Lipoprotein Lipase in the Brain and Nervous System
Open accessAbstract
Lipoprotein lipase (LPL) is rate limiting in the provision of triglyceride-rich lipoprotein-derived lipids into tissues. LPL is also present in the brain, where its function has remained elusive. Recent evidence implicates a role of LPL in the brain in two processes: (a) the regulation of energy balance and body weight and (b) cognition. Mice with neuron-specific deletion of LPL have increases in food intake that lead to obesity, and then reductions in energy expenditure that further contribute to and sustain the phenotype. In other mice with LPL deficiency rescued from neonatal lethality by somatic gene transfer wherein LPL in the brain remains absent, altered cognition ensues. Taking into consideration data that associate LPL mutations with Alzheimer's disease, a role for LPL in learning and memory seems likely. Overall, the time is ripe for new insights into how LPL-mediated lipoprotein metabolism in the brain impacts CNS processes and systems biology.
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LPL is strongly expressed in the hypothalamus, hippocampus, and striatum.
“LPL hydrolyzes circulating chylomicrons and very-low-density lipoprotein, is a regulator of brain energy balance, is strongly expressed in the hypothalamus, hippocampus, and striatum, and LPL variants are associated with neurite pathology and Alzheimer disease [96–98].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [96]
The section ‘LPL mRNA, Protein, and Enzyme Activity in Brain and CNS’ (page not provided) reports the highest LPL mRNA levels in the hippocampus and identifies LPL mRNA in striatal neurons. The energy-balance section confirms hypothalamic LPL expression, but the paper does not establish that expression is strong in the hypothalamus or striatum. (LLM, conf=0.84)
Experimental — accuracy not yet measuredLPL variants are associated with neurite pathology and Alzheimer disease.
“LPL hydrolyzes circulating chylomicrons and very-low-density lipoprotein, is a regulator of brain energy balance, is strongly expressed in the hypothalamus, hippocampus, and striatum, and LPL variants are associated with neurite pathology and Alzheimer disease [96–98].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [96]
The “Proposed Functions of LPL in the Brain and CNS” section reports associations between some LPL variants and Alzheimer disease, while noting that findings on AD risk have been inconsistent. It also describes LPL’s role in neurite extension in cultured cells, but does not link LPL variants to neurite pathology. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredLPL hydrolyzes circulating chylomicrons and very-low-density lipoprotein.
“LPL hydrolyzes circulating chylomicrons and very-low-density lipoprotein, is a regulator of brain energy balance, is strongly expressed in the hypothalamus, hippocampus, and striatum, and LPL variants are associated with neurite pathology and Alzheimer disease [96–98].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [96]
LPL is a regulator of brain energy balance.
“LPL hydrolyzes circulating chylomicrons and very-low-density lipoprotein, is a regulator of brain energy balance, is strongly expressed in the hypothalamus, hippocampus, and striatum, and LPL variants are associated with neurite pathology and Alzheimer disease [96–98].”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [96]
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Campbell, K. S., Cawley, N. X., Luke, R., Scott, K. E. J., Johnson, N., Farhat, N. Y., Alexander, D. M., Wassif, C. A., Li, W., Cologna, S. M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22607966
Campbell, K. S., Cawley, N. X., Luke, R., Scott, K. E. J., Johnson, N., Farhat, N. Y., Alexander, D. M., Wassif, C. A., Li, W., Cologna, S. M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22607972
Campbell, K. S., Cawley, N. X., Luke, R., Scott, K. E. J., Johnson, N., Farhat, N. Y., Alexander, D. M., Wassif, C. A., Li, W., Cologna, S. M., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22607969
Xu, D. C., Sas‐Nowosielska, H., Donahue, G., Huang, H., Pourshafie, N., Good, C. R., & Berger, S. L. (2024) · Figshare · doi:10.6084/m9.figshare.26658529
Triglyceride-sensing in the mesocorticolimbic system and reward-driven behaviour control
Berland, C. (2018) · theses.fr (ABES) · doi:10.70675/3a1dc076z7d5az413czbc66z525614a40de5
- Authors
- Wang, H., & Eckel, R. H.
- Affiliations
- University of Colorado Anschutz (US)
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2012-08-21
- Volume
- 32
- Issue
- 1
- Pages
- 147-160
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- PMC
- PMC4065112
- OpenAlex
- W1990329481
- Cited by
- 105
- References
- 95
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 4 · 2020: 9 · 2019: 11 · 2018: 5 · 2017: 11 · 2016: 10 · 2015: 9 · 2014: 6 · 2013: 8
- FWCI
- 1.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089309)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- lipoprotein lipase, brain, nervous system, triglyceride-rich lipoproteins, lipoprotein metabolism, energy balance, obesity, dietary intake, energy expenditure, cognition, learning and memory, Alzheimer's disease, somatic gene transfer
- MeSH terms
- Animals, Body Weight, Brain, Central Nervous System, Energy Metabolism, Humans, Learning, Lipoprotein Lipase, Memory, Nerve Tissue Proteins, Neurons, Spinal Cord, Gene Expression Regulation, Enzymologic, Peripheral Nervous System
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