| Free fatty acids link metabolism and regulation of the insulin-sensitizing fibroblast growth factor-21. | |
| | |
MedLine Citation:
|
PMID: 19401423 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator-activator receptor (PPAR) alpha-dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPARalpha, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS: The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPARgamma activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS: Oleate and linoleate increased FGF-21 expression and secretion in a PPARalpha-dependent fashion, as demonstrated by small-interfering RNA-induced PPARalpha knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS: The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity. |
| | |
Authors:
|
Knut Mai; Janin Andres; Katrin Biedasek; Jessica Weicht; Thomas Bobbert; Markus Sabath; Sabine Meinus; Franziska Reinecke; Matthias Möhlig; Martin O Weickert; Markus Clemenz; Andreas F H Pfeiffer; Ulrich Kintscher; Simone Spuler; Joachim Spranger |
Related Documents
:
|
11238483 - Effect of protein ingestion on the glucose appearance rate in people with type 2 diabetes. 16390863 - Effects of portal free fatty acid elevation on insulin clearance and hepatic glucose flux. 7059353 - The effect of 5-methylpyrazole-3-carboxylate and nicotinic acid on abnormalities of car... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-28 |
Journal Detail:
|
Title: Diabetes Volume: 58 ISSN: 1939-327X ISO Abbreviation: Diabetes Publication Date: 2009 Jul |
Date Detail:
|
Created Date: 2009-06-30 Completed Date: 2009-07-29 Revised Date: 2010-09-27 |
Medline Journal Info:
|
Nlm Unique ID: 0372763 Medline TA: Diabetes Country: United States |
Other Details:
|
Languages: eng Pagination: 1532-8 Citation Subset: AIM; IM |
Affiliation:
|
Department of Endocrinology, Diabetes and Nutrition, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cell Line Diabetes Mellitus, Type 2 / complications, drug therapy, metabolism* Fasting / physiology* Fatty Acids, Nonesterified / metabolism* Female Fibroblast Growth Factors / genetics, metabolism* Gene Expression Regulation / drug effects Glucose Clamp Technique Glycerol / pharmacology Homeostasis Humans Hyperinsulinism / metabolism, physiopathology Hypoglycemic Agents / therapeutic use Lecithins / pharmacology Male Obesity / complications, metabolism PPAR alpha / genetics, physiology PPAR gamma / genetics, physiology* RNA, Messenger / genetics Reference Values Thiazolidinediones / therapeutic use* |
| Chemical | |
Reg. No./Substance:
|
0/Fatty Acids, Nonesterified; 0/Hypoglycemic Agents; 0/Lecithins; 0/PPAR alpha; 0/PPAR gamma; 0/RNA, Messenger; 0/Thiazolidinediones; 0/fibroblast growth factor 21; 122320-73-4/rosiglitazone; 56-81-5/Glycerol; 62031-54-3/Fibroblast Growth Factors |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Macrophages and adipocytes in human obesity: adipose tissue gene expression and insulin sensitivity ...
Next Document: Lack of Type VIII Collagen in Mice Ameliorates Diabetic Nephropathy.