IL-6 cooperates with peroxisome proliferator-activated receptor-α-ligands to induce liver fatty acid binding protein (LFABP) up-regulation.

BACKGROUND: LFABP plays a critical role in the uptake and intracellular transport of fatty acids (FA) and other peroxisome proliferator-activated receptor alpha (PPARα) ligands. PPARα activation by PPARα ligands bound to LFABP results in gene expression of FA oxidation enzymes and de novo LFABP. The cytokine IL-6 is involved in regulating liver lipid oxidation. AIMS: To study the ability of IL-6 to modulate the expression of the LFABP in hepatocytes. METHODS: HepG2 and mouse primary hepatocytes were used to test LFABP mRNA and protein expression after IL-6 and PPARα-ligand treatments. Mice lacking IL-6 and wild-type C57Bl/6 were subjected to a fasting/re-feeding cycle to monitor hepatic LFABP mRNA kinetics after food intake. RESULTS: In hepatocyte cultures, IL-6 treatment stimulated a LFABP mRNA sustained expression. Combined treatment of IL-6 plus PPARα ligands further enhanced LFABP gene and protein expression. In contrast, pretreatment with the PPARα-antagonist GW-6471 prevented the up-regulation of LFABP mRNA induced by IL-6 in the late phase of LFABP kinetics. Furthermore, the up-regulation of LFABP mRNA observed in the liver of wild-type mice 8 h after re-feeding was absent in mice lacking IL-6. CONCLUSIONS: IL-6 induces LFABP kinetics in hepatocytes and is partially dependent on PPARα. The maximum increase in LFABP expression occurs when the stimulation with IL-6 and PPARα-ligands takes place simultaneously. The in vivo results indicate a postprandial regulation of LFABP that correlates with the presence of IL-6. These effects may have important implications in the postprandial increase in FA uptake and intracellular trafficking in the liver.

Nitric oxide mediates the survival action of IGF-1 and insulin in pancreatic beta cells.

Generation of low levels of nitric oxide (NO) contributes to beta cell survival in vitro. The purpose of this study was to explore the link between NO and the survival pathway triggered by insulin-like growth factor-1 (IGF-1) and insulin in insulin producing RINm5F cells and in pancreatic islets. Results show that exposure of cells to IGF-1/insulin protects against serum deprivation-induced apoptosis. This action is prevented with inhibitors of NO generation, PI3K and Akt. Moreover, transfection with the negative dominant form of the tyrosine kinase c-Src abrogates the effect of IGF-1 and insulin on DNA fragmentation. An increase in the expression level of NOS3 protein and in the enzyme activity is observed following exposure of serum-deprived RINm5F cells to IGF-1 and insulin. Phosphorylation of IRS-1, IRS-2 and to less extent IRS-3 takes place when serum-deprived RINm5F cells and rat pancreatic islets are exposed to either IGF-1, insulin, or diethylenetriamine nitric oxide adduct (DETA/NO). In human islets, IRS-1 and IRS-2 proteins are present and tyrosine phosphorylated upon exposure to IGF-1, insulin and DETA/NO. Both rat and human pancreatic islets undergo DNA fragmentation when cultured in serum-free medium and IGF-1, insulin and DETA/NO protect efficiently from this damage. We then conclude that generation of NO participates in the activation of survival pathways by IGF-1 and insulin in beta cells.

[Physical activity and cardiovascular and metabolic risk factors in general population]. / Actividad física y factores de riesgo cardiovascular y metabólico en la población general.

BACKGROUND AND OBJECTIVE: Our purpose was to evaluate in a cross-section, populational study the association between daily physical activity and various metabolic and cardiovascular disease risk factors. PATIENTS AND METHOD: A total of 1226 randomly selected persons (aged 18-65 years) from a town in southeast Spain were evaluated for studying the association between the level of daily physical activity, both in and out of working hours, and the following variables: body mass index, plasma lipids, hypertension, obesity, altered baseline glycemia, and abnormal glucose tolerance. RESULTS: The intensity of the physical activity at work was related negatively with insulin resistance and levels of LDL cholesterol, and positively with HDL cholesterol. The probability of hypertension, altered baseline glycemia, and abnormal glucose tolerance was greater in those undertaking less daily physical activity. CONCLUSIONS: Daily physical activity, considered as part of the lifestyle, is related with the presence of components of the metabolic syndrome. An increase in daily physical activity should contribute to improve preventible cardiovascular risk factors.

Prevalence of metabolically discordant phenotypes in a mediterranean population-The IMAP study.

OBJECTIVE: To study the prevalence and correlates of body size phenotypes in an adult Spanish population. METHODS: We undertook a cross-sectional analysis in a random sample of 2,270 individuals. We defined six body size phenotypes based on body mass index category (normal-weight, 18.5 to 24.9 kg/m2; overweight, 25 to 29.9 kg/m2; obese, ≥30.0 kg/m2) and the presence of ≤1 (metabolically healthy) or ≥2 (metabolically abnormal) cardiometabolic abnormalities: metabolically healthy normal-weight (MHNW), metabolically abnormal normal-weight (MANW), metabolically healthy overweight (MHOW), metabolically abnormal overweight (MAOW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). We considered four cardiometabolic abnormalities: systolic and/or diastolic blood pressure ≥130/85 mm Hg, triglycerides ≥150 mg/dL, high-density-lipoprotein cholesterol levels <40/<50 mg/dL in men/women, and elevated glucose (fasting plasma glucose ≥100 mg/dL or previous diabetes). RESULTS: The prevalence of the MHO, MHOW, and MANW phenotypes was 2.2, 13.9, and 7.9%, respectively. Whereas 9.6% of obese and 32.6% of overweight individuals were metabolically healthy, 21.3% of the normal-weight subjects were metabolically abnormal. A multivariate regression model (adjusted for age, sex, and waist circumference) showed that age >40 years, male sex, and higher waist circumference were independently associated with the metabolically abnormal phenotype MANW, whereas younger age, female sex, and lower waist circumference were independently associated with the metabolically healthy phenotypes. CONCLUSION: The prevalence of MHO in our population is low and is more common in women and younger people. In contrast, a high proportion of normal-weight individuals (mainly over 40 years of age) in our population show cardiometabolic abnormalities.

The -30G>A polymorphism of the glucokinase gene promoter is associated with obesity in a population from southern Spain.

The aim of this study was to test the hypothesis of an association between the -30G>A polymorphism of the promoter of the glucokinase gene and the prevalence and incidence of obesity. We studied the -30G>A polymorphism of the glucokinase gene promoter in 981 persons, of whom 866 were seen again 6 years later. All the persons underwent an oral glucose-tolerance test and the BMI (weight/height(2)) was recorded. The -30G>A polymorphism of the glucokinase gene promoter was studied using RFLP-PCR. At the initial study, the probability of having a BMI > or =25 in carriers of the A allele was significantly lower than expected by chance (odds ratio (OR) = 0.63; 95% confidence interval (CI) = 0.456-0.885). In those persons with a BMI > or =30 at the first study, the probability at 6 years of losing weight (reaching a BMI < 30) was greater in carriers of the A allele (OR = 0.22; 95% CI = 0.087-0.576). The increase in weight over these 6 years, taken as a continuous variable, was significantly less only in those persons who were originally obese (P = 0.018). In conclusion, in a population from southern Spain, carriers of the A allele of the -30G>A polymorphism in the promoter of the glucokinase gene had a lower risk for obesity and the likelihood of losing weight was greater in those obese persons who had the A allele (GA or AA).