Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
J Clin Endocrinol Metab. 2010 Jan;95(1):323-7. doi: 10.1210/jc.2009-1101. Epub 2009 Nov 11.
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.
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).
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).
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.
本研究旨在探讨运动/饮食生活方式干预对肥胖人群游离脂肪酸（FFA）诱导的肝胰岛素抵抗的影响。
23 例糖耐量受损的肥胖男性和女性（n = 23）被随机分配到运动训练的热量摄入正常组（EU；约 1800 千卡；n = 11）或热量摄入减少组（HYPO；约 1300 千卡；n = 12），持续 12 周。使用两阶段序贯高胰岛素（40 mU/m².min）正葡萄糖（5.0 mmol/L）钳夹，并用[3-³H]葡萄糖测定肝葡萄糖生成（HGP；每公斤去脂体重每分钟毫克数）和肝胰岛素抵抗。在基础状态、胰岛素输注（INS；120 分钟）和胰岛素加脂肪乳/肝素输注（INS/FFA；300 分钟）时进行测量。
在基线时，两组的基础 HGP 相似；单独使用高胰岛素血症并不能完全抑制 HGP，而 INS/FFA 的抑制作用小于 INS（EU：4.6 ± 0.8、2.0 ± 0.5 和 2.6 ± 0.4；HYPO：3.8 ± 0.5、1.2 ± 0.3 和 2.3 ± 0.4）。干预后，HYPO 组体重（P < 0.05）和脂肪量（P < 0.05）下降更多。然而，两种生活方式干预均能降低基础（P = 0.005）和 INS 时的肝胰岛素抵抗（P = 0.001），并且两组的胰岛素介导的 HGP 抑制均得到同等改善（EU：-42 ± 22%；HYPO：-50 ± 20%，干预前后，P = 0.02）。相反，只有 HYPO 组的胰岛素能够改善 FFA 诱导的肝胰岛素抵抗和 HGP（EU：-15 ± 24%对 HYPO：-58 ± 19%，P = 0.02）。
两种生活方式干预均能有效降低基础和高胰岛素状态下的肝胰岛素抵抗。然而，游离脂肪酸诱导的肝胰岛素抵抗的逆转最好通过运动/热量限制联合干预来实现。
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