Associations Between Lipoprotein Subfractions and Area and Density of Abdominal Muscle and Intermuscular Adipose Tissue: The Multi-Ethnic Study of Atherosclerosis.

Megan M Marron,David Herrington,Alexis C Wood,Matthew Allison,Philip Greenland,Iva Miljkovic,Britta Larsen,Alka M Kanaya

doi:10.3389/fphys.2021.713048

Abstract

Skeletal muscle quantity and quality decrease with older age, which is partly attributed to ectopic fat infiltration and has negative metabolic consequences. To inform efforts to preserve skeletal muscle with aging, a better understanding of biologic correlates of quantity and quality of muscle and intermuscular adipose tissue (IMAT) is needed. We used targeted lipidomics of lipoprotein subfractions among 947 Multi-Ethnic Study of Atherosclerosis participants to provide a detailed metabolic characterization of area and density of abdominal muscle and IMAT. Serum lipoprotein subfractions were measured at the first visit using 1H-Nuclear Magnetic Resonance spectroscopy. Muscle and IMAT area (cm2) and density (Hounsfield units) were estimated at visit 2 or 3 using computed tomography of the total abdominal, locomotion (psoas), and stabilization (paraspinal, oblique, rectus abdominis) muscles. We identified lipoprotein subfractions associated with body composition using linear regression adjusting for demographics, lifestyle, and multiple comparisons. Among 105 lipoprotein subfractions, 24 were associated with total muscle area (absolute standardized regression coefficient range: 0.07–0.10, p-values ≤ 0.002), whereas none were associated with total muscle density. When examining muscle subgroups, 25 lipoprotein subfractions were associated with stabilization muscle area, with associations strongest among the obliques. For total IMAT area, there were 27 significant associations with lipoprotein subfractions (absolute standardized regression coefficient range: 0.09–0.13, p-values ≤ 0.002). Specifically, 27 lipoprotein subfractions were associated with stabilization IMAT area, with associations strongest among the oblique and rectus abdominis muscles. For total IMAT density, there were 39 significant associations with lipoprotein subfractions (absolute standardized regression coefficient range: 0.10–0.19, p-values ≤ 0.003). Specifically, 28 and 33 lipoprotein subfractions were associated with IMAT density of locomotion and stabilization (statistically driven by obliques) muscles, respectively. Higher VLDL (cholesterol, unesterified cholesterol, phospholipids, triglycerides, and apolipoprotein B) and lower HDL (cholesterol and unesterified cholesterol) were associated with higher muscle area, higher IMAT area, and lower IMAT density. Several associations between lipoprotein subfractions and abdominal muscle area and IMAT area and density were strongest among the stabilization muscles, particularly the obliques, illustrating the importance of examining muscle groups separately. Future work is needed to determine whether the observed associations indicate a lipoprotein profile contributing to worse skeletal muscle with fat infiltration.

Highlights

Skeletal muscle and adipose tissue are endocrine organs (Ahima and Park, 2015; Choe et al, 2016) involved in multiple physiologic and pathologic processes (Miljkovic and Zmuda, 2010)
With adjustment for age, gender, race/ethnicity, alternate healthy eating index, moderate/vigorous physical activity, sedentary behavior, lipid-lowering medication use, and multiple comparisons, there were 24 lipoprotein subfractions significantly associated with total muscle area, 27 lipoprotein subfractions significantly associated with total intermuscular adipose tissue (IMAT) area, and 39 lipoprotein subfractions significantly associated with total IMAT density (Figures 1A,G,J, respectively)
When further splitting up the stabilization muscle group, we found no significant associations between lipoprotein subfractions and paraspinal IMAT area, whereas 29 lipoprotein subfractions were significantly associated with oblique IMAT area and 40 lipoprotein subfractions were associated with rectus abdominis IMAT area (Supplementary Figures 1M–O and Supplementary Table 2)

Summary

Introduction

Skeletal muscle and adipose tissue are endocrine organs (Ahima and Park, 2015; Choe et al, 2016) involved in multiple physiologic and pathologic processes (Miljkovic and Zmuda, 2010). With aging and excess caloric consumption, excess fat can accumulate in ectopic locations, including in and around skeletal muscle. This accumulation disrupts normal secretion and sensing of adipocyte-derived hormones and adipokines, triggering systemic low-grade inflammation (Richard et al, 2000). Ectopic fat accumulation impairs normal skeletal muscle metabolic function (Miljkovic and Zmuda, 2010; Correa-de-Araujo et al, 2020) and is partly responsible for adverse decreases in area (quantity) and density (quality) of skeletal muscle with aging (Evans, 1995; Goodpaster et al, 2006). To inform efforts to slow aging-related muscle atrophy and prevent muscle fat infiltration, a better understanding of biologic correlates of quantity and quality of skeletal muscle, as well as intermuscular adipose tissue (IMAT), and how the identified biologic correlates differ based on different subgroups of skeletal muscle is needed

Methods

Results

Conclusion