The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome., F. Schinzari, M. Tesauro, C. Cardillo., and Seznam literatury
Obstructive sleep apnoea (OSA) has been associated with disturbances in energy metabolism and insulin resistance,nevertheless, the links between OSA severity, resting energy expenditure (REE) and insulin resistance (homeostasis model assessment, HOMA-IR) remained unexplored Therefore, we investigates the effects of OSA severity on REE, and relationships between REE and HOMA-IR in patients with OSA. Forty men[mean (SD) age 49.4 (11.4) years] underwent overnight polysomnography; REE was assessed using indirect calorimetry. REE adjusted for fat -free mass (FFM) was higher in patients with moderate-to severe OSA [n=24; body mass index (BMI) 31.1(2.7) kg.m-2; apnoea-hypopnoea index (AHI) ≥15 episodes.h-1] compared to participants with no clinically significant OSA(n=16; BMI 30.3 (2.2) kg.m-2; AHI<15 episodes.h-1) [median (interquartile range) 30.4 (26.1-31.3) versus 25.8 (24.6-27.3) kcal.kg-1.24 h-1, p=0.005)]. AHI and oxygen desaturation index(ODI) were directly related to REE/FFM (p=0.001; p<0.001, respectively) and to HOMA-IR (p<0.001 for both). In stepwise multiple linea models,REE/FFM was independently predicted by ODI (p<0.001) and age(p=0.028) (R2=0.346); HOMA-IR wasindependently predicted by ODI only (p<0.001,R2=0.457). In conclusion, male patients with moderate-to severe OSA haveincreased REE paralleled by impaired insulin sensitivity. Severity of nocturnal intermittent hypoxia reflected by ODI is an independent predictor of REE/FFM and HOMA-IR.
An ethanol vapor concentration of 1.6 mmol/l was used to test the diurnal variations of the olfactory response in two groups of snails, which were adapted to different light-dark cycles. The results revealed that the olfactory sensitivity to stimulation with ethanol was significantly increased during the day-time, which corresponds to the scotophase of the light-dark cycle, to which the animals had been adapted (c2-test, P < 0.01)., M. Voss, C. Büchert, C. Missfelder., and Obsahuje bibliografii
Few investigators have simultaneously evaluated leptin, soluble leptin receptor (SLR) and leptin gene polymorphisms in preeclampsia cases and controls.We examined these three biomolecular markers in 40 preeclampsia cases and 39 controls.Plasma leptin and SLR concentrations were determined using immunoassays. Genotype for the tetranucleotide
repeat (TTTC)n, polymorphism in the 3′-flanking region of the leptin gene was determined using PCR.Alleles of the polymorphism were characterized by size distributions [short repeats (class I); and long repeats (class II)].Logistic regression was used to calculate odds ratio
s (OR) and 95 % confidence intervals (CI).Leptin concentrations were
higher in our cases than in the controls (53.1±4.7 vs. 17.7±2.4 ng/ml,p<0.05).
SLR concentrations were slightly lower in our patients than in the controls (25.7±1.9 vs. 29.1±1.1 ng/ml, p>0.05). Elevated leptin (≥ 14.5 ng/ml) was associated with a 3.8-fold (CI 1.0-14.4) increased risk; whereas low SLR (< 28.5 ng/ml) was associated with a 6.3-fold (CI 1.7-23.2) increased risk of preeclampsia. The I/II genotype was associated with a 3.8-fold increased risk of preeclampsia (OR=3.8; 95 % CI 0.8-18.0); and the II/II genotype was not observed among our cases (0 % vs. 33 % p<0.001). Larger studies would be needed to confirm and further clarify the relations between functional variants in the leptin gene and preeclampsia risk.
Renal medullary endothelin B receptors (ETB) mediate sodium excretion and blood pressure (BP) control. Several animal models of hypertension have impaired renal medullary ETB function. We found that 4-week high-caloric diet elevated systolic BP in Dahl salt-sensitive (Dahl S) rats (126±2 vs. 143±3 mm Hg, p<0.05). We hypothesized that renal medullary ETB function is dysfunctional in DS rats fed a high-caloric diet. We compared the diuretic and natriuretic response to intramedullary infusion of ETB agonist sarafotoxin 6c (S6c) in DS rats fed either a normal or high-caloric diet for 4 weeks. Urine was collected during intramedullary infusion of saline for baseline collection followed by intramedullary infusion of either saline or S6c. We first examined the ETB function in DS rats fed a normal diet. S6c increased urine flow (2.7±0.3 μl/min during baseline vs. 5.1±0.6 μl/min after S6c; p<0.05; n=5) and sodium excretion (0.28±0.05 vs. 0.81±0.17 μmol/min; p<0.05), suggesting that DS rats have renal medullary ETB function. However, DS rats fed a high-caloric diet displayed a significant increase in urine flow (2.7±0.4 vs. 4.2±0.4 μl/min, baseline vs. S6c infusion, respectively; p<0.05, n=6), but no significant change in sodium excretion in response to S6c (0.32±0.06 vs. 0.45±0.10 μmol/min). These data demonstrate that renal medullary ETB function is impaired in DS rats fed a high-caloric diet, which may be contributed to the elevation of blood pressure during high-caloric feeding in this model., W. Kittikulsuth, K. A. Hyndman, J. S. Pollock, D. M. Pollock., and Seznam literatury
To investigate the relationship between development of obesity and the small intestinal functions two experimental models of male Wistar rats were used in the present work: 1) early postnatally overfed rats, nursed from birth to weaning in small litters (SL, 4 pups/nest), and 2) neonatally monosodium glutamate treated rats (MSG 2 mg/g b.w. administered s.c. for 4 days after birth) submitted to the same early nutritional manipulation. After weaning, all animals had free access to a standard pellet diet and at 40 and 80 days of age their body weight, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP) activity were compared with parameters of the offsprings raised under normal feeding conditions (NL, 8 pups/nest). At 40 and 80 days of age the postnatally overfed pups from SL nests became heavier, displayed a significantly increased epididymal plus retroperitoneal fat pad weight (P<0.01) and significantly higher AP activity in both segments of the small intestine (P<0.01) in comparison with rats nursed in NL nests, although their mean daily food intake did not differ from that of non-obese rats during the postweaning periods examined. In contrast, the same treatment of MSG rats had only a small effect on late appearance of obesity, i.e. in early postnatally overfed and normally fed MSG rats a similar pattern of body weight, food intake, adiposity and AP activity was found after weaning. The effect of MSG-treatment was also accompanied by the appearance of normophagia, hypophagia and stunted growth on day 40 and day 80, respectively. Moreover, the size of fat depots and the increase of brush-border-bound AP activity in MSG rats belonging to the SL and NL groups was quantitatively similar to the values size of these parameters observed in SL obese rats subjected to early postnatal overnutrition. These results indicate that postnatal nutritional experience (overnutrition) may represent a predisposing factor in control rats from small litters for the development of obesity in later life. Permanently increased small intestinal AP activity observed after weaning in both models of obesity when hyperphagia is not present suggest that these functional changes and associated alterations in food digestion could be a component of regulatory mechanisms contributing to the maintenance of their elevated body fat weight.
Peroxisome proliferator-activated receptors (PPAR) belong to the nuclear receptor superfamily of ligand-activated transcription factors. PPAR-α
, first of its three subtypes (α, β, γ) has traditionally been considered an important regulator of lipid metabolism while its role in the regulation of insulin sensitivity has not been recognized until recently. Here we summarize the experimental and clinical studies focusing on the role of PPAR-α in the regulation of insulin sensitivity. In most of the experimental studies the activation of PPAR-α in rodents leads to improvement of insulin sensitivity by multiple mechanisms including improvement of insulin signaling due to a decrease of ectopic lipids in
non-adipose tissues and decrease of circulating fatty acids and triglycerides
. In contrast, the effect of PPAR-α agonist in humans is much less pronounced probably due to a lower expression of PPAR-α relative to rodents and possibly other mechanisms. Further clinical studies using more potent PPAR-α agonists on a larger population need to be performed to
evaluate the possible role of PPAR-α in the regulation of insulin sensitivity in humans.
Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m2) and obese patients (BMI>35 kg/m2). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4.48±0.19 ng/ml vs. 6.63±0.29 ng/ml; p<0.001, KISS: 1.357±0.15 nmol/l vs. 2.165±0.174 nmol/l; p<0.01). SPX negatively correlated with BMI, HOMA-IR, insulin, glucagon, active ghrelin and leptin. Positive correlations were found between SPX and QUICKI index, McAuley index, serum levels of obestatin, GLP-1 and adiponectin and orexin-A Serum KISS negatively correlated with BMI, HOMA-IR, serum levels of insulin, glucagon, active ghrelin and leptin. KISS positively correlated with QUICKI index, McAuley index and adiponectin. In summary, SPX and KISS show negative correlations with obesity, insulin resistance indices, and hormones known to affect insulin sensitivity in females. Both, SPX and KISS could be therefore relevant in the pathophysiology of obesity and insulin resistance., P. A. Kołodziejski, E. Pruszyńska-Oszmałek, E. Korek, M. Sassek, D. Szczepankiewicz, P. Kaczmarek, L. Nogowski, P. Maćkowiak, K. W. Nowak, H. Krauss, M. Z. Strowski., and Seznam literatury
In addition to a number of deleterious effects on cellular integrity and functions, diabetic metabolic milieu has been implicated in a rapidly growing number of alterations in signal transduction. In this review we focus on Akt kinase physiology, its alterations in diabetes mellitus (DM), and on the emerging role of this signaling system in the pathophysiology of diabetic microvascular complications. Studies focusing on Akt in diabetes suggest both decrease and increase of Akt activity in DM. Alterations of Akt activity have been found in various tissues and cells in diabetes depending on experimental and clinical contexts. There is convincing evidence suggesting defective Akt signaling in the development of insulin resistance. Similar defects, as in insulin-sensitive tissues, have been reported in endothelia of DM Type 2 models, possibly contributing to the development of endothelial dysfunction under these conditions. In contrast, Akt activity is increased in some tissues and va
scular beds affected by complications in DM Type 1. Identification of the role of this phenomenon in DM-induced growth and hemodynamic alterations in affected vascular beds remains one of the major challenges for future research in this area. Future studies should include the evaluation of
therapeutical benefits of pharmacological modulators of Akt activity.
Obesity is increasing at an alarming rate globally. Several studies have shown that premenopausal women have a reduced risk of CV disease and a reduced myocardial susceptibility to ischemia/reperfusion injury. The effect of obesity on myocardial tolerance to ischemia in women has not been established. To determine how obesity affects myocardial susceptibility to ischemia/reperfusion injury in both males and females, we fed male and female Wistar rats a high caloric diet (HCD) or a control rat chow diet (CD) for 18 weeks. Rats were subsequently fasted overnight, anesthetized and blood was collected. In separate experiments, 18-week-fed (HCD and CD) rats underwent 45 min in vivo coronary artery ligation (CAL) followed by 2 hours reperfusion. Hearts were stained with TTC and infarct size determined. Both male and female HCD fed rats had increased body and visceral fat weights. Homeostasis model assessment (HOMA) index values were 13.95±3.04 for CD and 33.58±9.39 for HCD male rats (p<0.01) and 2.98±0.64 for CD and 2.99±0.72 for HCD fed female rats. Male HCD fed rats had larger infarct sizes than CD fed littermates (43.2±9.3 % vs. 24.4±7.6 %, p<0.05). Female HCD and CD diet fed rats had comparable infarct sizes (31.8±4.3 % vs. 23.9±3.3 %). We conclude that male rats on the HCD became viscerally obese, dyslipidemic and insulin-resistant, while female HCD fed rats became viscerally obese without developing dyslipidemia or insulin resistance. Obesity increased myocardial infarct size in males but not the females., C. Clark ... [et al.]., and Obsahuje seznam literatury