Josef R. Patsch

Bio: Josef R. Patsch is an academic researcher from Innsbruck Medical University. The author has contributed to research in topics: Cholesterol & Reverse cholesterol transport. The author has an hindex of 37, co-authored 107 publications receiving 3728 citations.

Relationship of the Plasma Levels of This Lipoprotein Species to Its Composition, to the Magnitude of Postprandial Lipemia, and to the Activities of Lipoprotein Lipase and Hepatic Lipase

Abstract: Lipoprotein lipase (LPL) activity in postheparin plasma of 38 normolipidemic volunteers was related to the magnitude of postprandial lipemia after a fat meal, to triglyceride content of high density lipoprotein2 (HDL2), to hepatic lipase (HL) activity, and to HDL2 levels. LPL activity correlated indirectly with lipemia, triglyceride content of HDL2, HL activity, and levels of HDL2 but not of HDL3. HL activity correlated directly with lipemia and indirectly with HDL2 levels. Triglyceride content of HDL2 correlated directly with lipemia and indirectly with HDL2 levels. In HDL2, abundance of apolipoprotein (apo) A-II and the apoA-I/apoA-II ratio varied widely. The latter correlated positively with LPL activity and HDL2 levels, and, inversely, with HL activity, lipemia, and triglyceride content of HDL2. The study suggests that HDL-cholesterol is not an independent parameter of lipid transport, but is strongly affected by triglyceride metabolism through lipolytic enzymes, as exemplified by postprandial lipemia that affect both composition and plasma levels of HDL2.

A Functional Polymorphism in the Promoter of UCP2 Enhances Obesity Risk but Reduces Type 2 Diabetes Risk in Obese Middle-Aged Humans

Abstract: Obesity is frequently associated with type 2 diabetes. We previously observed an association of a functional G/A polymorphism in the uncoupling protein 2 (UCP2) promoter with obesity. The wild-type G allele was associated with reduced adipose tissue mRNA expression in vivo , reduced transcriptional activity in vitro, and increased risk of obesity. On the other hand, studies in animal and cell culture models identified pancreatic β-cell UCP2 expression as a main determinant of the insulin secretory response to glucose. We therefore ascertained associations of the −866G/A polymorphism with β-cell function and diabetes risk in obesity. We show here that the pancreatic transcription factor PAX6 preferentially binds to and more effectively trans activates the variant than the wild-type UCP2 promoter allele in the β-cell line INS1-E. By studying 39 obese nondiabetic humans, we observed genotype differences in β-cell function; wild-type subjects displayed a greater disposition index (the product of insulin sensitivity and acute insulin response to glucose) than subjects with the variant allele ( P < 0.03). By comparing obese subjects with and without type 2 diabetes, we observed genotype-associated differences in diabetes prevalence that translated into a twofold age-adjusted risk reduction in wild-type subjects. Thus, the more common UCP2 promoter G allele, while being conducive for obesity, affords relative protection against type 2 diabetes.

Postprandial state and atherosclerosis.

Abstract: Accumulating evidence suggests that triglyceride-rich lipoproteins are an independent risk factor for atherosclerosis. This epidemiological evidence first emerged as a result of studying postprandial lipaemia that characterized the metabolic capacity of triglycerides in the postabsorptive state, tha

Peripheral infusion of rat bone marrow derived endothelial progenitor cells leads to homing in acute lung injury

Abstract: Bone marrow-derived progenitors for both epithelial and endothelial cells have been observed in the lung. Besides mature endothelial cells (EC) that compose the adult vasculature, endothelial progenitor cells (EPC) are supposed to be released from the bone marrow into the peripheral blood after stimulation by distinct inflammatory injuries. Homing of ex vivo generated bone marrow-derived EPC into the injured lung has not been investigated so far. We therefore tested the hypothesis whether homing of EPC in damaged lung tissue occurs after intravenous administration. Ex vivo generated, characterized and cultivated rat bone marrow-derived EPC were investigated for proliferation and vasculogenic properties in vitro. EPC were tested for their homing in a left-sided rat lung transplant model mimicking a severe acute lung injury. EPC were transplanted into the host animal by peripheral administration into the femoral vein (106 cells). Rats were sacrificed 1, 4 or 9 days after lung transplantation and homing of EPC was evaluated by fluorescence microscopy. EPC were tested further for their involvement in vasculogenesis processes occurring in subcutaneously applied Matrigel in transplanted animals. We demonstrate the integration of intravenously injected EPC into the tissue of the transplanted left lung suffering from acute lung injury. EPC were localized in vessel walls as well as in destructed lung tissue. Virtually no cells were found in the right lung or in other organs. However, few EPC were found in subcutaneous Matrigel in transplanted rats. Transplanted EPC may play an important role in reestablishing the endothelial integrity in vessels after severe injury or at inflamatory sites and might further contribute to vascular repair or wound healing processes in severely damaged tissue. Therapeutic applications of EPC transplantation may ensue.

Effect of mirtazapine treatment on body composition and metabolism.

Abstract: Objective Weight gain is a common side effect of psychotropic medications. Mirtazapine, a widely used antidepressant, induces adverse metabolic effects such as an increase in body weight. The aim of this study was to investigate the influence of mirtazapine treatment on body weight, body fat mass, glucose metabolism, lipoprotein profile, and leptin and its soluble receptor in a prospective, controlled study design. Method Seven women who met the ICD-10 diagnostic criteria for a depressive episode (ICD-10: F31-F33) were assigned to monotherapy with mirtazapine and observed for a 6-week period. Seven mentally and physically healthy female volunteers matched for age and body weight served as a control group. Data were collected from November 2002 to December 2003. Results The mean +/- SD body weight increased from 63.6 +/- 13.1 kg to 66.6 +/- 11.9 kg during mirtazapine treatment (p = .027). Fat mass increased in study subjects from 20.9 +/- 9.6 kg to 22.1 +/- 9.3 kg (p = .018). Insulin, glucose, and the homeostasis model assessment (HOMA) index for insulin resistance and lipid parameters remained stable. Leptin concentrations increased from 23.0 +/- 17.1 ng/mL to 40.9 +/- 27.2 ng/mL (p = .018), whereas the soluble leptin receptor concentrations remained stable during mirtazapine treatment. In the control subjects, the investigated parameters remained stable. Between-group analyses of change scores revealed significant differences for body weight (p = .010), body mass index (p = .013), fat mass (p = .035), and leptin (p = .013). Conclusion The antidepressant therapy with mirtazapine was associated with a significant increase in body weight, body fat mass, and leptin concentration. In contrast to other psychotropic medications inducing weight gain, such as some second-generation antipsychotics, mirtazapine treatment did not influence the glucose homeostasis.

Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein E

Abstract: Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process

Mitochondrial dysfunction and type 2 diabetes.

Abstract: Maintenance of normal blood glucose levels depends on a complex interplay between the insulin responsiveness of skeletal muscle and liver and glucose-stimulated insulin secretion by pancreatic β cells. Defects in the former are responsible for insulin resistance, and defects in the latter are responsible for progression to hyperglycemia. Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction.