High-fat overfeeding does not exacerbate rapid changes in forearm glucose and fatty acid balance during immobilization

Context: Physical inactivity and high-fat overfeeding have been shown to independently induce insulin resistance. Objective: Establish the contribution of muscle disuse and lipid availability to the development of inactivity-induced insulin resistance. Design, Setting, Participants, and Interventions: 20 healthy males underwent 7 days of forearm cast immobilization combined with a fully controlled eucaloric diet (n = 10, age 23 ± 2 yr, body mass index [BMI] 23.8 ± 1.0 kg·m-2) or a high-fat diet (HFD) providing 50% excess energy from fat (high-fat diet, n = 10, age 23 ± 2 yr, BMI 22.4 ± 0.8 kg·m-2). Main Outcome Measures: Prior to casting and following 2 and 7 days of immobilization, forearm glucose uptake (FGU) and nonesterified fatty acid (NEFA) balance were assessed using the arterialized venous-deep venous (AV-V) forearm balance method following ingestion of a mixed macronutrient drink. Results: 7 days of HFD increased body weight by 0.9 ± 0.2 kg (P = 0.002), but did not alter fasting, arterialized whole-blood glucose and serum insulin concentrations or the associated homeostatic model assessment of insulin resistance or Matsuda indices. Two and 7 days of forearm immobilization led to a 40 ± 7% and 52 ± 7% decrease in FGU, respectively (P < 0.001), with no difference between day 2 and 7 and no effect of HFD. Forearm NEFA balance tended to increase following 2 and 7 days of immobilization (P = 0.095). Conclusions: Forearm immobilization leads to a rapid and substantial decrease in FGU, which is accompanied by an increase in forearm NEFA balance but is not exacerbated by excess dietary fat intake. Altogether, our data suggest that disuse-induced insulin resistance of glucose metabolism occurs as a physiological adaptation in response to the removal of muscle contraction.