Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor alpha (PPAR alpha) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPAR alpha-independent peroxisome proliferation, fenofibrate treatment was used. which was expected to significantly enhance PPAR alpha dependence in the assay system. Surprisingly, a novel type of PPAR alpha-independent peroxisome proliferation and enlargement was uncovered in PPAR alpha-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11 alpha, might be associated with the PPAR alpha-independent peroxisome proliferation at least in part. (c) 2006 Elsevier Inc. All rights reserved.