期刊
KIDNEY INTERNATIONAL
卷 98, 期 3, 页码 663-672出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2020.03.027
关键词
browning; cardiac natriuretic peptides; chronic kidney disease; protein energy wasting
资金
- Fondation du Rein (Prix Jeune Chercheur 2016)
- Hospices Civils de Lyon, INSERM (Institut National de la Sante et de la Recherche Medicale)
- INSALyon (Institut National des Sciences Appliquees de Lyon)
- grant-Annee Recherche-from Hospices Civils de Lyon
- Agence Regionale de Sante (ARS)
- Fondation Recherche Medicale
Protein energy wasting is a common feature of patients with chronic kidney disease (CKD) and is associated with poor outcomes. Protein energy wasting and cachexia, a severe form of protein energy wasting, are characterized by increased resting energy expenditure but the underlying mechanisms are unclear. Browning corresponds to the activation of inducible brown adipocytes in white adipose tissue and occurs in states of cachexia associated with hypermetabolic disease such as cancer. Here we tested the hypothesis that CKD-associated protein energy wasting could result from browning activation as a direct effect of the uremic environment on adipocytes. In a murine model of CKD (5/6 nephrectomy), there was increased resting energy expenditure, expression of uncoupling protein 1 (a thermogenic protein uncoupling oxidative phosphorylation in mitochondria) and citrate synthase activity (a proxy of mitochondria) density in white adipose tissue). Mice with CKD also exhibited increased levels of atrial natriuretic peptide, a well known activator of browning. The incubation of primary adipose cells with plasma from patients receiving dialysis treatment and having signs of protein energy wasting led to an increased synthesis of uncoupling protein 1. Similarly, primary adipose cells exposed to atrial natriuretic peptide at concentrations relevant of CKD led to a significant increase of uncoupling protein 1 content. Thus, accumulation of cardiac natriuretic peptides during CKD could contribute the browning of white adipose tissue and protein energy wasting.
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