Adipose tissue-produced hormones significantly affect the metabolism of lipids and carbohydrates as well as numerous other processes in human body. It is generally accepted that endocrine dysfunction of adipose tissue may represent one of the causal links between obesity and insulin resistance/diabetes. Epidemiological studies underlined that obesity represents a significant risk factor for the development of cancer, although the exact mechanism of this relationship remains to be determined. Multiple recent studies have indicated that some of adipose tissue-derived hormones may significantly influence the growth and proliferation of tumorous stroma and malignant cells within. Here we review current knowledge about possible relationship of leptin and adiponectin to the etiopathogenesis of different malignant tumors. Most of the studies indicated that while leptin may potentiate the growth of cancer cells in vitro, adiponectin appears to have an opposite effect. Further studies are necessary to decide whether obesity-induced endocrine dysfunction of adipose tissue can directly influence carcinogenesis in different tissues and organs.
It is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered protein produced exclusively by adipocytes. A number of studies have shown that obesity, insulin resistance and atherosclerosis are accompanied by decreased adiponectin levels and that adiponectin replacement under experimental settings is able to diminish both insulin resistance and atherosclerosis. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of adiponectin and to discuss its potential in the treatment of insulin resistance and atherosclerosis.
Insulin resistance is present in patients with Type 2 diabetes mellitus as well as in obese patients without diabetes. The aim of our study was to compare insulin action in diabetic and control persons with or without obesity and to evaluate the influence of serum cholesterol, serum triglyceride and blood pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg.m-2, and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique was performed at an insulin infusion rate of 1 mU.kg-1.min-1 during 120 min. We evaluated the metabolic clearance rate of glucose (MCRG, ml.kg-1.min-1) as the most important indicator of insulin action by isoglycemic clamp. The Pearson's correlation and multiple regression models were used to compare studied factors with the insulin action. We found following predictors of insulin resistance expressed in the relationship with MCRG: BMI (r = -0.68, p<0.001), plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55, p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38, p<0.01). From the multiple regression analysis we conclude that obesity may have even greater influence on the insulin action than diabetes mellitus itself., G. Šindelka, J. Škrha, M. Prázný, T. Haas., and Obsahuje bibliografii
The increased prevalence of obesity in children and its complications have led to a greater interest in studying baroreflex sensitivity (BRS) in children. This review of BRS in children and adolescents includes subtopics on: 1. Resting values of BRS and their reproducibility, 2. Genetics of BRS, 3. The role of a primarily low BRS and obesity in the development of hypertension, and 4. Association of diabetes mellitus, BRS, and obesity. The conclusions specific to this age follow from this review: 1. The mean heart rate (HR) influences the measurement of BRS. Since the mean HR decreases during adolescence, HR should be taken into account. 2. A genetic dependency of BRS was found. 3. Low BRS values may precede pathological blood
-pressure elevation in children with white-coat hypertension. We hypothesize that low BRS plays an active role in the emergence of hypertension in youth. A contribution of obesity to the development of
hypertension was also found. We hypothesize that both factors, a primarily low BRS and obesity, are partially independent risk factors for hypertension in youths. 4. In diabetics, a low BRS compared to healthy children can be associated with insulin resistance. A reversibility of the BRS values could be possible after weight loss.
We investigated the potential role of magnesium (Mg) dysbalance in the pathogenesis of insulin resistance (IR) in patients with mildly-to-moderately decreased renal function (creatinine: 142.8±11.0 mmol/l). The data were compared to those of 8 age- and sex-matched healthy controls (CTRL). The standard oral glucose tolerance test (oGTT) was performed in 61 patients. Twenty-two patients were classified as IR according to their values on fasting and after-load immunoreactive insulin concentrations. Serum and total erythrocyte Mg (tErMg) (atomic absorption spectro-photometry) and free erythrocyte Mg (fErMg) concentrations (31P NMR spectroscopy) were determined prior to and two hours after the glucose load. Ten out of 39 insulin-sensitive (IS) patients, but only one out of 22 insulin-resistant (IR) patients, had a low basal fErMg concentration (<162.2 mmol/l, c2, p<0.01). IR patients had higher serum Mg, total erythrocyte Mg and bound erythrocyte Mg (bErMg) concentrations (both before and after glucose load) when compared with the IS group. Both groups responded to the glucose load with a significant decrease in serum Mg concentration (within the normal range), while the IR group also exhibited a decline in tErMg and bErMg. The mean sum of insulin needed to metabolize the same glucose load correlated positively with tErMg (r=0.545, p<0.01) and bErMg (r=0.560, p<0.01) in the IR patients. It is concluded that, at an early stage of renal dysfunction, IR is not associated with the decline in free erythrocyte Mg concentration, but the magnesium handling in red blood cells is altered., K. Šebeková, K. Štefíková, D. Polakovičová, V. Spustová, R. Dzúrik., and Obsahuje bibliografii
It is well known that adrenalectomy (ADX) reverses the eating and energy balance disturbances in a variety of models of obesity associated with elevated food intake. We have previously demonstrated enhanced functional activity in the small intestine of neonatally monosodium glutamate-treated (MSG) obese rats despite the absence of overeating and we concluded that these changes might also contribute to the development of MSG obesity. The objective of the present experiments was to investigate whether ADX would affect the small intestinal functions and whether their changes would counteract attenuation or prevention of obesity development in MSG rats. Therefore the investigation was carried out in MSG-obese Wistar male rats and untreated intact rats adrenalectomized on day 40, as well as in lean littermates of MSG rats and intact rats subjected to Sham-ADX surgery. All animals had free access to a standard pellet diet after weaning. At the age of 80 days, body mass, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP), the dipeptidyl(amino)peptidase IV (DPP IV) and maltase activity were measured. During the postoperative period, ADX resulted in a significant decrease of mass gain in both MSG and control rats (P<0.05). ADX fully prevented the development of obesity in MSG rats (significantly decreased epididymal+retroperitoneal fat pad mass, P<0.05) and increased mean daily food intake (P<0.001). These effects were only minimal in the ADX controls suggesting that enhanced adrenal secretion is involved in the expression of MSG obesity and its complications. The AP activity in obese MSG rats was increased by about 21 % (P<0.01) in both intestinal segments when compared to the lean controls, whereas no parallel variations in the activities of DPP IV and maltase were observed in the intestinal parts mentioned. In MSG rats, ADX significantly reduced the AP activity in the duodenum and jejunum (P<0.01). A similar tendency was also seen in the DPP IV activity of adrenalectomized MSG rats as well as in lean control rats. Nevertheless, no significant effect of adrenal withdrawal on maltase activity was found. These results indicate that the decrease of enzyme activities in the small intestine and the different effectiveness of nutrient absorption might be a significant factor preventing the development of excess adiposity in glutamate-treated rats. This information contributes to a better understanding of the importance of small intestinal function for the development of obesity and its maintenance in later life.
We investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which has been found to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of three 12-week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions (P<0.01) in body weight and fat mass after the 12 week period in all groups: -11.4±0.5 kg and -9.8
±0.5 kg (OEWL), -8.3±0.8 kg and -5.7±0.9 kg (OWL), -8.9±1.2 kg and -7.4±1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2 %(OEWL1), -37.8 % (OWL) and -48.6 % (EWL) (P<0.01 all). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2
±7.2 % (OEWL), -27.8±4.8 % (OWL) and -39.3±4.3% (EWL) (P<0.01 all). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in the OEWL group compared to the OWL group (P=0.03). Consequently, an exercise training program in adjunct to
pharmacotherapy provides higher weight reduction and fat mass loss in obesity treatment. It also seems to have further beneficial effects on leptin re
sistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.
We examined the effects of weight loss induced by diet-orlistat (DO) and diet-orlistat combined with exercise (DOE) on maximal work rate production (Wmax) capacity in obese patients. Total of 24 obese patients were involved in this study. Twelve of them were subjected to DO therapy only and the remaining 12 patients participated in a regular aerobic exercise-training program in addition to DO therapy (DOE). Each patient performed two incremental ramp exercise tests up to exhaustion using an electromagnetically-braked cycle ergometer: one at the onset and one at the end of the 4th week. DOE therapy caused a significant decrease in total body weight: 101.5±17.4 kg (basal) vs 96.3±17.3 kg (4 wk) associated with a significant decrease in body fat mass: 45.0±10.5 kg (basal) vs 40.9±9.8 kg (4 wk). DO therapy also resulted in a significant decrease of total body weight 94.9±14.9 kg (basal) vs 91.6±13.5 kg (4 wk) associated with small but significant decreases in body fat mass: 37.7±5.6 kg (basal) to 36.0±6.2 kg (4 wk). Weight reduction achieved during DO therapy was not associated with increased Wmax capacity: 106±32 W (basal) vs 106±33 W (4 wk), while DOE therapy resulted in a markedly increased Wmax capacity: 109±39 W (basal) vs 138±30 W (4 wk). DO therapy combined with aerobic exercise training resulted in a significant reduction of fat mass tissue and markedly improved the aerobic fitness and Wmax capacities of obese patients. Considering this improvement within such a short period, physicians should consider applying an aerobic exercise-training program to sedentary obese patients for improving their physical fitness and thereby reduce the negative outcomes of obesity.
Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects. The vasodilator response to the ET-1 antagonist BQ123 (1 μM) was significantly higher in arteries from obese hypertensive patients (p<0.001). BQ123 induced relaxation was inhibited by NO synthase inhibitor L-NAME (0.1 nM). Preincubation with BQ123 enhanced the relaxation induced by acetylcholine (ACh; 0.1 nM - 0.1 mM) (p<0.001), but not that induced by NO donor sodium nitroprusside (SNP; 0.1 nM - 0.1 mM), in arteries from obese hypertensive patients. The present study show that hypertension yet prevail after gastric bypass surgery and the ETA receptor antagonist BQ123 may be a useful tool in reducing blood pressure in obese hypertensive patients., K. Gradin, B. Persson., and Seznam literatury
Body fat content is controlled, at least in part, by energy charge of adipocytes. In vitro studies indicated that lipogenesis as well as lipolysis depend on cellular ATP levels. Respiratory uncoupling may, through the depression of ATP synthesis, control lipid metabolism of adipose cells. Expression of some uncoupling proteins (UCP2 and UCP5) as well as other protonophoric transporters can be detected in the adipose tissue. Expression of other UCPs (UCP1 and UCP3) can be induced by pharmacological treat
ments that reduce adiposity. A negative correlation between the accumulation of fat and the expression of UCP2 in adipocytes was also found. Ectopic expression of UCP1 in the white fat of aP2-Ucp1 transgenic mice mitigated obesity induced by genetic or dietary factors. In these mice, changes in lipid metabolism of adipocytes were associated with the depression of intracellular energy charge. Recent data show that
AMP-activated protein kinase may be involved in the complex changes elicited by respiratory uncoupling in adipocytes. Changes in energy metabolism of adipose tissue may mediate effects of treatments directed against adiposity, dyslipidemia, and insulin resistance.