Title
Circulating insulin stimulates fatty acid retention in white adipose tissue via KATP channel activation in the central nervous System only in insulin-sensitive mice
Author
Gaubius Instituut TNO
Coomans, C.P.
Geerling, J.J.
Guigas, B.
van den Hoek, A.M.
Parlevliet, E.T.
Ouwens, D.M.
Pijl, H.
Voshol, P.J.
Rensen, P.C.N.
Havekes, L.M.
Romijn, J.A.
Publication year
2011
Abstract
Insulin signaling in the central nervous system (CNS) is required for the inhibitory effect of insulin on glucose production. Our aim was to determine whether the CNS is also involved in the stimulatory effect of circulating insulin on the tissue-specific retention of fatty acid (FA) from plasma. In wild-type mice, hyperinsulinemic-euglycemic clamp conditions stimulated the retention of both plasma triglyceride-derived FA and plasma albumin-bound FA in the various white adipose tissues (WAT) but not in other tissues, including brown adipose tissue (BAT). Intracerebroventricular (ICV) administration of insulin induced a similar pattern of tissue-specific FA partitioning. This effect of ICV insulin administration was not associated with activation of the insulin signaling pathway in adipose tissue. ICV administration of tolbutamide, a KATP channel blocker, considerably reduced (during hyperinsulinemic-euglycemic clamp conditions) and even completely blocked (during ICV administration of insulin) WAT-specific retention of FA from plasma. This central effect of insulin was absent in CD36-deficient mice, indicating that CD36 is the predominant FA transporter in insulin-stimulated FA retention by WAT. In diet-induced insulin-resistant mice, these stimulating effects of insulin (circulating or ICV administered) on FA retention in WAT were lost. In conclusion, in insulin-sensitive mice, circulating insulin stimulates tissue-specific partitioning of plasma-derived FA in WAT in part through activation of KATP channels in the CNS. Apparently, circulating insulin stimulates fatty acid uptake in WAT but not in BAT, directly and indirectly through the CNS. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.
Subject
EELS - Earth, Environmental and Life Sciences
Life
Brain
Brown adipose tissue
Insulin resistance
Lipid metabolism
Lipoprotein lipase
Triglycerides
adenosine triphosphate sensitive potassium channel
CD36 antigen
cyclic AMP
fatty acid
insulin
leptin
serum albumin
tolbutamide
triacylglycerol
animal experiment
animal model
animal tissue
brown adipose tissue
central nervous system
channel gating
controlled study
drug administration route
drug distribution
drug half life
drug targeting
fatty acid metabolism
fatty acid retention
hormone action
hyperinsulinemia
insulin action
insulin sensitivity
male
mouse
nonhuman
signal transduction
white adipose tissue
wild type
MHR - Metabolic Health Research
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http://resolver.tudelft.nl/uuid:5f81f5ec-67ef-4655-a561-a803eaaccf8d
DOI
https://doi.org/10.1194/jlr.m015396
TNO identifier
436000
ISSN
0022-2275
Source
Journal of Lipid Research, 52 (52), 1712-1722
Document type
article