| Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance. | |
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MedLine Citation:
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PMID: 19906790 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. RESEARCH DESIGN AND METHODS: Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; approximately 1800 kcal; n = 11) or hypocaloric (HYPO; approximately 1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass(-1) per minute(-1)) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m(2) . min(-1)) euglycemic (5.0 mm) clamp with [3-(3)H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). RESULTS: At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 +/- 0.8, 2.0 +/- 0.5, and 2.6 +/- 0.4; HYPO, 3.8 +/- 0.5, 1.2 +/- 0.3, and 2.3 +/- 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: -42 +/- 22%; HYPO: -50 +/- 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: -15 +/- 24% vs. HYPO: -58 +/- 19%, P = 0.02). CONCLUSIONS: Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention. |
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Authors:
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Jacob M Haus; Thomas P J Solomon; Christine M Marchetti; John M Edmison; Frank González; John P Kirwan |
Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural Date: 2009-11-11 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-08 Completed Date: 2010-02-01 Revised Date: 2011-07-19 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 323-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Body Composition / physiology Diet Therapy Down-Regulation Exercise / physiology Exercise Therapy Fatty Acids, Nonesterified / blood, physiology* Female Glucose Intolerance / blood, complications, metabolism, therapy* Humans Insulin Resistance* / physiology Life Style* Liver / metabolism Male Obesity / blood, complications, metabolism, therapy* Weight Loss / physiology |
| Grant Support | |
ID/Acronym/Agency:
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1UL1-RR024989/RR/NCRR NIH HHS; HL007887/HL/NHLBI NIH HHS; MO1-RR10732/RR/NCRR NIH HHS; R01-AG12834/AG/NIA NIH HHS; RR00080/RR/NCRR NIH HHS; RR018390/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids, Nonesterified |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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