Basal and exercise-induced sympathetic nervous activity and lipolysis in adipose tissue of patients with anorexia nervosa

BACKGROUND: The sympathetic nervous system plays an important role in the regulation of adipose tissue (AT) lipolysis, which is a key step in the metabolic processes leading to the decrease of fat mass. The present study was designed to determine in vivo basal and exercise-stimulated lipolysis and concentrations of catecholamines, the major hormones controlling lipolysis, in subcutaneous abdominal AT in patients with anorexia nervosa (AN), characterized by self-induced starvation and excessive exercises resulting in severe malnutrition and fat store loss. The results of local catecholamines and glycerol levels were compared with those in plasma in both experimental groups. MATERIAL AND METHODS: An in vivo microdialysis technique was used for the assessment of norepinephrine, dihydroxyphenylalanine, dihydroxyphenylacetic acid and glycerol concentrations in subcutaneous AT of 10 women with AN (body mass index: 15.57 +/- 0.55 kg m(-2)) and 10 age-matched controls (body mass index: 21.56 +/- 0.41 kg m(-2)). Both the AN patients and the control subjects underwent a 1.5 W kg(-1) exercise test. RESULTS: Basal AT norepinephrine concentrations were increased in the AN patients in comparison with the controls. Basal AT glycerol concentrations were similar in both groups. During exercise, a local increase in the AT norepinephrine and glycerol concentrations was observed in the AN patients only. In contrast to the controls, the basal AT dihydroxyphenylalanine and dihydroxyphenylacetic acid levels in the AN patients were high and remained unchanged during exercise. Basal and exercise-stimulated plasma norepinephrine, dihydroxyphenylalanine, dihydroxyphenylacetic acid and glycerol levels were not different in the AN patients and healthy controls. CONCLUSION: Our study provides evidence of elevated baseline and exercise-induced sympathetic nervous activity and exercise-induced lipolysis in abdominal AT of AN patients.     

Effects of nicotinic acid treatment on glyceride formation and lipolysis in adipose tissue of hyperlipidemic patients

Summary Thirty-one weight-stable patients with different types of hyperlipoproteinemia were treated daily with 4g nicotinic acid for 6 weeks. Effects of this therapy on adipose tissue metabolism were evaluated. By using biopsy specimens of subcutaneous adipose tissue, fatty acid and glucose incorporation into adipose tissue glycerides were measured in vitro as well as glycerol and fatty acid release, which allowed us to estimate adipose tissue lipolysis. The amount of fatty acids produced by lipolysis and thereafter utilized within adipose tissue without being released (fatty acid retention) was estimated. Fatty acid and glucose incorporation into adipose tissue, glycerol release and fatty acid retention values increased, but serum triglyceride levels decreased (allP<0.001) after nicotinic acid treatment. The change in fatty acid incorporation was positively correlated with changes in glucose incorporation into adipose tissue (r=0.53,P<0.01) and fatty acid retention (r=0.76,P<0.001). Although adipose tissue lipolysis, measured as glycerol release, increased, the lipolyzed fatty acids were retained in adipose tissue, suggesting an enhanced synthesis of glycerides both from exogenous and endogenous sources. The increase in fatty acid incorporation into adipose tissue indicates that the decrease in serum triglyceride levels produced by nicotinic acid treatment may partly be due to the fact that this drug promotes incorporation of fatty acids, derived from lipoprotein-carried triglycerides in the blood, into adipose tissue glycerides.     

Plasma factor VII and its relation to adipose tissue fatty acids and other atherogenic risk factors in healthy men

In this study the authors examined the relationships of plasma factor VII (F–VII) to adipose tissue fatty acid composition, as an objective index of the habitual dietary fat intake, as well as to a number of other atherogenic risk factors in 60 healthy male volunteers (aged 38 years). Significant positive correlations were found between plasma F-VII [measured as antigen (F-VIIAg) and coagulant activity, using bovine thromboplastin (F-VIIbt)] and body mass index (BMI), waist–thigh girth ratio (WTR), cigarette smoking and plasma triglyceride concentration. After adjustment for BMI, only plasma triglycerides remained positively correlated with F-VII (r = 0.27, P = 0.03, and r = 0.29, P < 0.01, for F-VIIbt and F-VIIAg respectively). A significant positive relation was found between F-VII and the total proportion of fatty acid as monounsaturated fatty acid (r = 0.26, P < 0.05, for F-VIIAg), whereas inverse relations were found between F-VII, the total proportion of fatty acid as polyunsaturated fatty acid (r = ? 0.26 and r = ? 0.25, P < 0.05, for F-VIIbt and F-VIIAg respectively), polyunsaturated–saturated fat ratio (r = ? 0.25, P < 0.05, for F-VIIbt) and, more significantly, between F-VII and adipose-tissue α-linolenic acid (r = ? 0.29, P < 0.01, for F-VIIbt and r = ? 0.49, P < 0.001, for F-VIIAg). All these correlations remained significant after matching for BMI. In a multiple linear regression analysis, only adipose tissue α-linolenic acid was a negative and independent predictor of F-VIIAg (P = 0.004) and, at borderline significance, of F-VIIbt (P = 0.061) when allowance was made for BMI, WTR, smoking and plasma triglycerides. In conclusion, this study shows significant relations between F-VII and adipose tissue fatty acid composition in healthy male individuals; it supports the possibility that adipose tissue poly- unsaturated fatty acids, derived from dietary intake, play a role in the relation between F-VII and coronary heart disease (CHD), thus suggesting that high dietary polyunsaturated fatty acid intake (especially α-linolenic acid) may reduce the risk for CHD by an improvement of a number of risk factors, including a lowering of plasma F-VII (both activity and antigen).     

Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels

The associations of adipose tissue lipoprotien lipase (AT-LPL) activity with body fatness and plasma lipoprotein levels were studied in the light of the recently described regional differences in AT-LPL activity. In this regard, heparin-releasable LPL activity was measured in abdominal and femoral adipose tissues of 29 pre-menopausal women. Body fatness variables were all positively correlated with abdominal and femoral AT-LPL activities expressed per 10(6) cells. However, abdominal and femoral AT-LPL activities expressed per unit of cell surface displayed divergent association patterns with body fatness and plasma lipoprotein levels. Indeed, only abdominal AT-LPL activity remained significantly correlated with body fatness variables after adjustment for fat cell surface. Furthermore, whereas abdominal AT-LPL activity tended to be negatively correlated with plasma HDL-cholesterol levels, femoral AT-LPL activity was positively correlated with plasma HDL2-cholesterol (r = 0.40, P less than 0.05) concentration and with the HDL2-cholesterol/HDL3-cholesterol ratio (r = 0.49, P less than 0.01). These results demonstrate the importance of taking into account the regional variation in metabolic activity of adipose tissue when studying its associations with body fatness, and with plasma lipoprotein levels. The lack of association between abdominal AT-LPL activity and plasma HDL2-cholesterol levels lead us to suggest that AT-LPL activity may not be causally related with plasma HDL levels.     

Plasma fibrinogen in relation to serum insulin, smoking habits and adipose tissue fatty acids in healthy men

Abstract. Recent prospective studies have reported an independent association between fibrinogen plasma levels and risk of cardiovascular events. Aim of this study was to investigate the relationships between fibrinogen level and conventional cardiovascular risk factors in a random sample of 38 year-old apparently healthy men ( n = 94), and to verify whether the fatty acid composition of the diet might influence those relations. Anthropometric measurements, serum lipids, blood pressure, and smoking habits were evaluated. In addition, fasting and after glucose-load serum glucose and insulin concentrations were measured. The most significant difference in fibrinogen level was found among the tertiles of fasting serum insulin (F anova = 4·5; P < 0·01) with the highest plasma fibrinogen values in the third insulin tertile, whereas body mass index (BMI), waist/hip circumference ratio (WHR) and serum triglycerides were more weakly related. The current smokers had substantially higher levels of fibrinogen than subjects who never smoked ( P < 0·001). A multivariate regression analysis showed that, among the above reported variables, only serum insulin and smoking were independently associated with plasma fibrinogen. Furthermore, as the possible association between fatty acid composition of the diet and fibrinogen level regards, we have examined the fatty acid composition of adipose tissue, as a good and objective index of quality of the dietary fat intake. It was found that, fibrinogen level was not associated with any adipose tissue fatty acid. In conclusion, this study performed in a random sample of healthy men indicates an independent relationship of fasting insulin and smoking to fibrinogen plasma level.     

高频超声测量心外膜脂肪组织厚度与冠心病危险因素的相关性分析

目的 采用高频超声技术探讨冠心病患者心外膜脂肪(EAT)厚度与冠心病危险因素的相关性.方法 84例患者根据冠脉造影结果分为冠脉正常组(28例)、冠心病单支病变组(28例)、冠心病多支病变组(28例),用高频超声分别测量EAT厚度和颈动脉IMT,将EAT厚度与颈动脉IMT等冠心病危险因素进行相关性分析.结果 冠心病单支病...     

Identification of oestrogen receptors and oestrogen receptor mRNA in human adipose tissue

The distribution of adipose tissue has a major impact on the morbidity and mortality associated with obesity. Furthermore, the distribution of adipose tissue seems to be regulated by sex hormones. Controversy exists over whether the effects of sex hormones (oestrogen and testosterone) on human adipose tissue are an indirect or a direct effect as contradictory results have been obtained when investigating the existence of these receptors in human adipose tissue. In the present study the authors reinvestigated the possible existence of oestrogen receptors (ERs) in human adipose tissue. Human adipocytes from both genders were found to contain specific oestrogen binding sites determined by ligand-binding techniques. The binding protein had a molecular weight of 65 kD (which is similar to that of the ER found elsewhere) and it was found that adipocytes contained mRNA encoding the ER. Moreover, human preadipocytes had no oestrogen-binding capacity and did not possess mRNA encoding the ER. Finally, the authors detected regional differences in receptor density. Women had an equal oestrogen-binding capacity in adipose tissue from the subcutaneous abdominal and the visceral depot, whereas men had twice as high oestrogen-binding capacity in subcutaneous adipose tissue compared with adipose tissue in the visceral fat depot. These findings indicate that mature human adipocytes possess ERs and thus, might be an oestrogen- responsive tissue and that oestrogen may be acting directly in mature adipocytes via its specific receptor. Human preadipocytes, however, seemed not to be an oestrogen-responsive tissue. Finally, preliminary data suggest that there might be differences in ER densities in different fat depots.     

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study

The associations between fasting plasma insulin concentration and risk factors for cardiovascular diseases were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)–total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles (F =7.1; P <0.001). However, systolic blood pressure and uric acid were close to statistical significance (P =0.06–0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e. three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables (F =4.0; P <0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.     

Relationship between fasting insulin and cardiovascular risk factors is already present in young men: the Verona Young Men Atherosclerosis Risk Factors Study

The associations between fasting plasma insulin concentration and risk factors for cardiovascular diseases were examined in 979 18-year-old men participating in the Verona Young Men Atherosclerosis Risk Factors Study, a cross-sectional population-based study. Body mass index (BMI), waist-to-hip ratio (WHR), plasma triglycerides and uric acid concentrations, and blood pressure values significantly increased, and the high-density lipoprotein (HDL)–total cholesterol ratio decreased, across quartiles of fasting insulin. Total and low-density lipoprotein cholesterol concentrations did not change significantly with the increase in fasting insulin levels. After adjustment for BMI, WHR, smoking, alcohol intake and physical activity, only plasma triglycerides significantly increased across insulin quartiles ( F  =7.1; P  <0.001). However, systolic blood pressure and uric acid were close to statistical significance ( P  =0.06–0.07). Multiple linear regression analysis confirmed that plasma insulin was independently correlated with plasma triglycerides and, to a lesser extent, with blood pressure and uric acid concentration. This analysis pointed out that BMI was a stronger independent predictor of all cardiovascular disease risk factors than fasting insulin. When subjects were categorized according to the number of metabolic and haemodynamic disorders occurring within the same individual, subjects with multiple disorders (i.e. three or four) had higher plasma insulin levels than those with none or few disorders, even after adjusting for BMI, WHR and behavioural variables ( F  =4.0; P  <0.01). These results indicate that hyperinsulinaemia is already associated with a cluster of cardiovascular disease risk factors in young adulthood, the strongest independent association being with plasma triglycerides.     

Differences in Lipolysis between Human Subcutaneous and Omental Adipose Tissues

Hydrolysis of triglycerides to fatty acids and glycerol in fat cells (lipolysis) is of importance for the control of lipid and carbohydrate metabolism. This process is regulated by several hormones and parahormones acting on cyclic AMP formation or breakdown, which in turn influences the activity of hormone sensitive lipase. The latter enzyme stimulates hydrolysis of triglycerides in fat cells. It is well established through in vivo and in vitro investigations that there are regional variations in the lipolytic activity of human adipose tissue. The rate of lipolysis is low in the subcutaneous femoral/gluteal region, intermediate in the subcutaneous abdominal region and high in the visceral (i.e. omental) region. In non-obese subjects the differences between the subcutaneous and visceral fat depots may be explained by site variations in the function of receptors for insulin, catecholamines and adenosine. The lipolytic beta₁ and beta₂ adrenoceptors, as well as the newly discovered beta₃, are most active in the visceral fat cells. The antilipolytic insulin receptors, alpha₂ adrenoceptors and adenosine receptors are most active in the subcutaneous fat cells. In subjects with upper-body obesity the regional variations in the action of catecholamines on lipolysis are further enhanced. Decreased action of beta₂-adrenergic receptors and increased activity of alpha₂-adrenergic adrenoceptors in combination with defects in hormone sensitive lipase function inhibits the lipolytic effect of catecholamines in subcutaneous fat cells whereas increased activity of beta₃-adrenergic receptors and decreased activity of alpha₂ adrenoceptors augment the lipolytic response in visceral fat cells. These abnormalities in catecholamine function promote release of free fatty acids from the visceral fat cells to the liver through the portal system and might cause several of the metabolic complications to upper-body obesity.     

Visfatin expression in subcutaneous adipose tissue of pre-menopausal women: relation to hormones and weight reduction

Background A novel adipokine, visfatin, was found to be related to adiposity in humans and regulated by a number of hormonal signals. The aim of this study was to investigate the relationships of visfatin expression in adipose tissue with potential regulatory factors such as insulin, testosterone and tumor necrosis factor‐α (TNF‐α) and to elucidate the effect of a diet induced weight reduction on adipose tissue mRNA expression and plasma levels of visfatin. Materials and methods Biopsies of subcutaneous abdominal adipose tissue (SCAAT) and plasma samples were obtained at the beginning of the study from 47 pre‐menopausal women (age 38·7 ± 1·7 years, body mass index (BMI) 27·9 ± 1·4 kg m^?2), consisting of 15 lean, 16 overweight and 16 obese subjects. The subgroup of 32 overweight/obese women (age 42·1 ± 1·9 years, BMI 31·2 ± 0·9 kg m^?2) underwent a 12 week hypocaloric weight reducing diet and samples were obtained at the end of the diet. Biopsy samples were analysed for visfatin and TNF‐α mRNA levels and plasma was analysed for relevant metabolites and hormones. Results In the group of 47 subjects visfatin mRNA expression in SCAAT was negatively correlated with plasma free testosterone (r = –0. 363, P < 0·05) and BMI (r = –0·558, P < 0·01) and positively associated with adipose tissue TNF‐α mRNA expression (r = 0·688, P < 0·01). The diet resulted in the reduction of body weight and in the decrease of plasma insulin, free testosterone and TNF‐α levels. In the group of overweight/obese subjects visfatin mRNA in SCAAT increased after the diet and the diet induced increase was positively correlated with the magnitude of body weight loss. Conclusion Visfatin mRNA expression in SCAAT is associated with TNF‐α expression, plasma free testosterone and BMI in pre‐menopausal women. A weight reducing hypocaloric diet results in the increase of visfatin mRNA in SCAAT.     

高频超声测量心外膜脂肪组织厚度与冠心病危险因素的相关性分析

Objective To explore the correlation between epicardial adipose tissue(EAT) thickness and cardiovascular risk factors in patients with coronary artery disease.Methods According to the results of coronary angiography,84 cases of patients undergone coronary angiography were divided into the normal control group(28 patients),coronary artery disease group with single-vessel lesion (28 patients),coronary artery disease group with multi-vessels lesion(28 patients),respectively,then measured the EAT thickness and carotid intima-media thickness(IMT) by high-frequency ultrasound.A correlation analysis was carried out between the EAT and IMT and cardiovascular risk factors.Results In either coronary artery disease group with single-vessel lesion or multi-vessels lesion,the thicknesses of EAT and IMT were significantly higher than those in the normal control group(P ＜0.01),and the difference between group of single-vessel lesion and multi-vessels lesion was also statistically significant (P ＜0.01).A correlation analysis between the EAT and IMT and cardiovascular risk factors showed that there were significantly positive correlations between EAT and the IMT,age,weight,waist circumference,body mass index,low-density lipoprotein,Creactive protein (r = 0.124～0.790,P ＜0.05 or P ＜0.01),and the significantly negative correlation between EAT and high-density lipoprotein (r = - 0.203,P ＜ 0.05).Correlation between EAT and the IMT was 0.678,0.713,0.737 in the normal control group,group with single-vessel lesion,group with multivessels lesion,respectively.Conclusions There were favorable correlation between EAT and carotid IMT in cardiovascular risk factors.The more severity of coronary heart disease,the more high correlations of EAT and IMT.EAT can be a valuable index in evaluating coronary artery disease.     

Comparison of infrapatellar and subcutaneous adipose tissue stromal vascular fraction and stromal/stem cells in osteoarthritic subjects

Since inflammatory mechanisms have been postulated to link obesity to osteoarthritis, the current study evaluated the ratio of immune cells to multipotent stromal cells within the infrapatellar fat pad (IPFP) and subcutaneous adipose tissue (SQ) of the knee; each depot has potential as a source of regenerative cells. The immunophenotypes of stromal vascular fraction (SVF) and adipose‐derived stem cells (ASCs) of the IPFP and SQ were determined in tissues from osteoarthritic subjects (n = 7) undergoing total knee replacement. Based on a subset of surface antigens, the immunophenotype of ASCs from SQ of OA subjects was not significantly different from that of relatively healthy and leaner subjects undergoing elective liposuction surgery. Flow‐cytometry comparison of SVF cell populations in the IPFP of OA subjects resembled those within the subject's own matched SQ, with the exception of the endothelial marker CD31⁺, which was significantly greater in cells from SQ. In the OA subjects, lower numbers of capillary‐like structures and higher numbers of stromal and alkaline phosphatase colony‐forming units in the IPFP vs SQ were consistent with this finding; however, ASCs from both depots in OA subjects exhibited comparable adipogenic and osteogenic differentiation potential. Thus, the IPFP contains an ASC and immune cell population similar to that of donor‐matched SQ, making it an alternative ASC source for tissue regeneration. Further studies will be needed to determine whether IPFP immune cell infiltrates play an aetiological role in osteoarthritis equivalent to that shown in diabetes associated with obesity. Copyright © 2012 John Wiley & Sons, Ltd.     

The plasma kallikrein–kinin system and risk of cardiovascular disease in men

BACKGROUND: The plasma kallikrein-kinin system (PKKS) has been implicated in cardiovascular disease, but activation of the PKKS has not been directly probed in individuals at risk of coronary heart disease (CHD) or stroke. OBJECTIVE: To determine the involvement of the PKKS, including factor XI, in cardiovascular disease occurring in a nested case-control study from the Second Northwick Park Heart Study (NPHS-II). METHODS AND RESULTS: After a median follow-up of 10.7 years, 287 cases of CHD and stroke had been recorded and 542 age-matched controls were selected. When FXIIa-C1 esterase inhibitor (C1-inhibitor) concentrations were divided into tertiles (lowest tertile as reference), the odds ratios (ORs) at 95% CIs for CHD were 0.52 (0.34-0.80) in the middle tertile and 0.73 (0.49-1.09) in the highest tertile (P = 0.01 for the overall difference; P = 0.01 for CHD and stroke combined). For kallikrein-C1-inhibitor complexes, the ORs for stroke were 0.29 (0.12-0.72) and 0.67 (0.30-1.52) in the middle and high tertiles, respectively (P = 0.02). FXIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes were negatively related to smoking and fibrinogen (P < 0.005). FXIa-inhibitor complexes correlated strongly with FXIIa-inhibitor complexes. CONCLUSIONS: Lower levels of inhibitory complexes of the PKKS enzymes and particularly of FXIIa contribute to the risk of CHD and stroke in middle-aged men. This observation supports the involvement of the PKKS in atherothrombosis.     

Lipoprotein lipase activity in muscle tissue influenced by fatness, fat distribution and insulin in obese females

Abstract. Obesity is associated with dyslipidaemia and increased morbidity and mortality from premature atherosclerosis and diabetes mellitus. Particularly, hypertriglyceridaemia is a characteristic finding in patients with obesity. In addition, the elevated levels of triglycerides may be an important risk factor for development of the obesity-related complications. Lipoprotein lipase activity in skeletal muscle tissue (mLPL) has previously been found to be an important factor regulating the concentration of serum triglycerides. To describe the relationship between mLPL, triglycerides and fatness/fat distribution in more detail we have investigated these parameters under basal conditions and during insulin stimulation in 20 obese females. During hyperinsulinaemia (204 μU ml^-1) for 4 h the mLPL activity decreased from 528 ± 52 nmol FFA g^-1 to 412 ± 44 (P< 0.001). Basal mLPL was negatively correlated with serum triglycerides (r= -0.48, P<0.05) and positively correlated with HDL-cholesterol (r = 0–58, P<0.01). Employing multiple variance analysis it was found that both BMI and WHR were negatively correlated to mLPL, however, the impaired lipid profile (high triglyceride, low HDL-cholesterol, high FFA) could only be related to BMI and not to WHR in these obese females. However, reduced insulin-action (insulin resistance) was closely related to abdominal fatness determined by WHR both in relation to the insulin-effect on mLPL as well as for the insulin-effect on whole-body glucose metabolism (clamp-study). A tendency to a positive correlation was observed between the impaired insulin-stimulated glucose disposal and the reduced insulin-effect on mLPL (r = 0.41, P = 0.08) indicating that mLPL might be an indicator of muscle insulin sensitivity. In conclusion, reduced mLPL activity seems to play a role for the increased triglyceride levels associated with obesity and the mLPL activity seems to be negatively influenced by both total fatness and abdominal fatness. Finally, mLPL is an insulin sensitive enzyme where short-term insulin infusion inhibits the enzyme activity.     

Cholesterol and DNA content in arterial tissue in severe obesity: their relation to some risk factors for ischaemic heart disease

Arterial tissue was obtained from twelve severely obese patients during jejuno-ileal by-pass surgery. The arterial DNA content was inversely correlated with the sum of venous glucose values during an oral glucose tolerance test (rs = -0.72). This observation may have implications on the known relationship between decreased glucose tolerance and early manifestations of atherosclerosis.