Lipoprotein lipase is necessary for lipid uptake and storage by adipocytes

In vivo studies aimed at identifying the precise role of adipocyte‐derived LPL in fat storage function of adipose tissue have been unable to provide conclusive evidence due to compensatory mechanisms that activate endogenous fatty acid synthesis. To circumvent this limitation, we have measured the effects of reducing adipocyte LPL expression on intracellular lipid accumulation using a cultured model of adipocyte differentiation. During differentiation of 3T3‐L1 pre‐adipocytes, LPL mRNA expression increases 6‐fold resulting in a 2‐fold increase in cell surface‐associated LPL enzymatic activity. Parallel to this increase, intracellular lipids increased ~10‐fold demonstrating a direct correlation between adipocyte‐derived LPL expression and lipid storage. siRNA transfection of adipocytes reduced LPL mRNA expression and cell surface‐associated LPL enzymatic activity to ~50% of non‐treated controls while intracellular lipid levels were reduced by 80%. Exogenous addition of purified LPL (to restore extracellular lipolytic activity) or palmitate (as a source of free fatty acids) to siRNA‐treated cells restored intracellular lipid levels to those measured for non‐treated controls. These data demonstrate that adipocyte‐derived LPL is required for efficient fatty acid uptake and storage. This research was supported by a Grant‐in‐Aid from the American Heart Association.