Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance

Jacob M. Haus, Thomas P.J. Solomon, Christine M. Marchetti, John M. Edmison, Frank González, John P. Kirwan

Research output: Contribution to journalArticle

43 Scopus citations


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; ∼1800 kcal; n = 11) or hypocaloric (HYPO;∼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/m2 • min-1) euglycemic (5.0 mM) clamp with [3-3H]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 resistanceandHGPwasimproved only in theHYPO 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.

Original languageEnglish (US)
Pages (from-to)323-327
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - Jan 2010


ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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