Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Silvana Obici ,
Zhaohui Feng ,
Kimyata Morgan ,
Daniel Stein ,
George Karkanias and
Luciano Rossetti
From the Departments of Medicine and Molecular Pharmacology, Diabetes Research and Training Center, Albert Einstein College
of Medicine, Bronx, New York
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.
Footnotes
Address correspondence and reprint requests to Dr. Luciano Rossetti, Albert Einstein College of Medicine, 1300 Morris Park
Ave., Bronx, NY 10461. E-mail: rossetti{at}aecom.yu.edu .
Received for publication 3 October 2001 and accepted in revised form 26 November 2001. Posted on the World Wide Web at http://www.diabetes.org/diabetes_rapids on 20 December 2001.
aCSF, artificial cerebral spinal fluid; CNS, central nervous system; FFA, free fatty acid; GIR, glucose infusion rate; HBP,
hydroxypropyl-β-cyclodextrin; ICV, intracerebroventricular; K ATP, ATP-sensitive K + channel; LC-CoA, long-chain fatty acyl CoA; NPY, neuropeptide Y....

Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake

10.2337/diabetes.51.2.271