The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier
Open accessAbstract
Obesity is associated with leptin resistance as evidenced by hyperleptinemia. Resistance arises from impaired leptin transport across the blood-brain barrier (BBB), defects in leptin receptor signaling, and blockades in downstream neuronal circuitries. The mediator of this resistance is unknown. Here, we show that milk, for which fats are 98% triglycerides, immediately inhibited leptin transport as assessed with in vivo, in vitro, and in situ models of the BBB. Fat-free milk and intralipid, a source of vegetable triglycerides, were without effect. Both starvation and diet-induced obesity elevated triglycerides and decreased the transport of leptin across the BBB, whereas short-term fasting decreased triglycerides and increased transport. Three of four triglycerides tested intravenously inhibited transport of leptin across the BBB, but their free fatty acid constituents were without effect. Treatment with gemfibrozil, a drug that specifically reduces triglyceride levels, reversed both hypertriglyceridemia and impaired leptin transport. We conclude that triglycerides are an important cause of leptin resistance as mediated by impaired transport across the BBB and suggest that triglyceride-mediated leptin resistance may have evolved as an anti-anorectic mechanism during starvation. Decreasing triglycerides may potentiate the anorectic effect of leptin by enhancing leptin transport across the BBB.
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Cites
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“They also have very severe hypertriglyceridemia that is reversed by treatment with leptin (45).”
BackgroundLeptin enters the brain by a saturable system independent of insulin
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Cited by
From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery
Banks, W. A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.21 · Cited by 1,204
Self-citationThe role of fructose in the pathogenesis of NAFLD and the metabolic syndrome
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Characteristics of Compounds that Cross the Blood-Brain Barrier
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Western diet consumption and cognitive impairment: Links to hippocampal dysfunction and obesity
Kanoski, S. E., & Davidson, T. L. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.12.003 · Cited by 676
Metadata
- Authors
- Banks, W. A., Coon, A. B., Robinson, S. M., Moinuddin, A., Shultz, J. M., Nakaoke, R., & Morley, J. E.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-05-01
- Volume
- 53
- Issue
- 5
- Pages
- 1253-1260
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2111732109
- Cited by
- 512
- References
- 51
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Banks, W. A., Coon, A. B., Robinson, S. M., Moinuddin, A., Shultz, J. M., Nakaoke, R., & Morley, J. E. (2004). Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier. Diabetes. https://doi.org/10.2337/diabetes.53.5.1253
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