Lipid Metabolism Gets in a JAML during Kidney Disease

Abstract

It is still unclear if the ability of key regulators of actin cytoskeletal remodeling to influence lipid metabolism contributes to kidney injury. In this issue of Cell Metabolism, Fu et al. (2020) show that junctional adhesion molecule-like (JAML) is a novel mediator of glomerular disease progression while suggesting a direct link between defects in cell adhesion and lipotoxicity.

Figure 1.. A Vicious Cycle between Mitochondrial Dysfunction, Inflammation, the Cytoskeleton, and Lipid Dysmetabolism in Podocytes

In a vicious cycle, the accumulation of lipids in the form of lipid droplets in podocytes, due to altered expression of a variety of genes important in regulating lipid metabolism, leads to mitochondrial dysfunction and inflammation. Vice versa, increased mitochondrial dysfunction and inflammation can directly affect lipid metabolism. This study identifies JAML, a junction adhesion molecule (JAM)-like protein, as an important mediator regulating podocyte lipid metabolism through Sirt1-mediated SREBP1 signaling. ABCA1, ATP-binding cassette subfamily A member 1; ABCG1, ATP-binding cassette subfamily G member 1; ACC1, acetyl-CoA carboxylase alpha; ACO2, aconitase 2; APOE, apolipoprotein E; CD36, cluster of differentiation 36; CPT1, carnitine palmitoyltransferase 1A; FAS, FAS cell surface death receptor; L-FABP, fatty acid-binding protein; IL6, interleukin 6; IL18, interleukin 18; LDLR, low-density lipoprotein receptor; LXR, liver X receptor α; NLRP3, NLR family pyrin-domain-containing 3; PPARα, peroxisome proliferator-activated receptor alpha; PPARδ, peroxisome proliferator-activated receptor delta; SCAP, SREBF chaperone; SCD1, stearoyl-CoA desaturase; SREBP1c, sterol regulatory element-binding transcription factor 1; SREBP2, sterol regulatory element-binding transcription factor 2; SOAT1, sterol O-acyltransferase; TNF, tumor necrosis factor alpha.