Deficiency of Lipoprotein Lipase in Neurons Modifies the Regulation of Energy Balance and Leads to Obesity
Open accessAbstract
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.
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LPL is expressed in the central nervous system.
“Although LPL is expressed in the central nervous system (CNS) [20,21,22], its function is less clear.”
From Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation (2021) · cites this paper as [20]
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Lipoprotein Lipase Regulates Microglial Lipid Droplet Accumulation
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- Authors
- Wang, H., Astarita, G., Taussig, M. D., Bharadwaj, K. G., DiPatrizio, N. V., Nave, K.-A., Piomelli, D., Goldberg, I. J., & Eckel, R. H.
- Affiliations
- University of Colorado Anschutz (US)
- University of California, Irvine (US)
- Columbia University (US)
- Max Planck Institute of Experimental Medicine (DE)
- Corresponding author
- Eckel, Robert H.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 13
- Issue
- 1
- Pages
- 105-113
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3034302
- OpenAlex
- W2036839499
- Cited by
- 139
- References
- 2
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 9 · 2016: 14 · 2015: 14 · 2014: 24 · 2013: 11 · 2012: 6
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Agilent Foundation
- University of California, Irvine
- Anschutz Medical Campus, University of Colorado
- National Heart, Lung, and Blood Institute (R01HL045095, HL45095, R37HL045095)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-42266, DK-073955, R01DK042266, R01DK089309, R01DK073955, P30DK048520)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- lipoprotein lipase, obesity, energy balance, hypothalamus, free fatty acids, triglyceride-rich lipoproteins, appetite regulation, agouti-related protein, neuropeptide Y, essential fatty acids, omega-3 fatty acids, hyperphagia, metabolic rate
- MeSH terms
- Animals, Brain, Energy Intake, Energy Metabolism, Fatty Acids, Nonesterified, Female, Hypothalamus, Lipoprotein Lipase, Lipoproteins, Male, Mice, Obese, Mice, Transgenic, Neurons, Obesity, Gene Expression, Mice
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