Associations between lipoprotein subfractions and area and density of abdominal muscle and intermuscular adipose tissue: The Multi-Ethnic Study of Atherosclerosis

Authors: MARRON, MEGAN - University Of Pittsburgh; ALLISON, MATTHEW - University Of California, San Diego; KANAYA, ALKA - University Of California; LARSEN, BRITTA - University Of California, San Diego; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); HERRINGTON, DAVID - Wake Forest School Of Medicine; GREENLAND, PHILIP - Northwestern University; MILJKOVIC, IVA - University Of Pittsburgh

Submitted to: Frontiers in Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/2/2021
Publication Date: 9/27/2021
Citation: Marron, M.M., Allison, M., Kanaya, A.M., Larsen, B., Wood, A.C., Herrington, D., Greenland, P., Miljkovic, I. 2021. Associations between lipoprotein subfractions and area and density of abdominal muscle and intermuscular adipose tissue: The Multi-Ethnic Study of Atherosclerosis. Frontiers in Physiology. 12.Article 713048.
DOI: https://doi.org/10.3389/fphys.2021.713048

Interpretive Summary: The amount and quality of skeletal tissue decreases as people get older, a process associated with infiltration of fat into the muscle. However, little is known about why this happens, and what types of fat are involved in the process. In this study, we found a specific pattern of fat cells was associated with body composition, and the quality of muscle tissue. Future work will determine whether the observed associations indicate a causal process, whereby these fat cells directly reduce the quality of skeletal tissue, or whether another process is important for this as well as when this process starts in life.

Technical 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 (cm^2) 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.