Carotid intima-media thickness is predicted by combined eotaxin levels and severity of hepatic steatosis at ultrasonography in obese patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) is a distinct coronary artery disease (CAD) risk factor. The atherosclerotic process predisposing to CAD includes altered lipid profile and inflammatory processes. The available evidence suggests that increased circulating levels of eotaxin, an eosinophil chemoattractant cytokine implicated in allergic responses, are detected in the serum of patients with CAD. Relationships were sought between serum eotaxin on the one hand, and intima-media thickness--an early predictor of the atherosclerotic process, hepatic steatosis, arterial blood pressure values, as well as inflammation/immune markers and angiogenetic factors--on the other. METHODS: Eighty obese patients with NAFLD, diagnosed at ultrasonography, without evident cytolysis, formed our study population. Anthropometric measures, metabolic profile, serum concentrations of interleukin-1ß, C-reactive protein, interleukin-6, fibrinogen, ferritin, TNF-α, spleen size, vascular endothelial growth factor, platelet-derived growth factor-BB and heat shock protein-70 were evaluated. RESULTS: Serum eotaxin concentrations were distinctly associated with TNF α, IL-6, IL-1ß, VEGF and PDGF-BB levels but not with CRP, fibrinogen, heat shock protein-70 or spleen size. Among the metabolic and anthropometric parameters, a significant predictive power emerged when comparing eotaxin to insulin resistance, expressed as HOMA. NAFLD was distinctly associated with HOMA (P = 0.0005). Intima-media thickness was well predicted by both eotaxin levels and severity of NAFLD at ultrasonography, although no relation was detected between these last two variables. DISCUSSION AND CONCLUSION: A role for insulin resistance in mediating the interplay between eotaxin and other inflammation/immune parameters could be evidenced in the induction/maintenance of atherosclerosis of obese patients with NAFLD.

Is serum Interleukin-17 associated with early atherosclerosis in obese patients?

Atherosclerosis is a chronic inflammatory process of the vessel walls, and CD4+ T-cells are peculiar to both human and murine atherosclerotic lesions. There is a recent line of research favoring hypothetic allergic mechanisms in the genesis of atherosclerosis and, consequently, coronary artery disease (CAD), among which Interleukin (IL)-17 appears to be a key cytokine regulating local tissue inflammation. The objective was to add a piece of information on the role of IL-17 in the genesis of atherosclerosis. Eighty obese patients with normal liver enzyme levels but presenting with ultrasonographic evidence of NAFLD formed the population of this cross-sectional study. Anthropometric measures, data on excess adiposity, metabolic profile, serum concentrations of IL-17, eotaxin-3, IL-8, and CCL4/MIP1ß, C-reactive protein, fibrinogen, ferritin, TNF-α, as well carotid intima-media thickness (IMT), a marker of atherosclerosis, and the main risk factors for CAD, such as blood pressure and smoking status, but also less determinant ones such as degree of NAFLD severity, Intramuscular Triglyceride storage and Resting Metabolic Rate were evaluated. Serum concentrations of Il-17 were detected as related to those of inflammatory cytokines, IL-6, IFN-γ and TNF-α. Furthermore, circulating levels of IL-17 were linked to those mirroring allergic process, IL-8, CCL4/MIP1ß and eotaxin. Early atherosclerosis, evidenced as increased IMT, was not associated with circulating IL-17 levels. At multiple regression,IMT was predicted, other than by age, by the amount of the visceral adiposity, expressed as visceral adipose tissue at ultrasonography, and by serum eotaxin. In conclusion, a strong relationship was found between the IL-17-related chemokine eotaxin and IMT. The association found between the amount of visceral fat and circulating levels of eotaxin on the one hand, and IMT on the other, could reinforce the hypothesis that IL-17, released by the visceral adipose tissue, induces eotaxin secretion via the smooth muscle cells present in the atheromatosus vessels.

Should visceral fat be reduced to increase longevity?

Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity.

Are hepatic steatosis and carotid intima media thickness associated in obese patients with normal or slightly elevated gamma-glutamyl-transferase?

BACKGROUND: Hepatic steatosis (HS) has been associated with obesity and metabolic syndrome (MS), conditions carrying a high risk of coronary artery disease. We aimed to determine whether HS was an independent factor of atherogenic risk beyond its association with MS and its components. METHODS: We assessed the circulating levels of the heat shock protein-70 (HSP-70), a chaperone involved in inflammation, endoplasmic reticulum stress and apoptosis at liver and endothelial level and the gamma-glutamyl transferase activity (γ-GT) correlating them to carotid intima-media thickness (IMT), along with lipid profile, HOMA, C-reactive protein, fibrinogen, ferritin, adiposity type as well as spleen volume in 52 obese pts with grade 1, 128 with grade 2, and 20 with grade 3 of HS evaluated by sonography. RESULTS: Patients with different grade of HS demonstrated overlapping HSP-70 levels; similarly performed obese subjects regarding IMT. Using multiple regression analysis, IMT was predicted by age, visceral adiposity and by HOMA (ß = 0.50, p < 0.0001, ß = 0.30, p = 0.01 and ß = 0.18, p = 0.048 respectively, while the severity of HS was predicted by visceral and subcutaneous adiposity and HOMA (ß = 0.50, p < 0.0001 and ß = 0.27, p = 0.001 and ß = 0.18, p = 0.024, respectively). CONCLUSION: In our series of patients with normal or mild elevation of γ-GT, the severity of HS does not entail higher IMT, which may be linked to MS stigmata.

Physical activity: an important adaptative mechanism for body-weight control.

We review the current concepts about energy expenditure and evaluate the physical activity (PhA) in the context of this knowledge and the available literature. Regular PhA is correlated with low body weight and low body fat mass. The negative fat balance is probably secondary to this negative energy balance. Nonexercise activity thermogenesis (NEAT) and physical activity, that is crucial for weight control, may be important in the physiology of weight change. An intriguing doubt that remains unresolved is whether changes in nutrient intake or body composition secondarily affect the spontaneous physical activity.