The effects of C75, an inhibitor of fatty acid synthase, on sleep and metabolism in mice

Jacob Pellinen; Éva Szentirmai

doi:10.1371/journal.pone.0030651

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The effects of C75, an inhibitor of fatty acid synthase, on sleep and metabolism in mice

Journal article

Open access

The effects of C75, an inhibitor of fatty acid synthase, on sleep and metabolism in mice

Jacob Pellinen and Éva Szentirmai

PloS one, Vol.7(2), pp.e30651-e30651

2012

DOI: https://doi.org/10.1371/journal.pone.0030651

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https://hdl.handle.net/2376/102886

PMCID: PMC3278418

PMID: 22348016

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Abstract

Fatty Acid Synthases - antagonists & inhibitors

Animals

4-Butyrolactone - pharmacology

Enzyme Inhibitors - pharmacology

Lipid Metabolism - drug effects

Mice

4-Butyrolactone - analogs & derivatives

Sleep - drug effects

Sleep is greatly affected by changes in metabolic state. A possible mechanism where energy-sensing and sleep-regulatory functions overlap is related to lipid metabolism. Fatty acid synthase (FAS) plays a central role in lipid metabolism as a key enzyme in the formation of long-chain fatty acids. We studied the effects of systemic administration of C75, an inhibitor of FAS, on sleep, behavioral activity and metabolic parameters in mice. Since the effects of C75 on feeding and metabolism are the opposite of ghrelin's and C75 suppresses ghrelin production, we also tested the role of ghrelin signaling in the actions of C75 by using ghrelin receptor knockout (KO) mice. After a transient increase in wakefulness, C75 elicited dose-dependent and long lasting inhibition of REMS, motor activity and feeding. Simultaneously, C75 significantly attenuated slow-wave activity of the electroencephalogram. Energy expenditure, body temperature and respiratory exchange ratio were suppressed. The diurnal rhythm of feeding was completely abolished by C75. There was significant correlation between the anorectic effects, the decrease in motor activity and the diminished energy expenditure after C75 injection. We found no significant difference between wild-type and ghrelin receptor KO mice in their sleep and metabolic responses to C75. The effects of C75 resemble to what was previously reported in association with visceral illness. Our findings suggest that sleep and metabolic effects of C75 in mice are independent of the ghrelin system and may be due to its aversive actions in mice.

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Title: The effects of C75, an inhibitor of fatty acid synthase, on sleep and metabolism in mice
Creators: Jacob Pellinen - Washington, Wyoming, Alaska, Montana and Idaho, Medical Education Program, Washington State University, Spokane, Washington, United States of America
Éva Szentirmai
Publication Details: PloS one, Vol.7(2), pp.e30651-e30651
Academic Unit: Biomedical Sciences, Department of
Publisher: United States
Identifiers: 99900546542401842
Language: English
Resource Type: Journal article