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


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.
Haus
Jacob M
JM
Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Solomon
Thomas P J
TP
Marchetti
Christine M
CM
Edmison
John M
JM
González
Frank
F
Kirwan
John P
JP
D000368:Aged; D001823:Body Composition / Q000502:physiology; D004035:Diet Therapy; D015536:Down-Regulation; D015444:Exercise / Q000502:physiology; D005081:Exercise Therapy; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000502:physiology*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008019:Life Style; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D015431:Weight Loss / Q000502:physiology
D005230:Fatty Acids, Nonesterified