HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hsu, I. R Articles by Bergman, R. N Search for Related Content PubMed Articles by Hsu, I. R Articles by Bergman, R. N Agricola Articles by Hsu, I. R Articles by Bergman, R. N

Metabolic syndrome, hyperinsulinemia, and cancer^1,2,3

¹ From the Department of Physiology and Biophysics, University of Southern California, Los Angeles, CA

ABSTRACT

The term metabolic syndrome describes the association between obesity, insulin resistance, and the risk of several prominent chronic diseases, including cancer. The causal link between many of these components remains unexplained, however. What is clear are the events that precede the development of the syndrome itself. In animal models, a fat-supplemented diet causes 1) lipid deposition in adipose depots, 2) insulin resistance of liver and skeletal muscle, and 3) hyperinsulinemia. One hypothesis relating fat deposition and insulin resistance involves enhanced lipolysis in the visceral depot, which leads to an increase in free fatty acid (FFA) flux. Increased mass of stored lipid and insulin resistance of visceral adipocytes favors lipolysis. Additionally, hypersensitivity of visceral adipose cells to sympathetic nervous system stimulation leads to increased lipolysis in the obese state. However, little evidence is available for enhanced plasma FFA concentrations in the fasting state. We measured FFA concentrations over a 24-h day in obese animals and found that plasma FFAs are elevated in the middle of the night, peaking at 0300. Therefore, it is possible that nocturnal lipolysis increases exposure of liver and muscle to FFAs at night, thus causing insulin resistance, which may play a role in hyperinsulinemic compensation to insulin resistance. Nocturnal lipolysis secondary to sympathetic stimulation may not only cause insulin resistance but also be responsible for hyperinsulinemia by stimulating secretion and reducing clearance of insulin by the liver. The resulting syndrome—elevated nocturnal FFAs and elevated insulin—may synergize and increase the risk of some cancers. This possible scenario needs further study.

Key Words: Metabolic syndrome • obesity • insulin resistance • hyperinsulinemia • free fatty acids • nocturnal lipolysis • sympathetic nervous system • cancer

This article has been cited by other articles:

				J.-R. Zhou, G. L Blackburn, and W A. Walker Symposium introduction: metabolic syndrome and the onset of cancer Am. J. Clinical Nutrition, September 1, 2007; 86(3): 817S - 819S. [Abstract] [Full Text] [PDF]