Introduction:
Musculoskeletal unloading during bed rest (BR) reduces insulin-mediated glucose disposal (GD) at whole-body and limb levels [1], which develops within 24h [2]. An increase in intramyocellular lipid (IMCL) content has been proposed as a mechanistic driver of reduced GD in sedentary lean and obese individuals [3]. However, an increase in IMCL during BR could also reflect that a positive energy balance state occurred, and IMCL accumulation was not causative in any impairment of GD. We therefore measured GD and IMCL content during acute and chronic bed rest (BR) during which individuals were maintained in energy balance.
Methods:
A 3-day (acute) BR study (n=10, age 24±1.25 years, BMI 22.7±0.60 kg/m2), and a 56-day (chronic) BR study (n=20, age 34±1.8 years, BMI 23.8±0.41 kg/m2) were performed. In both, participants were exposed to -6° head-down tilt and maintained in energy balance (resting metabolic rate x 1.2) and hyperinsulinaemic euglycaemic clamps (60 mU/m2/min) were performed before and after BR to quantify whole-body GD. IMCL content was determined in pre-clamp vastus lateralis muscle biopsies before  and after BR via staining of transverse, 14 μm thick sections with the fluorescent dye Bodipy-493/503, which stains neutral lipids [4]. Additionally, fibre-type specific IMCL content was quantified following immunohistochemical staining of myosin heavy chain isoforms. Student’s T-tests and two-way repeated measures ANOVA were used for statistical analyses. Values represent mean ± SD.
Results
Steady-state insulin mediated GD was reduced from pre BR (baseline) following acute BR (13.01 ± 6.75 vs 7.75 ± 7.08 mg/kg/min, p=0.0037) and chronic BR (10.16 ± 1.89 vs 7.90 ± 1.26 mg/kg/min, p<0.0001). The magnitude of decline in GD was similar in both acute BR (17%) and chronic BR (22%). IMCL content was unchanged from baseline following acute BR (4.0±1.3% vs. 5.7±1.8%, p=0.15) and chronic BR (11.3±6.9% vs. 9.7±6.6%, p=0.69). There was a fibre type difference in IMCL content in both studies, such that type I fibre IMCL content was greater than IIA and IIX fibres, but the IMCL content of all fibre types was unchanged from baseline following acute and chronic BR (Table 1).
Conclusion
Reductions in GD following acute and chronic BR could not be explained by an increase in IMCL content or fibre-type specific IMCL responses. The IMCL accumulation reported during BR [5] appears to be a confounding factor arising from participants being in a state of positive energy balance.