Skeletal muscle of females and males with constitutional thinness: a low intramuscular lipid content and oxidative profile

Abstract

Constitutional thinness (CT) is a non-pathological state of underweight. The present study aimed to explore skeletal muscle energy storage in individuals with constitutional thinness and to further characterize muscle phenotype at baseline and in response to overfeeding. Thirty subjects with CT (15 females, 15 males) and 31 normal-weight control subjects (16 females, 15 males) participated in the study. Histological and enzymological analyses were performed on muscle biopsies before and after overfeeding. In skeletal muscle of CT participants compared to controls, it was observed a lower content in intramuscular triglycerides for type I (p<0.01, -17%) and type IIA (p<0.05, -14%) muscle fibers, a lower glycogen content for type I fibers (p<0.01, -6%) and type IIA fibers (p<0.05, -5%), a specific fiber type distribution, a marked muscle hypotrophy (p<0.001, -20%), a low capillary-to-fiber ratio (p<0.001, -19%), and a low citrate synthase activity (p<0.05, -18%). In response to overfeeding, CT participants increased their intramuscular triglycerides content in type I (p<0.01, +10%) and type IIA (p<0.01, +9%) muscle fibers. CT individuals seem to present an unusual muscle phenotype and different adaptations to overfeeding compared to normal-weight participants, suggesting a specific energy metabolism and muscle adaptations. NCT02004821
 Novelty
 ●Low intramuscular triglycerides and glycogen content in skeletal muscle of constitutionally thin individuals
 ●Low oxidative capacity, low capillary supply, and fiber hypotrophy in skeletal muscle of constitutionally thin participants
 ●Increase in intramuscular triglycerides in constitutional thinness in response to overfeeding

Invited Letter to Editor in response to: Constitutional thinness: body fat metabolism and skeletal muscle are important factors

“…According to our results, individuals with CT, in agreement with their lower muscle mass (4,(7)(8)(9) , showed smaller fibre cross-sectional areas of all muscle fibre types compared with normal-weight participants (8,9) . They also have a lower oxidative profile with a lower capillary supply, a lower proportion of type I slow oxidative fibres in favour of a high proportion of type IIX fast glycolytic fibres, a lower citrate synthase enzyme activity and a down-regulation of genes involved in the metabolism of TAGfat storage-inducing transmembrane 1 (FITM1) and 2 (FITM2) (8,9) . Muscle fibres of CT individuals also presented lower intramuscular TAG and lower glycogen content (9) .…”

“…This hypothesis might be further supported by the high resting metabolic rate to fat-free mass ratio of CT participants observed in some studies (4,7) . Our group recently performed histochemical analyses from muscle biopsies collected in CT volunteers, in order to characterise their muscle phenotype and assess potential adaptations (8,9) . According to our results, individuals with CT, in agreement with their lower muscle mass (4,(7)(8)(9) , showed smaller fibre cross-sectional areas of all muscle fibre types compared with normal-weight participants (8,9) .…”

“…Our group recently performed histochemical analyses from muscle biopsies collected in CT volunteers, in order to characterise their muscle phenotype and assess potential adaptations (8,9) . According to our results, individuals with CT, in agreement with their lower muscle mass (4,(7)(8)(9) , showed smaller fibre cross-sectional areas of all muscle fibre types compared with normal-weight participants (8,9) . They also have a lower oxidative profile with a lower capillary supply, a lower proportion of type I slow oxidative fibres in favour of a high proportion of type IIX fast glycolytic fibres, a lower citrate synthase enzyme activity and a down-regulation of genes involved in the metabolism of TAGfat storage-inducing transmembrane 1 (FITM1) and 2 (FITM2) (8,9) .…”

“…They also have a lower oxidative profile with a lower capillary supply, a lower proportion of type I slow oxidative fibres in favour of a high proportion of type IIX fast glycolytic fibres, a lower citrate synthase enzyme activity and a down-regulation of genes involved in the metabolism of TAGfat storage-inducing transmembrane 1 (FITM1) and 2 (FITM2) (8,9) . Muscle fibres of CT individuals also presented lower intramuscular TAG and lower glycogen content (9) . CT individuals seem to present an untypical muscle phenotype, and these recent results reinforce the need for further explorations of muscle physiology but also functionality in such individuals.…”

“…It might be of particular interest to assess parameters such as strength, aerobic capacity or metabolic flexibility, in the light of our histological observations. Despite the importance of considering muscle tissue in the context of CT, this was, to the best of our knowledge, only explored in our two previous studies so far (8,9) . It therefore seems essential to achieve greater scientific and statistical power before integrating some criteria relative to muscle function in the diagnosis of CT.…”