Markers of Inflammation Are Heritable and Associated with Subcutaneous and Ectopic Skeletal Muscle Adiposity in African Ancestry Families

Abstract

Background: Skeletal muscle adipose tissue (AT) infiltration, or myosteatosis, appears to be greater in African compared with European ancestry individuals and may play a role in type 2 diabetes mellitus (T2DM), a disease that disproportionally affects African ancestry populations. Inflammation is one mechanism that may link myosteatosis with increased T2DM risk, but studies examining the relationship between inflammation and myosteatosis are lacking. Methods: To examine these associations, we measured skeletal muscle subcutaneous AT, intermuscular AT, and skeletal muscle density using quantitative computed tomography and serum markers of inflammation in 471 individuals from 8 Afro-Caribbean multigenerational families [mean family size 67; mean age 43 years; mean body mass index (BMI) 28 kg/m 2 ]. Results: After removing the variation attributable to significant covariates, heritabilities of inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a)] ranged from 33% (TNFa) to 40% (CRP); all P < 0.01. Higher CRP, IL-6, and TNF-a were associated with lower subcutaneous AT around skeletal muscle (r = -0.13 to -0.19, P < 0.05). Higher CRP was additionally associated with lower skeletal muscle density, indicative of greater intramuscular AT (r = -0.10, P < 0.05), hyperinsulinemia (r = 0.12, P < 0.05), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.17, P < 0.01). Conclusions: Our findings suggest that heredity may play a significant role in the determination of several markers of inflammation in African ancestry individuals. Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance. Longitudinal studies are needed to further evaluate the relationship between inflammation with changes in skeletal muscle AT distribution with aging and the incidence of T2DM.

Skeletal muscle density is an independent predictor of diffuse large B‐cell lymphoma outcomes treated with rituximab‐based chemoimmunotherapy

“…Ectopic fatty infiltration of skeletal muscles has been observed in other diseases such as severe type 2 diabetes, where its presence is associated with particularly poor disease control and prognosis. This altered muscle physiology in diabetes is associated with elevated serum inflammatory markers such as tumour necrosis alpha, C‐reactive protein, and interleukin‐6 . Speculating in this way, DLBCL patients with low SMD may have either more severe disease or a specific, pro‐inflammatory, host response that leads to changes in muscle physiology manifesting in both intermuscular fat deposition and poorer clinical outcomes.…”

“…SMD can vary greatly, and muscle with lower SMD has increased fat production or infiltration . In diabetes, inflammation is a proposed mechanism behind accumulation of excess intermuscular adipose tissue . Ectopic fatty infiltration of muscle may also be a phenomenon that contributes to muscle mass loss (sarcopenia) .…”

“…2 In diabetes, inflammation is a proposed mechanism behind accumulation of excess intermuscular adipose tissue. 3 Ectopic fatty infiltration of muscle may also be a phenomenon that contributes to muscle mass loss (sarcopenia). 4 Clinically, sarcopenia and cachexia are related in cancer patients, both of which have been shown to be poor prognostic indicators.…”

Adverse Fat Depots and Marrow Adiposity Are Associated With Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation

“…Similarly, quantitative CT measures of muscle density do not distinguish between intramuscular and intermuscular adipose tissue, or intracellular and intercellular lipids. However, skeletal muscle attenuation by CT has been associated with skeletal muscle lipid content, and prior studies reported associations of quantitative CT calf muscle density with insulin resistance, inflammation, and bone deficits . Finally, the study did not include dietary intake or objective measures of physical activity, such as use of accelerometers.…”

Maternal Obesity Induces Epigenetic Modifications to Facilitate Zfp423 Expression and Enhance Adipogenic Differentiation in Fetal Mice

“…Intramuscular fatty accumulation leads to muscle insulin resistance (15,16). In addition, it also impairs muscle contractile function, resulting in muscle weakness and even immobility (17).…”