RESEARCH ARTICLE Sphingolipids Are Required for Efficient

Conjugated linoleic acid (CLA) reduces adiposity in human and mouse adipocytes. This outcome is achieved through a variety of biological responses including increased energy expenditure and fatty acid oxidation, increased inflammation, repression of fatty acid bio-synthesis, attenuated glucose transport, and apoptosis. In the current study, profiling of 261 metabolites was conducted to gain new insights into the biological pathways respond-ing to CLA in 3T3-L1 adipocytes. Sphinganine and sphingosine levels were observed to be highly elevated in CLA treated adipocytes. Exogenous chemicals that increased endoge-nous ceramide levels decreased lipid levels in adipocytes, and activated AMP-activated protein kinase (AMPK) as well as NF-κB, both of which are typically activated in CLA treated adipocytes. Concurrent inhibition of ceramide de novo biosynthesis and recycling from ex-isting sphingolipid pools attenuated the lipid lowering effect normally associated with re