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Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Abstract
The hypothalamus and other regions within the central nervous system (CNS) link the sensing of nutrients to the control of metabolism and feeding behavior. Here, we report that intracerebroventricular (ICV) administration of the long-chain fatty acid oleic acid markedly inhibits glucose production and food intake. The anorectic effect of oleic acid was independent of leptin and was accompanied by a decrease in the hypothalamic expression of neuropeptide Y. The short-chain fatty acid octanoic acid failed to reproduce the metabolic effects of oleic acid, and ICV coadministration of inhibitors of ATP-sensitive K+ channels blunted the effect of oleic acid on glucose production. This is the first demonstration that fatty acids can signal nutrient availability to the CNS, which in turn limits further delivery of nutrients to the circulation.
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“pharmacological interventions designed to block LCFA oxidation by increasing malonyl CoA levels (e.g. oleic acid, fatty acid synthase (FAS) inhibitor) in the CNS reduce food intake and HGP (99, 107, 133, 147)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [133]
In the citing paper
“Although accumulating evidence suggests that leptin (10 -13), insulin (14,15), and nutrient-related signals (16 -18) in the CNS improve hepatic insulin sensitivity”
From Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia (2011) · cites this paper as [16]
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Metadata
- Authors
- Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-02-01
- Volume
- 51
- Issue
- 2
- Pages
- 271-275
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2148366635
- Cited by
- 654
- References
- 27
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 12 · 2023: 19 · 2022: 14 · 2021: 19 · 2020: 22 · 2019: 19 · 2018: 20 · 2017: 34 · 2016: 28 · 2015: 41 · 2014: 36 · 2013: 36 · 2012: 30
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-48321, DK20541, DK-45024)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- oleic acid, long-chain fatty acids, glucose production, dietary intake, anorectic effect, hypothalamus, neuropeptide Y, octanoic acid, short-chain fatty acids, ATP-sensitive potassium channels, nutrient sensing, intracerebroventricular administration
- MeSH terms
- Adenosine Triphosphate, Animals, Eating, Glucose, Hypothalamus, Injections, Intraventricular, Insulin, Male, Neuropeptide Y, Sulfonylurea Compounds, Potassium Channels, Rats, Sprague-Dawley, Oleic Acid, Third Ventricle, Potassium Channel Blockers, Rats
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