism on body weight changes and metabolic parameters after 3 months of a hypocaloric diet. Design Before and after 3 months on a low-fat hypocaloric diet, a white population of 106 subjects with obesity was analyzed. Results Of the study subjects, 35 (33%) had the genotype TT and 71 (67%) had the next genotypes; TA (46 study subjects, 43.4%) or AA (25 study subjects, 23.6%). After dietary treatment and in TT group, weight, waist circumference, total cholesterol, LDL-cholesterol, insulin, and homeostasis model assessment decreases were less than subjects carrying the A allele [−3.1 (3.6) vs −2.4 (4.1) kg: P < 0.05], waist circumference [−5.4 (6.4) vs −2.6 (4.8) cm; P < 0.05], total cholesterol [−12.3 (35.3) vs −6.4 (4.7) mg/dL; P < 0.05], LDL-cholesterol [−22.3 (30.5) vs −10.7 (30.5) mg/dL; P < 0.05], insulin [−1.89 (5.5) vs +0.94 (8.2) mUI/L; P < 0.05], and homeostasis model assessment [−0.46 (1.11) vs −0.01 (2.4); P < 0.05]. Conclusions Our study confirmed a higher weight loss in A carriers of FTO rs9939609 polymorphism than in TT genotype study subjects.

Effects of C358A missense polymorphism of the degrading enzyme fatty acid amide hydrolase on weight loss, adipocytokines, and insulin resistance after 2 hypocaloric diets

It has been demonstrated that the polymorphism 385 C/A of fatty acid amide hydrolase was associated with obesity. We decided to investigate the role of a polymorphism (cDNA 385 C->A) on insulin resistance and weight loss secondary to a low-fat vs a low-carbohydrate diet. A population of 248 patients with obesity was analyzed. Basal measurements were performed, and values were compared to those at the end of a 3-month period in which subjects received either diet I (low fat) or diet II (low carbohydrate). One hundred seventy-eight patients (71.8%) had the genotype C358C (wild-type group), and 70 (28.2%) patients had the genotype C358A (62 patients, 25%) or A358A (8 patients, 3.2%) (mutant-type group). With diet I, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased in the wild-type and mutant-type groups. With diet II, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased in both genotypes. With diet I, leptin, glucose, total cholesterol, triglyceride, insulin, and homeostasis model assessment for insulin sensitivity (HOMA) decreased in the wild-type group. In the mutant-type group, only cholesterol decreased in a significant way. With diet II, leptin, interleukin-6, glucose, total cholesterol, low-density lipoprotein cholesterol, insulin, HOMA, and C-reactive protein decreased in the wild-type genotype. The allele A358 of fatty acid amide hydrolase was associated with a lack of improvement on glucose insulin, HOMA, and leptin levels in both diets after weight loss.

Modulation of adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients by -55CT polymorphism of UCP3 gene.

Decreased expression or function of UCP3 (uncoupling protein 3) could reduce energy expenditure and increase the storage of energy as fat. Some studies have pointed to a role of UCP3 in the regulation of whole body energy homeostasis, diet induced obesity, and regulation of lipids as metabolic substrates. The C/C genotype of a polymorphism in the UCP3 promoter (-55C-->T) is associated with an increased expression of UCP3 mRNA in muscle. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene on adipocytokines response and weight loss secondary to a hypocaloric diet in obese patients. A population of 107 obese (body mass index >30) nondiabetic outpatients was analyzed in a prospective way. Before and after three months of a hypocaloric diet, an indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3-day written food records, and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of lipids and 23% of proteins). The exercise program consisted of aerobic exercise for at least 3 times per week (60 minutes each). The mean age was 49.5+/-34.5 years and the mean BMI 34.5+/-4.8, with 27 males (25.3%) and 80 females (74.7%). Ninety patients (25 males/65 females) (83.6%) had the genotype 55CC (wild group) and 17 patients (2 male/15 females) (16.4%) 55CT (mutant group). The percentage of responders (weight loss) was similar in both groups (wild group: 84.7% vs. mutant group: 81.8%). BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, and waist-to-hip ratio decreased in the wild group and RMR and VO (2) were increased. In the mutant group, BMI and weight decreased. Leptin and IL-6 levels have a significant decrease in the wild group (9.6%: p<0.05) and (30.5%: p<0.05), respectively. Patients with -55CC genotype have a significant decrease in leptin, interleukin 6, BMI, weight, fat mass, systolic blood pressure, LDL cholesterol, waist circumference, waist-to-hip ratio weight, fat mass, and systolic blood pressure.

Effects of duodenal-jejunal exclusion on beta cell function and hormonal regulation in Goto-Kakizaki rats

BACKGROUND The aim of our work was to investigate the hormones that control glycemic status and in vitro β-cell function in diabetes mellitus after a duodenal-jejunal exclusion in Goto-Kakizaki rats (Taconic, Denmark). METHODS Twenty-three rats (age, 12-14 wk) were randomized as follows: group 1 (n = 14), no intervention (control); or group 2 (n = 9), duodenal-jejunal exclusion. RESULTS In group 2, levels of glucagon and leptin were lower than in group 1 at 1 week and at 8 weeks. Glucagon-like peptide 1 levels had a significant increase at 8 weeks from basal value in group 2 and this value was higher than in group 1. The insulin secretion at 60 minutes in group 2 was higher than in group 1 (group 1, 12.9 ± 12.0 μg/L vs group 2, 41.9 ± 36.3 μg/L; P < .05). Messenger RNA (mRNA) expression of insulin at 2 months was higher in the rat pancreas of the experimental group than in the control group (group 1, .99 ± .48 mRNA amount vs group 2, 1.66 ± .33 mRNA amount; P < .05). CONCLUSIONS Gastrojejunal bypass in this model improves glucose ratios, with a significant increase of glucagon-like peptide 1 and decrease of homeostasis model assessment, glucagon, and leptin levels after surgery. This type of surgery improves mRNA insulin expression in pancreatic islets and insulin secretion as well.