Annexin 1 Mimetic Ac2-26 Holds Promise for the Treatment of Diabetic Nephropathy

In this issue of Diabetes , Wu et al. (1) report that in a high-fat diet/streptozotocin–induced diabetes model, global annexin 1 (ANAX1) deletion exacerbates diabetic nephropathy (DN), as indicated by increased albuminuria and macrophage infiltration, increased glomerular size, mesangial expansion, glomerular basement membrane thickness, and foot process effacement, increased tubulointerstitial injury, and fibrosis. They also detected lipid accumulation and mitochondrial abnormalities in the proximal tubule epithelial cells. RNA-sequencing analysis revealed a role of ANAX1 in lipid metabolism in the HFD/STZ-induced DN mice. Using a human immortalized proximal tubule epithelial cell line, HK-2 cells, they found that ANAX1 knockdown impaired mitochondrial fatty acid oxidation via a FPR2/AMPK/PPARα/CPT2b signaling pathway, leading to reduced intracellular lipid accumulation. ANAX1 knockdown also aggravated the lipid disorders in podocytes. Finally, administration of Ac2-26, an ANAX1 mimetic, ameliorated renal …