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Deficiency of lipoprotein lipase in neurons modifies the regulation of energy balance and leads to obesity.

Abstract
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.
AuthorsHong Wang, Giuseppe Astarita, Matthew D Taussig, Kalyani G Bharadwaj, Nicholas V DiPatrizio, Klaus-Armin Nave, Daniele Piomelli, Ira J Goldberg, Robert H Eckel
JournalCell metabolism (Cell Metab) Vol. 13 Issue 1 Pg. 105-13 (Jan 05 2011) ISSN: 1932-7420 [Electronic] United States
PMID21195353 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Fatty Acids, Nonesterified
  • Lipoproteins
  • Lipoprotein Lipase
Topics
  • Animals
  • Brain (metabolism)
  • Energy Intake
  • Energy Metabolism
  • Fatty Acids, Nonesterified (metabolism)
  • Female
  • Gene Expression
  • Hypothalamus (metabolism)
  • Lipoprotein Lipase (deficiency, genetics, metabolism)
  • Lipoproteins (metabolism)
  • Male
  • Mice
  • Mice, Obese
  • Mice, Transgenic
  • Neurons (enzymology)
  • Obesity (enzymology, genetics, metabolism, pathology)

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