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

42 Citations (Scopus)

Abstract

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
Volume95
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Glucose Intolerance
Nonesterified Fatty Acids
Insulin Resistance
Life Style
Insulin
Glucose
Liver
Fats
Nutrition
Exercise
Diet
Caloric Restriction
Aptitude
Hyperinsulinism
Heparin
Research Design
Clamping devices
Body Weight

ASJC Scopus subject areas

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

Cite this

Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance. / Haus, Jacob M.; Solomon, Thomas P J; Marchetti, Christine M.; Edmison, John M.; González, Frank; Kirwan, John P.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 95, No. 1, 01.2010, p. 323-327.

Research output: Contribution to journalArticle

Haus, Jacob M. ; Solomon, Thomas P J ; Marchetti, Christine M. ; Edmison, John M. ; González, Frank ; Kirwan, John P. / Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance. In: Journal of Clinical Endocrinology and Metabolism. 2010 ; Vol. 95, No. 1. pp. 323-327.
@article{eb96bc3a25d24d8cba2ef6759af715cc,
title = "Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance",
abstract = "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.",
author = "Haus, {Jacob M.} and Solomon, {Thomas P J} and Marchetti, {Christine M.} and Edmison, {John M.} and Frank Gonz{\'a}lez and Kirwan, {John P.}",
year = "2010",
month = "1",
doi = "10.1210/jc.2009-1101",
language = "English (US)",
volume = "95",
pages = "323--327",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance

AU - Haus, Jacob M.

AU - Solomon, Thomas P J

AU - Marchetti, Christine M.

AU - Edmison, John M.

AU - González, Frank

AU - Kirwan, John P.

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=75149132023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75149132023&partnerID=8YFLogxK

U2 - 10.1210/jc.2009-1101

DO - 10.1210/jc.2009-1101

M3 - Article

C2 - 19906790

AN - SCOPUS:75149132023

VL - 95

SP - 323

EP - 327

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -