Renate Horejsi

Body fat distribution of overweight females with a history of weight cycling

Weight cycling may cause a redistribution of body fat to the upper body fat compartments. We investigated the distribution of subcutaneous adipose tissue (SAT) in 30 overweight women with a history of weight-cycling and age-matched controls (167 normal weight and 97 overweight subjects). Measurements of SAT were performed using an optical device, the Lipometer. The SAT topography describes the thicknesses of SAT layers at 15 anatomically well-defined body sites from neck to calf. The overweight women with a history of weight cycling had significantly thicker SAT layers on the upper body compared to the overweight controls, but even thinner SAT layers on their legs than the normal weight women. An android fat pattern was attributed to overweight females and, even more pronounced, to the weight cyclers. The majority of normal weight women showed a gynoid fat pattern. Using stepwise discriminant analysis, 89.0% of all weight cyclers and overweight controls could be classified correctly into the two groups. These findings show the importance of normal weight maintenance as a health-promoting factor.

Preatherosclerosis and Adiponectin Subfractions in Obese Adolescents

We evaluated total adiponectin, high‐molecular weight (HMW), medium‐molecular weight (MMW), low‐molecular weight (LMW) adiponectin subfractions, clinical parameters, routine lab parameters, lipids, metabolic, inflammatory biomarkers, and intima‐media thickness (IMT) of common carotid arteries in 70 obese juveniles and adolescents with preatherosclerosis and 55 normal weight controls of similar age and gender distribution. Compared with the controls, the obese probands had a significantly increased IMT (P < 0.001) and elevated ultra‐sensitive C‐reactive protein (P < 0.001) indicating early vascular burden. Total and HMW adiponectin were significantly decreased in the obese cohort. The ratio between HMW and total adiponectin was significantly decreased in obese probands whereas the LMW/total adiponectin ratio was increased. Overall, total‐, HMW, and MMW adiponectin were significantly negatively correlated with carotid IMT. The HMW/total adiponectin ratio correlated significantly negatively, and the LMW/total adiponectin ratio significantly positively with the IMT. Furthermore, HMW adiponectin was significantly positively correlated with high‐density lipoprotein (HDL)‐cholesterol and serum apolipoprotein A1, and negatively with BMI, triglycerides, homeostatic model assessment (HOMA)‐index, leptin, liver transaminases, and uric acid. This remained stable after controlling for gender. Multiple regression analysis of body measures and all other lab parameters showed the strongest correlation between HMW adiponectin and carotid IMT (β = −0.35, P < 0.001). Taken together, our study provides the first evidence that preatherosclerosis in obese juveniles and adolescents is associated with altered subfractions of adiponectin, whereas after multiple testing the HMW subfraction showed a better correlation to IMT compared with total adiponectin.

Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation

The mechanisms underlying the pathogenesis of obesity-related atherosclerosis remain to be clarified. To investigate the preclinical phase, interleukin-6 (IL-6) plasma levels were analyzed together with clinical, anthropometric, inflammatory, and metabolic variables in a well-defined cohort of 677 young and middle-aged overweight/obese and normal-weight subjects. In the juvenile and adult overweight/obese study group, IL-6 levels were increased significantly compared with normal-weight, age-matched controls (P < 0.001). In both juveniles and adults, higher levels of IL-6 were observed in obese compared with overweight participants. Subjects with metabolic syndrome (MS) had significantly higher IL-6 levels than those without MS. In juveniles, leptin, and in adults, the waist-to-height ratio, turned out to be the best predictor of IL-6 plasma levels in a multiple stepwise regression model. Taken together, in every age group, interleukin-6 is associated positively with the grade of overweight. Interestingly, leptin, which is the best known adipokine, is associated predictively with interleukin-6 plasma levels only in juveniles, which may indicate an important role of this molecule in the initiation of obesity-related inflammation.

Lipid profile in normal weight migraineurs – evidence for cardiovascular risk

Background:  Recent studies suggest that migraine is associated with metabolic disorders. In particular, migraine may be associated with cardiovascular risk; however, an association of migraine with cardiovascular risk factors like hypercholesterolemia has been proposed, but previous studies have yielded in part conflicting results. The aim of the present study is to evaluate the lipid profile in normal weight migraine patients.

Oxidative stress is associated with migraine and migraine-related metabolic risk in females.

Background and purpose:  Oxidative stress is discussed to be implicated in the pathophysiology of migraine. However, data are in part controversial and the possible underlying mechanisms remain elusive to date. The aim of this study was to investigate the oxidative stress status of female patients with migraine and its implications on migraine‐related metabolic alterations.

Increased nitric oxide stress is associated with migraine

Nitric oxide (NO) has been implicated in migraine attacks, but the role of NO in migraine remains unclear. We here hypothesize that increased NO in the headache-free period is associated with migraine. One hundred and thirty probands participated in this study. Various parameters of the NO pathway, such as nitrate, nitrite, arginine, citrulline, nitrosylated proteins, asymmetric dimethylarginine, symmetrical dimethylarginine, expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase and two polymorphisms of eNOS were investigated. We found significant increased nitrate and decreased nitrite levels in migraineurs in the headache-free period. Nitrate and nitrite levels showed a significant inverse correlation. Logistic regression revealed an odds ratio of 3.6 for migraine. Other parameters of the NO pathway were neither altered in migraineurs nor correlated with nitrate. We show here that migraine patients suffer under sustained increased nitrosative stress in the headache-free period, which is associated with a 3.6-fold higher risk for migraine.

Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles

Subcutaneous adipose tissue (SAT) topography contributes significantly to metabolic risk profiles and atherosclerotic vascular burden in obese adults. However, little information exists concerning individual risk profiles in early phases of obesity found in childhood and adolescence. Thus, the rationale of this study was to evaluate possible impacts of SAT topography in obese juveniles on adiponectin subfractions, with special emphasis on low molecular weight (LMW) adiponectin. To address this, we analysed associations between lipometry, early metabolic and preatherosclerotic symptoms and adiponectin subfractions in 71 obese juveniles and 75 normal weight controls of similar age and gender distribution. Compared to the controls, obese juveniles had a significantly decreased ratio between high molecular weight (HMW) and total adiponectin whereas the LMW/total adiponectin ratio was increased. The LMW/total adiponectin ratio correlated significantly positively with the SAT thickness of trunk-located lipometer measure points neck, biceps, upper back, lower back, body mass index (BMI), and waist circumference. Further significant positive correlations were seen with systolic blood pressure, intima media thickness (IMT) of common carotid arteries, and metabolic parameters such as HOMA-index, leptin, oxidized LDL (oxLDL), liver transaminases, and HDL-triglycerides. This remained stable after controlling for gender. A stepwise multiple regression analysis encompassing all these variables revealed a robust positive association between LMW/total adiponectin ratio and nuchal SAT thickness defined by the lipometer measure point neck. Taken together, our data provide the first evidence that nuchal SAT thickness is tightly positively associated with an increased LMW/total adiponectin ratio.

Increased matrix metalloproteinase activity is associated with migraine and migraine-related metabolic dysfunctions

Objective:  Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are discussed to be involved in the pathophysiology of migraine. Moreover, MMPs may also be involved in migraine‐related metabolic alterations like an atherogenic lipid profile and hyperinsulinemia. The aim of this study was to investigate the impact of MMPs and TIMPs on migraine with and without aura and related metabolic dysfunctions.

NADH stimulates endogenous dopamine biosynthesis by enhancing the recycling of tetrahydrobiopterin in rat phaeochromocytoma cells

Treatment of Parkinson patients with L-DOPA (3,4-dihydroxy-L-phenylalanine) leads to endproduct inhibition of tyrosine hydroxylase, the key enzyme in dopamine biosynthesis and the enzyme needing tetrahydrobiopterin and iron as cofactors. To overcome this problem an alternative treatment was investigated which attempted to stimulate endogenous dopamine biosynthesis. Incubation of rat PC 12 cells with NADH (beta-nicotinamide adeninedinucleotide) leads to increased dopamine production. We investigated the possibility that this increase of dopamine biosynthesis was due to stimulation of quinonoid dihydropteridine reductase, the enzyme which recycles the inactive dihydrobiopterin to the active tetrahydrobiopterin. The experiments showed that whereas NADH is able to increase dopamine production in PC 12 cells (rat phaeochromocytoma cells, clone PC 12) up to three-fold, no influence is exerted by NADH on pteridine metabolism; neither are tetrahydrobiopterin concentrations nor the de novo-biosynthesis of pteridines from guanosine triphosphate altered by NADH. Further no influence of NADH on protein de novo synthesis of quinonoid dihydropteridine reductase was observed. However, NADH was able to directly increase the catalytic activity of this enzyme. Our results suggest that the stimulation of dopamine biosynthesis by NADH is due to more rapid regeneration of quinonoid dihydrobiopterin to tetrahydrobiopterin.

Trunk weighted obesity, cholesterol levels and low grade inflammation are main determinants for enhanced thrombin generation

OBJECTIVE Endogenous thrombin generation (ETP) may be critically involved in obesity associated thromboembolism. METHODS Three hundred and one participants of the STyrian Juvenile OBesity (STYJOBS)/Early DEteCTion of Atherosclerosis (EDECTA) study cohort (age, 16-58years) were analysed. ETP was measured by the new CE-IVD marked Siemens-Innovance(®) ETP test on a BCS-XP analyser, and correlated to clinical findings and extended lipometry-based anthropometric data, biomarkers, and coagulation parameters. RESULTS In the overweight/obese study group, ETP and fibrinogen levels were significantly higher compared to controls (p<0.001). In a multiple stepwise regression including all subjects, subcutaneous adipose tissue thickness of upper back, cholesterol and ultrasensitive C-reactive protein were the best predictors for ETP. CONCLUSION Trunk weighted obesity together with low grade inflammation and hypercholesterolemia enhance thrombin generation.