Abstract: TH-PO414

Activation of Browning in White Adipose Tissue during CKD

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism


  • Luce, Mathilde, Hospices Civils of Lyon, Lyon, France
  • Elsa, Nyam, Montreal Diabetes Research Center, CRCHUM and Department of Medicine, University of Montréal,, Montréal, Quebec, Canada
  • Soulage, Christophe O., CarMeN, INSERM u1060, INSA LYON, VILLEURBANNE, France
  • Fouque, Denis, Hospices Civils of Lyon, Lyon, France
  • Koppe, Laetitia, Hospices Civils of Lyon, Lyon, France

In patients with chronic kidney disease (CKD), protein energy wasting (PEW) is characterized by an increased resting energy expenditure (REE) although the underlying mechanisms remain poorly understood. Browning corresponds to the activation of inducible brown adipocytes in white adipose tissue (WAT) and participates in cachexia associated with hypermetabolic diseases such as cancers. The objective of this study is to highlight a phenomenon of browning associated with CKD and to study the potential role of uremic toxins in the activation of this phenomenon.


3T3L1 mouse adipocytes were incubated for 24h with plasma (20% v/v) from healthy volunteers or chronic haemodialysis patients; or with two major uremic toxins (p-Cresyl sulfate and Indoxyl-sulfate). We quantitated the content of uncoupling protein 1 (UCP-1) recognized as a hallmark of browning and studied the adipocytes differentiation. In vivo, study was carried out on 5/6 nephrectomy mice with measurement of indirect REE, WAT UCP-1 expression and content after 3 weeks of uremia.


The incubation of 3T3L1 adipocytes with plasmas of uremic patients led to an increase of UCP-1 (+ 153%, p<0.001) compared to the control plasma and inhibited by cycloheximide, a protein synthesis inhibitor. Incubation of adipose cells with uremic toxins at concentrations found in CKD patients failed to alter UCP-1 synthesis or adipocytes differentiation.
CKD mice exhibited an increase in REE compared to sham mice consistent with a possible transformation of WAT into brown adipose tissue (BAT) and activation of thermogenesis. Moreover, UCP-1 content is significantly higher in CKD WAT compared to sham mice (p = 0.02) with an increase in the expression of several thermogenesis genes in the WAT of CKD mice (e.g. UCP-1, PGC1α and PRMD16).


Taken together, these data, suggest the activation of a browning phenomenon during CKD. Uremic toxins do not appear to participate in this phenomenon although p-Cresyl sulfate was previously shown to induce adipocyte dysfunction in vitro.
The activation of browning in WAT could contribute to malnutrition associated with CKD through an increase in thermogenesis and REE. Further works are needed to decipher the molecular determinants of the browning associated with CKD.


  • Private Foundation Support