INTERMUSCULAR RELATIONSHIP OF HUMAN MUSCLE FIBER TYPE PROPORTIONS: SLOW LEG MUSCLES PREDICT SLOW NECK MUSCLES HARALD VIKNE, MSc, 1 KRISTIAN GUNDERSEN, PhD, 2 KNUT LIESTØL, PhD, 3 JAN MÆLEN, MD, PhD, 4 and NINA VØLLESTAD, PhD 1 1 Department of Health Sciences, University of Oslo, P.O. Box 1089 Blindern, N-0317 Oslo, Norway 2 Department of Molecular Biosciences, University of Oslo, Oslo, Norway 3 Department of Informatics, University of Oslo, Oslo, Norway 4 Department of Pathology, Oslo University Hospital–Ulleva ˚l, Ulleva ˚l, Norway Accepted 27 September 2011 ABSTRACT: Introduction: Our aim in this study was to exam- ine whether the muscle fiber type proportions in different muscles from the same individual are interrelated. Methods: Samples were excised from five skeletal muscles in each of 12 human autopsy cases, and the fiber type proportions were determined by immunohistochemistry. We further examined the intermuscu- lar relationship in fiber type proportion by reanalyzing three previously published data sets involving other muscles. Results: Subjects demonstrated a predominantly high or low proportion of type 1 fibers in all examined muscles, and the overall difference between individuals was statistically significant (P < 0.001). Accordingly, the type 1 fiber proportions in most muscles were positively correlated (median r ¼ 0.42, range 0.03–0.80). Similar results were also obtained from the three reanalyzed data sets. Conclusions: We suggest the existence of an across-muscle phenotype with respect to fiber type pro- portions; some individuals display generally faster muscles and some individuals slower muscles when compared with others. Muscle Nerve 45: 527–535, 2012 In humans, about 40% of the total body weight is skeletal muscle. Individual variation in the use of skeletal muscles is the dominant cause of variation in total energy consumption. Variation in energy consumption is also directly or indirectly influ- enced by individual variation in the metabolic properties of the skeletal muscle tissue, such as fiber type composition. In humans, the limb and trunk skeletal muscles consist of different propor- tions of three main muscle fiber types, type 1, 2A, and 2X, classified on basis of the myosin heavy chain (MyHC) they express. Most human muscles also contain a variable number of hybrid fibers that express either both type 1 and 2A MyHC (type 1/2A) or both type 2A and 2X MyHC (type 2A/X). Studies of mono- and dizygotic twins in humans 1,2 and breeding studies of rodents, 3,4 horses, 5 and pigs 6 have shown that the proportions of fiber types in single muscles are dependent on heritable factors. Under normal physiological con- ditions in humans the type 1 fibers seem to be re- sistant to change and do not switch into type 2, even when exposed to long-term training 7–13 or a long-term reduction in physical activity. 8,13–17 In contrast, a switch between the type 2 fiber subsets (2A and 2X in humans) is induced by changes in physical activity. 8,11,13,14,17 The fiber type proportions of a single muscle have been associated with outcomes of various phys- ical performance tests 18,19 and are also linked to several cardiovascular risk factors in humans. 20,21 It has been demonstrated that a high proportion of type 1 fibers in the vastus lateralis muscle is associ- ated with low blood pressure, 22 increased insulin sensitivity, 23 and other indicators of a low risk of cardiovascular disease. 21,24 Conversely, a low propor- tion of type 1 fibers in single muscles is associated with the presence of diabetes mellitus type 2, 25 pe- ripheral artery disease, 26 coronary artery disease, 27 and chronic heart failure. 28 These relationships between the fiber type proportions of one single skeletal muscle alone and cardiovascular risk factors and human performance raise the question of whether there is a systematic relationship between the fiber type proportions of different muscles in the same individual. This hypothesis was proposed by Saltin et al. in a review from 1977, 29 but we have not found any studies that address this in a system- atic fashion in humans. The main purpose of this study was to determine whether some individuals consistently display predominantly type 1 fibers or predominantly type 2 fibers in different muscles. In addition to presenting new empirical data, we have reanalyzed three previously published, independent data sets with respect to this hypothesis. 30–32 METHODS Approach to the Problem. To test the hypothesis that the distribution of fiber types in different skel- etal muscles is interrelated at the individual level we completed an autopsy study of 12 subjects. Five muscles with presumably diverse patterns of activity were excised: the sternocleidomastoideus (SCM); splenius; scalenus medius; trapezius; and vastus lat- eralis. Fiber type composition was assessed by immunohistochemistry and muscle fiber cross-sec- tional area (CSA) was completed by tracing the cell borders. In addition to our data, we tested the Abbreviations: CSA, cross-sectional area; CVD, cardiovascular disease; MyHC, myosin heavy chain; SCM, sternocleidomastoideus Correspondence to: H. Vikne; e-mail: harald.vikne@medisin.uio.no V C 2011 Wiley Periodicals, Inc. Published online 3 October 2011 in Wiley Online Library (wileyonlinelibrary. com). DOI 10.1002/mus.22315 Key words: human striated muscle, immunohistochemistry, intermuscular correlations, MyHC, skeletal muscle phenotype Intermuscular Relationship in Fiber Type Proportions MUSCLE & NERVE April 2012 527