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

Abstract

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: Twenty healthy males underwent seven days of forearm cast immobilization combined with a fully-controlled eucaloric (CON, n=10, age 23±2 yr, BMI 23.8±1.0 kg·m-2) or high-fat diet providing 50% excess energy from fat (HFD, 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 non-esterified 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: Seven 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 HOMA-IR or Matsuda indices. Two and seven 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 two and seven 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 is occurs as a physiological adaptation in response to the removal of muscle contraction.