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 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.

Returning to Play after Prolonged Training Restrictions in Professional Collision Sports

“…Skeletal muscle appears to be particularly susceptible to disuse-induced deconditioning, with substantial impairments in markers of metabolic health (reflecting declining muscle tissue quantity and quality) within just one week 53 54 . Disuse also almost immediately reduces daily muscle protein synthesis rates 55 , largely driven by a reduced ability of the inactive tissue to extract dietary derived amino acids from the circulation following each meal 56 and utilize them for the construction of new proteins 57 .…”

CrossTalk opposing view: Intramuscular lipid accumulation does not cause insulin resistance

“…1994), which is in line with our recent forearm immobilisation work demonstrating a 40% reduction in forearm glucose uptake following 2 days of disuse (Dirks et al . 2020). The rapid development of IR suggests that the removal of muscle contraction per se induces disuse‐induced IR, likely due to a lack of stimulus for translocation of the facilitative glucose transporter, GLUT4, to the plasma membrane via various signalling pathways, which is the most adjacent physiological mechanism preceding muscle glucose uptake (Richter & Hargreaves, 2013).…”

“…Nevertheless, our recently published time‐course work demonstrating a shift towards positive forearm non‐esterified fatty acid (NEFA) balance following 2 days of forearm immobilization suggests that the development of IR occurs in the same time frame as an increase in tissue NEFA uptake occurs, which implies that a causal relationship between muscle lipid accumulation and IR cannot be ruled out (Dirks et al . 2020). IMCL accumulation during disuse may also occur as a consequence of a reduction in muscle fat oxidation (Bergouignan et al .…”

“…to specifically alter NEFA availability; Dirks et al . 2020), to investigate its involvement in the development of IR.…”

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“…Though the time course and severity of some of these responses has not been precisely delineated, their integrated nature rapidly impairs oxygen (and nutrient) delivery and tissue extraction, and can be expected within < 4 weeks [52]. Skeletal muscle appears to be particularly susceptible to disuseinduced deconditioning, with substantial impairments in markers of metabolic health (reflecting declining muscle tissue quantity and quality) within just one week [53,54]. Disuse also almost immediately reduces daily muscle protein synthesis rates [55], largely driven by a reduced ability of the inactive tissue to extract dietary derived amino acids from the circulation following each meal [56] and utilize them for the construction of new proteins [57].…”