Effect of short‐term starvation versus high‐fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men

It is currently believed that intramyocellular triglyceride (IMTG) accumulation and insulin resistance are a consequence of dietary fat ingestion and/or the elevated circulating lipid levels associated with chronic fat surplus. The purpose of this study was to compare the effect of short‐term starvation versus low‐carbohydrate (CHO)/high‐fat diet on IMTG accumulation and the development of insulin resistance in physically fit men. Intramyocellular triglyceride content, measured as intramyocellular lipid (IMCL) by proton magnetic resonance spectroscopy ( 1 H‐MRS), and glucose tolerance/insulin sensitivity, assessed by frequently sampled intravenous glucose tolerance test (IVGTT), were determined after 67 h of: (a) water‐only starvation (S); and (b) very low‐CHO/high‐fat diet (LC). These diets had in common significant restriction of CHO availability but large differences in fat content. All results were compared with those measured after a mixed CHO diet (C). Dietary interventions were administered by cross‐over design. The level of dietary‐induced IMTG accumulation ( P = 0.46), insulin resistance ( P = 0.27) and glucose intolerance ( P = 0.29) was not different between S and LC treatments. Intramyocellular triglyceride content and insulin sensitivity were negatively correlated ( r =−0.63, P < 0.01). Therefore, whilst insulin resistance may be due to fat accumulation at a cellular level, in the integrated human organism this outcome is not exclusively a function of dietary fat intake. The comparable level of IMTG accumulation and insulin resistance following S and LC may suggest that these metabolic perturbations are largely a consequence of the increased lipolytic response associated with CHO restriction.