| First Author | Picher-Martel V | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 6 | PubMed ID | 36982140 |
| Mgi Jnum | J:357452 | Mgi Id | MGI:7450067 |
| Doi | 10.3390/ijms24065065 | Citation | Picher-Martel V, et al. (2023) Distinct Plasma Immune Profile in ALS Implicates sTNFR-II in pAMPK/Leptin Homeostasis. Int J Mol Sci 24(6) |
| abstractText | Amyotrophic lateral sclerosis (ALS) is a clinically highly heterogeneous disease with a survival rate ranging from months to decades. Evidence suggests that a systemic deregulation of immune response may play a role and affect disease progression. Here, we measured 62 different immune/metabolic mediators in plasma of sporadic ALS (sALS) patients. We show that, at the protein level, the majority of immune mediators including a metabolic sensor, leptin, were significantly decreased in the plasma of sALS patients and in two animal models of the disease. Next, we found that a subset of patients with rapidly progressing ALS develop a distinct plasma assess immune-metabolic molecular signature characterized by a differential increase in soluble tumor necrosis factor receptor II (sTNF-RII) and chemokine (C-C motif) ligand 16 (CCL16) and further decrease in the levels of leptin, mostly dysregulated in male patients. Consistent with in vivo findings, exposure of human adipocytes to sALS plasma and/or sTNF-RII alone, induced a significant deregulation in leptin production/homeostasis and was associated with a robust increase in AMP-activated protein kinase (AMPK) phosphorylation. Conversely, treatment with an AMPK inhibitor restored leptin production in human adipocytes. Together, this study provides evidence of a distinct plasma immune profile in sALS which affects adipocyte function and leptin signaling. Furthermore, our results suggest that targeting the sTNF-RII/AMPK/leptin pathway in adipocytes may help restore assess immune-metabolic homeostasis in ALS. |
