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Int J Obes (Lond). 2018 Mar;42(3):391-397. doi: 10.1038/ijo.2017.231. Epub 2017 Oct 9.

Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance.

Author information

1
Geriatrics Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.
2
Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
3
Research and Development, John Cochran Veterans Affairs Medical Center, St Louis, MO, USA.
4
Division of Geriatric Medicine, Department of Internal Medicine, Saint Louis University School of Medicine, St Louis, MO, USA.
5
Sticht Center on Aging, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Abstract

OBJECTIVE:

Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance.

DESIGN:

We used radioactively labeled triglycerides to measure blood-brain barrier (BBB) penetration, western blots to measure receptor activation, and feeding and cognitive tests to assess behavioral endpoints.

RESULTS:

Human CSF was determined to contain triglycerides, a finding previously unclear. The radioactive triglyceride triolein readily crossed the BBB and centrally administered triolein and peripherally administered lipids induced in vivo leptin and/or insulin resistance at hypothalamic receptors. Central triolein blocked the satiety effect of centrally administered leptin. Decreasing serum triglycerides with gemfibrozil improved both learning and memory inversely proportionate to triglyceride levels.

CONCLUSIONS:

Triglycerides cross the blood-brain barrier rapidly, are found in human cerebrospinal fluid, and induce central leptin and insulin receptor resistance, decreasing satiety and cognition.

PMID:
28990588
PMCID:
PMC5880581
DOI:
10.1038/ijo.2017.231
[Indexed for MEDLINE]
Free PMC Article

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