Search

Abstract: Objective: The study of small-molecule metabolites may assist in cardiovascular risk monitoring during therapy. We assessed whether acute changes in the metabolome by lipoprotein apheresis are able to predict changes in microvascular function. Methods: We performed mass-spectrometry-based profiling of 186 metabolites in peripheral plasma of 21 hyperlipidemic patients before and after a single session of lipoprotein apheresis. To evaluate the capability of metabolites to predict microvascular outcome after apheresis, patients were stratified according to improvement and deterioration of retinal endothelial function. Endothelial function was assessed as the relative change in retinal vessel diameter in response to flicker light stimulation. Results: We observed pronounced but not uniform changes in the metabolome after a single session of lipoprotein apheresis. Improvements in microvascular function were associated with a decline in lysophosphatidylcholines C14:0, C16:0, C16:1, C18:0, C18:1, C18:2, C20:4, C28:0, C28:1; in the amino acid serine and the dicarboxyacylcarnitine C12-DC. A positive relationship was found for methionine and ornithine. Applying decision tree and receiver–operator characteristic curve analysis, a change in serine of smaller than 11% by lipoprotein apheresis predicted an improvement of microvascular function with high sensitivity. Conclusion: Lipoprotein apheresis elicits changes in the metabolome favoring an anti-atherosclerotic environment. Monitoring the serine profile may assist in risk management of patients undergoing regular lipoprotein apheresis. [Copyright &y& Elsevier]

Background/objectives:Obesity is a major risk factor for the development of type 2 diabetes and other debilitating diseases. Obesity and diabetes are intimately linked with altered levels of adrenal steroids. Elevated levels of these hormones induce insulin resistance and cause cardiovascular diseases. The mechanisms underlying obesity-related alterations in adrenal steroids are still not well understood. Here, we investigated how diet-induced obesity affects the morphology and function of the mouse adrenal cortex.Methods:We fed animals either a high-fat diet (HFD) or a normal diet (60% kcal from fat or 10% kcal from fat, respectively) for 18 weeks. We then assessed various aspects of adrenal gland morphology and function, as well as basal plasma concentrations of steroid hormones and ACTH.Results:We show that adrenal glands of mice fed a HFD release more corticosterone and aldosterone, resulting in higher plasma levels. This increase is driven by adrenal cortical hyperplasia, and by increased expression of multiple genes involved in steroidogenesis. We demonstrate that diet-induced obesity elevates Sonic hedgehog signaling in Gli1-positive progenitors, which populate the adrenal capsule and give rise to the steroidogenic cells of the adrenal cortex. Feeding animals with a HFD depletes Gli1-positive progenitors, as the adrenal cortex expands.Conclusions:This work provides insight into how diet-induced obesity changes the biology of the adrenal gland. The association of these changes with increased Shh signaling suggests possible therapeutic strategies for obesity-related steroid hormone dysfunction. [ABSTRACT FROM AUTHOR]