ABSTRACT
Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we found that SMS1 null mice showed lipodystrophic phenotype. Mutant mice showed up-regulation of plasma triglyceride concentrations accompanied by reduction of white adipose tissue (WAT) as they aged. Lipoprotein lipase (LPL) activity was severely reduced in mutant mice. In vivo analysis indicated that fatty acid uptake in WAT but not in liver decreased in SMS1 null compared to wild-type mice. In vitro analysis using cultured cell revealed that SMS1 depletion reduced fatty acid uptake. Proteins extracted from WAT of mutant mice were severely modified by oxidative stress, and up-regulation of mRNAs related to apoptosis, redox adjustment, mitochondrial stress response and mitochondrial biogenesis was observed. ATP content of WAT was reduced in SMS1 null mice. Blue native gel analysis indicated that accumulation of mitochondrial respiratory chain complexes was reduced. These results suggest that WAT of SMS1 null mice is severely damaged by oxidative stress and barely functional. Indeed, mutant mice treated with the anti-oxidant N-acetyl cysteine (NAC) showed partial recovery of lipodystrophic phenotypes together with normalized plasma triglyceride concentrations. Altogether, our data suggest that SMS1 is crucial to control oxidative stress in order to maintain WAT function.
Subject(s)
Adipose Tissue, White/pathology , Adipose Tissue, White/physiopathology , Oxidative Stress , Transferases (Other Substituted Phosphate Groups)/deficiency , Acetylcysteine/pharmacology , Acetylcysteine/therapeutic use , Adipose Tissue, White/drug effects , Adipose Tissue, White/metabolism , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Fatty Acids/metabolism , Hyperlipidemias/complications , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Hyperlipidemias/pathology , Lipodystrophy/complications , Lipodystrophy/drug therapy , Lipodystrophy/enzymology , Lipodystrophy/pathology , Lipoprotein Lipase/metabolism , Mice , Mice, Knockout , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondrial Turnover/drug effects , Oxidative Stress/drug effects , Phenotype , Transferases (Other Substituted Phosphate Groups)/metabolismABSTRACT
We previously reported significant body size change in the nematode Caenorhabditis elegans, depending on the food strain of E. coli. Here, we examined this body size change in 11 other nematode species as well, and found that it is common to most of these nematodes. Furthermore, this food-dependent body size change is influenced by sex and growth temperature.
