Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity

Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA-mediated signaling in the brain, we created neuron-specific...

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Published inCell metabolism Vol. 13; no. 1; pp. 105 - 113
Main Authors Wang, Hong, Astarita, Giuseppe, Taussig, Matthew D., Bharadwaj, Kalyani G., DiPatrizio, Nicholas V., Nave, Klaus-Armin, Piomelli, Daniele, Goldberg, Ira J., Eckel, Robert H.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 05.01.2011
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Summary:Free fatty acids (FFAs) suppress appetite when injected into the hypothalamus. To examine whether lipoprotein lipase (LPL), a serine hydrolase that releases FFAs from circulating triglyceride (TG)-rich lipoproteins, might contribute to FFA-mediated signaling in the brain, we created neuron-specific LPL-deficient mice. Homozygous mutant (NEXLPL−/−) mice were hyperphagic and became obese by 16 weeks of age. These traits were accompanied by elevations in the hypothalamic orexigenic neuropeptides, AgRP and NPY, and were followed by reductions in metabolic rate. The uptake of TG-rich lipoprotein fatty acids was reduced in the hypothalamus of 3-month-old NEXLPL−/− mice. Moreover, deficiencies in essential fatty acids in the hypothalamus were evident by 3 months, with major deficiencies of long-chain n-3 fatty acids by 12 months. These results indicate that TG-rich lipoproteins are sensed in the brain by an LPL-dependent mechanism and provide lipid signals for the central regulation of body weight and energy balance. [Display omitted] ► Mice with lipoprotein lipase deficiency in neurons (NEXLPL) are obese ► NEXLPL mice develop obesity by modifying both food intake and energy expenditure ► NEXLPL mice have increases in hypothalamic AgRP/NPY gene expression before obesity ► NEXLPL mice demonstrate deficiencies in n-3 fatty acids in the hypothalamus
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ISSN:1550-4131
1932-7420
DOI:10.1016/j.cmet.2010.12.006