Document Detail

Continuous 24-h nicotinic acid infusion in rats causes FFA rebound and insulin resistance by altering gene expression and basal lipolysis in adipose tissue.
MedLine Citation:
PMID:  21386057     Owner:  NLM     Status:  MEDLINE    
Nicotinic acid (NA) has been used as a lipid drug for five decades. The lipid-lowering effects of NA are attributed to its ability to suppress lipolysis in adipocytes and lower plasma FFA levels. However, plasma FFA levels often rebound during NA treatment, offsetting some of the lipid-lowering effects of NA and/or causing insulin resistance, but the underlying mechanisms are unclear. The present study was designed to determine whether a prolonged, continuous NA infusion in rats produces a FFA rebound and/or insulin resistance. NA infusion rapidly lowered plasma FFA levels (>60%, P < 0.01), and this effect was maintained for ≥5 h. However, when this infusion was extended to 24 h, plasma FFA levels rebounded to the levels of saline-infused control rats. This was not due to a downregulation of NA action, because when the NA infusion was stopped, plasma FFA levels rapidly increased more than twofold (P < 0.01), indicating that basal lipolysis was increased. Microarray analysis revealed many changes in gene expression in adipose tissue, which would contribute to the increase in basal lipolysis. In particular, phosphodiesterase-3B gene expression decreased significantly, which would increase cAMP levels and thus lipolysis. Hyperinsulinemic glucose clamps showed that insulin's action on glucose metabolism was improved during 24-h NA infusion but became impaired with increased plasma FFA levels after cessation of NA infusion. In conclusion, a 24-h continuous NA infusion in rats resulted in an FFA rebound, which appeared to be due to altered gene expression and increased basal lipolysis in adipose tissue. In addition, our data support a previous suggestion that insulin resistance develops as a result of FFA rebound during NA treatment. Thus, the present study provides an animal model and potential molecular mechanisms of FFA rebound and insulin resistance, observed in clinical studies with chronic NA treatment.
Young Taek Oh; Ki-Sook Oh; Yong Min Choi; Anne Jokiaho; Casey Donovan; Sangdun Choi; Insug Kang; Jang H Youn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-08
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  300     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-26     Completed Date:  2011-07-29     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1012-21     Citation Subset:  IM    
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA.
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MeSH Terms
Adipose Tissue / drug effects*,  metabolism*
Blotting, Western
Catecholamines / blood
Corticosterone / blood
Fatty Acids, Nonesterified / blood*
Gene Expression / drug effects
Glucose / metabolism
Glucose Clamp Technique
Glycerol / metabolism
Hypolipidemic Agents / administration & dosage,  pharmacology*
Infusions, Intravenous
Insulin Resistance / physiology*
Lipase / metabolism
Lipid Metabolism / drug effects*,  genetics*
Lipolysis / drug effects*,  genetics
Microarray Analysis
Niacin / administration & dosage,  pharmacology*
RNA / biosynthesis,  genetics
Rats, Wistar
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/Catecholamines; 0/Fatty Acids, Nonesterified; 0/Hypolipidemic Agents; 50-22-6/Corticosterone; 50-99-7/Glucose; 56-81-5/Glycerol; 59-67-6/Niacin; 63231-63-0/RNA; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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