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

2021 ◽  
Vol 12 ◽  
Author(s):  
Megan M. Marron ◽  
Matthew Allison ◽  
Alka M. Kanaya ◽  
Britta Larsen ◽  
Alexis C. Wood ◽  
...  

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.

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Megan M Marron ◽  
Matthew Allison ◽  
Britta A Larsen ◽  
Joachim H Ix ◽  
Alexis C Wood ◽  
...  

Introduction: Quality and quantity of skeletal muscle decrease with age, largely due to adipose tissue infiltration, and are important determinants of metabolic health. To inform efforts to slow aging-related decline in muscle mass and prevent myosteatosis, a better understanding of the biological determinants of muscle atrophy and quality is needed. We used targeted lipidomics to identify, with a greater specificity, lipoproteins associated with muscle and intermuscular adipose tissue (IMAT) area (quantity) and density (quality) of the total abdominal, locomotion, and stabilization muscles in the Multi-Ethnic Study of Atherosclerosis. Hypothesis: Lower density lipoproteins will be positively associated with muscle and IMAT quantity, but negatively associated with quality. Methods: At visit one, 105 serum lipoproteins were measured by Bruker lipoprotein subclass analysis with 1 H-Nuclear Magnetic Resonance spectroscopy. Muscle and IMAT area (cm 2 ) and density (Hounsfield units) were estimated 2.6 years, on average, after visit 1 for the total abdominal, locomotion (psoas), and stabilization (paraspinal, oblique, and rectus abdominis) muscles from computed-tomography scans at the L4/L5 spinal junction. We identified lipoproteins associated with body composition using linear regression adjusting for age, gender, race, diet, physical activity, lipid-lowering medication, and multiple comparisons using a 1% false discovery rate. Results: Participants (N=947) were 44-84 years old (mean: 63), 51% men, 40% White, 16% Black, 16% Chinese American, and 27% Hispanic American. Among 105 lipoproteins, 24 were associated with total muscle area, whereas none were associated with muscle density. When examining specific muscle groups, 25 lipoproteins were associated with stabilization muscle area, driven by the oblique muscles. As for total IMAT area, there were 27 associations with lipoproteins. Specifically, 27 lipoproteins were associated with stabilization muscle IMAT area, driven by oblique and rectus abdominis muscles. Last, 39 lipoproteins were associated with total IMAT density, with 28 and 33 associated with locomotion and stabilization (driven by obliques) IMAT density, respectively. Higher VLDL: cholesterols, free cholesterols, phospholipids, and triglycerides and lower HDL: cholesterols and free cholesterols were associated with higher muscle area and IMAT area, but lower IMAT density (


Author(s):  
Min Jung Lee ◽  
Hong-Kyu Kim ◽  
Eun Hee Kim ◽  
Sung Jin Bae ◽  
Kyung Won Kim ◽  
...  

Objective: Low muscle mass was known to be associated with cardiovascular diseases. However, only few studies investigated the association between muscle quality and subclinical coronary atherosclerosis. Thus, we evaluated whether muscle quality measured by abdominal computed tomography is associated with the risk of coronary artery calcification. Approach and Results: We conducted a cross-sectional study on 4068 subjects without cardiovascular disease who underwent abdominal and coronary computed tomography between 2012 and 2013 during health examinations. The cross-sectional area of the skeletal muscle was measured at the L3 level (total abdominal muscle area, total abdominal muscle area) and segmented into normal attenuation muscle area, low attenuation muscle area, and intramuscular adipose tissue. We calculated the normal attenuation muscle area/total abdominal muscle area index, of which a higher value reflected a higher proportion of good quality muscle (normal attenuation muscle area) and a lower proportion of myosteatosis (low attenuation muscle area and intramuscular adipose tissue). In women, as the normal attenuation muscle area/total abdominal muscle area quartiles increased, the odds ratios (95% CIs) for significant coronary artery calcification (>100) consistently decreased (0.44 [0.24–0.80], 0.39 [0.19–0.81], 0.34 [0.12–0.98]; P =0.003) after adjusting for cardiovascular risk factors including visceral fat area and insulin resistance. In men, the odds ratios in the Q2 group were significantly lower than those in the Q1, but the association was attenuated in Q3–4 after adjustment. Conclusions: A higher proportion of good quality muscle was strongly associated with a lower prevalence of significant coronary artery calcification after adjustment, especially in women. Poor skeletal muscle quality may be an important risk factor for subclinical coronary atherosclerosis.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Adrianna I Acevedo-Fontanez ◽  
Ryan Cvejkus ◽  
Allison L Kuipers ◽  
Joseph Zmuda ◽  
Victor Wheeler ◽  
...  

Introduction: Skeletal muscle is the largest organ in the human body and vital to maintaining metabolic homeostasis. Increased skeletal muscle fat infiltration (i.e. myosteatosis) is now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. Modifications in lifestyle, such as sleep, to reduce myosteatosis would be of great public health importance. However, studies of this relationship often use subjective data and are lacking in minority populations. The aim of this study was to examine the relation between objectively measured sleep duration and myosteatosis at the calf among African Caribbeans. Methods: Data were collected on men (n=393) and women (n=438) from the Tobago Health Study. Sleep duration and physical activity was collected using a SenseWear Pro Armband (BodyMedia, Inc.). Participants were instructed to wear the armband at all times, except in water, for 4-7 days. Measures of muscle density, intermuscular adipose tissue (IMAT), and area were obtained by peripheral QCT scans of the calf (Stratec XCT-2000). Model covariates included age, sex, BMI, diabetes, alcohol intake, smoking, and moderate to vigorous physical activity (MVPA). Linear regression was used to assess the relationship of sleep duration on skeletal muscle. Results: Mean sleep duration was 5.5 hours/day (Min 2.2, Max 11.6). Overall, participants were aged 58.7 years, had a BMI of 30.2 kg/m 2 , spent an average of 42 min/day in MVPA, and 18% were diabetic. In fully adjusted models, longer sleep duration was associated with smaller muscle area, but greater muscle density and less IMAT (all P<0.03). There was no interaction of sleep and sex on muscle density, area and IMAT (p-value=0.5184; 0.2730; 0.0954). Conclusions: In African Caribbean men and women, longer sleep duration was associated with less myosteatosis, as well as, less muscle area at the calf. Further research is warranted to understand this relationship longitudinally in order to determine how it may inform lifestyle guidelines in the Caribbean.


2020 ◽  
Vol 4 (s1) ◽  
pp. 9-9
Author(s):  
Darcy Kahn ◽  
Simona Zarini ◽  
Emily Macias ◽  
Amanda Garfield ◽  
Kathleen Harrison ◽  
...  

OBJECTIVES/GOALS: Intermuscular adipose tissue (IMAT) has been associated with insulin resistance and type 2 diabetes, yet mechanistic studies addressing the functional role of IMAT are lacking. The aim of this work was to identify novel mechanisms by which IMAT may directly impact skeletal muscle metabolism. METHODS/STUDY POPULATION: We quantified the secretome of IMAT, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) to determine if there are differences between depots in the secretion of cytokines, eicosanoids, FFAs and proteins that influence metabolic function. SAT and VAT biopsies from patients undergoing laparoscopic bariatric surgery and IMAT extracted from vastus lateralis biopsies of individuals with Obesity were cultured for 48 hours in DMEM, and the conditioned media was analyzed using nanoflow HPLC-MS, multiplex ELISAs and LC/MS/MS for proteins, cytokines and eicosanoids/FFA, respectively. RESULTS/ANTICIPATED RESULTS: IMAT secretion of various extracellular matrix proteins (fibrinogen-β, collagenV1a3, fibronectin) was significantly different than VAT and SAT. Pro-inflammatory cytokine secretion of IFNg, TNFa, IL-8 and IL-13 from IMAT was higher than VAT and significantly higher than SAT (p < 0.05). IMAT secretes significantly more pro-inflammatory eicosanoids TXB2 and PGE2 than VAT (p = 0.02, 0.05) and SAT (p = 0.01, 0.04). IMAT and VAT have significantly greater basal lipolysis assessed by FFA release rates compared to SAT (p = 0.01, 0.04). DISCUSSION/SIGNIFICANCE OF IMPACT: These data begin to characterize the disparate secretory properties of SAT, VAT and IMAT and suggest a metabolically adverse secretome of IMAT, that due to its proximity to skeletal muscle may play an important functional role in the pathogenesis of insulin resistance and type 2 diabetes.


1975 ◽  
Vol 21 (1) ◽  
pp. 93-96 ◽  
Author(s):  
N. C. Stickland ◽  
G. Goldspink

SUMMARYAn ‘indicator muscle’ (m. flexor digiti V brevis) was removed in its entirety from several Large White and Landrace pigs of varying fat depth (measured over the eye-muscle area). The total muscle fibre number was measured in transverse sections for each muscle. Significant inverse relationships were found between this fibre number and fat depth measurements. These and other results suggest that fibre number is related to lean meat content. Fibre number was also shown to be highly correlated with fibre density and as thinner fibres (i.e. higher fibre density) are associated with more tender meat, fibre number may be associated with quality as well as quantity of meat.


2020 ◽  
Vol 15 (7) ◽  
pp. 926-936 ◽  
Author(s):  
Jorge L. Gamboa ◽  
Baback Roshanravan ◽  
Theodore Towse ◽  
Chad A. Keller ◽  
Aaron M. Falck ◽  
...  

Background and objectivesPatients with CKD suffer from frailty and sarcopenia, which is associated with higher morbidity and mortality. Skeletal muscle mitochondria are important for physical function and could be a target to prevent frailty and sarcopenia. In this study, we tested the hypothesis that mitochondrial dysfunction is associated with the severity of CKD. We also evaluated the interaction between mitochondrial function and coexisting comorbidities, such as impaired physical performance, intermuscular adipose tissue infiltration, inflammation, and oxidative stress.Design, setting, participants, & measurements Sixty-three participants were studied, including controls (n=21), patients with CKD not on maintenance hemodialysis (CKD 3–5; n=20), and patients on maintenance hemodialysis (n=22). We evaluated in vivo knee extensors mitochondrial function using 31P magnetic resonance spectroscopy to obtain the phosphocreatine recovery time constant, a measure of mitochondrial function. We measured physical performance using the 6-minute walk test, intermuscular adipose tissue infiltration with magnetic resonance imaging, and markers of inflammation and oxidative stress in plasma. In skeletal muscle biopsies from a select number of patients on maintenance hemodialysis, we also measured markers of mitochondrial dynamics (fusion and fission).ResultsWe found a prolonged phosphocreatine recovery constant in patients on maintenance hemodialysis (53.3 [43.4–70.1] seconds, median [interquartile range]) and patients with CKD not on maintenance hemodialysis (41.5 [35.4–49.1] seconds) compared with controls (38.9 [32.5–46.0] seconds; P=0.001 among groups). Mitochondrial dysfunction was associated with poor physical performance (r=0.62; P=0.001), greater intermuscular adipose tissue (r=0.44; P=0.001), and increased markers of inflammation and oxidative stress (r=0.60; P=0.001). We found mitochondrial fragmentation and increased content of dynamin-related protein 1, a marker of mitochondrial fission, in skeletal muscles from patients on maintenance hemodialysis (0.86 [0.48–1.35] arbitrary units (A.U.), median [interquartile range]) compared with controls (0.60 [0.24–0.75] A.U.).ConclusionsMitochondrial dysfunction is due to multifactorial etiologies and presents prior to the initiation of maintenance hemodialysis, including in patients with CKD stages 3–5.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13026-e13026
Author(s):  
Nadia Baka ◽  
Lisa Phuong ◽  
Junwen Deng ◽  
Janki Patel ◽  
Jessica Goldman ◽  
...  

e13026 Background: BC measurement can distinguish adipose tissue distribution, as well as the quantity and quality of muscle. Dysregulation in the mammalian target of rapamycin (mTOR) signaling pathway is associated with obesity and its related diseases. Everolimus (Eve), an mTOR inhibitor, is used in combination with endocrine therapy (ET) in hormone positive, HER2 negative (HR+/HER2-) MBC. However, there is limited data on the effect of Eve on BC. We aim to assess the effect of Eve on BC in patients (pts) with HR+/HER2- MBC. Methods: Pts with HR+/HER2- MBC who received Eve and ET between 2012 and 2019 at our institution were identified. We collected information about breast cancer diagnosis and treatment, weight (wt), body mass index (BMI), and computed tomography (CT). BC measurements; including skeletal muscle area (SMA), skeletal muscle density (SMD), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and muscle adiposity (MA); were analyzed at the L3 region on CT scans using Tomovision’s SliceOmatic Version 5.0. Total adipose tissue (TAT) was defined as SAT+VAT+MA. To isolate the effect of Eve on BC we also identified a cohort of pts who received ET only. We compared change in wt, BMI, and BC before and after 3 and 6 months of therapy. Wilcoxon signed rank test was used to compare BC parameters. Results: Our study included 42 pts who received Eve plus ET; 43% were Hispanic and 33% were Black. The median number of prior ET and chemotherapy lines were 1 and 0, respectively. The cohort who received ET alone included 63 patients. Median age was 68 years (interquartile range [IQR] 56-74) for the Eve and ET group and 67 years (IQR 55-74) for the ET only group (p = 0.74). Median baseline BMI was 25.8 kg/m2 (IQR 23.1-28.2) for the Eve and ET group and 28.5kg/m2 (IQR 24.2-30.8) for ET only (p = 0.08). Visceral disease was present in 24 (57%) pts on Eve and ET and 41 (65%) pts on ET only (p = 0.54). At month 3 of treatment with Eve and ET, there was a significant decrease in wt (-2.75kg, IQR -4.53-0.40, p < 0.005), BMI (-1.15kg/m2, IQR -1.71-0.14, p < 0.01), SAT (-21.93cm2, IQR -50.13-5.08, p < 0.01), and TAT (-22.34cm2, IQR -69.89-11.98, p = 0.02), which remained statistically significant at month 6 (wt: -5.70kg, IQR –7.75-1.83, p < 0.01; BMI: -2.3kg/m2, IQR -2.83-0.72, p < 0.01; SAT: -43.00cm2, IQR -73.81-10.69, p < 0.01; TAT: -32.56cm2, IQR –92.18-9.61, p = 0.03). These findings were not seen in pts who received ET only at 3 months (wt: 0.00kg, IQR –2.65-2.38, p = 0.99; BMI: 0.00kg/m2, IQR –1.07-0.91, p = 0.94; SAT: -1.82cm2, IQR -26.10-25.15, p = 0.59; TAT: 0.71cm2, IQR -44.39-27.43, p = 0.35), with similar results at 6 months. There were no statistically significant changes in VAT, SMA, SMD, or MA in both groups at 3 or 6 months. Conclusions: Everolimus is associated with decrease in SAT, with no significant change in VAT, SMA, or SMD. Further investigation is required to determine if these changes are associated with disease outcomes or everolimus toxicities.


2019 ◽  
Vol 8 (10) ◽  
pp. 1672
Author(s):  
Karolina Grąt ◽  
Ryszard Pacho ◽  
Michał Grąt ◽  
Marek Krawczyk ◽  
Krzysztof Zieniewicz ◽  
...  

Background: Body composition parameters are reported to influence the risk of hepatocellular carcinoma (HCC) recurrence after liver resection, yet data on patients undergoing liver transplantation are scarce. The aim of this study was to evaluate the impact of the amount of abdominal adipose tissue and skeletal muscles on the risk of HCC recurrence after liver transplantation. Methods: This was a retrospective observational study performed on 77 HCC patients after liver transplantation. Subcutaneous fat area (SFA), visceral fat area, psoas muscle area and total skeletal muscle area were assessed on computed tomography on the level of L3 vertebra and divided by square meters of patient height. The primary outcome measure was five-year recurrence-free survival. Results: Recurrence-free survival in the entire cohort was 95.7%, 90.8%, and 86.5% after one, three, and five years post-transplantation, respectively. SFA was significantly associated with the risk of HCC recurrence (p = 0.013), whereas no significant effects were found for visceral fat and skeletal muscle indices. The optimal cut-off for SFA for prediction of recurrence was 71.5 cm2/m2. Patients with SFA < 71.5 cm2/m2 and ≥71.5 cm2/m2 exhibited five-year recurrence-free survival of 96.0% and 55.4%, respectively (p = 0.001). Conclusions: Excessive amount of subcutaneous adipose tissue is a risk factor for HCC recurrence after liver transplantation and may be considered in patient selection process.


2016 ◽  
Vol 121 (2) ◽  
pp. 518-527 ◽  
Author(s):  
Anat Yaskolka Meir ◽  
Ilan Shelef ◽  
Dan Schwarzfuchs ◽  
Yftach Gepner ◽  
Lilac Tene ◽  
...  

It remains unclear whether intermuscular adipose tissue (IMAT) has any metabolic influence or whether it is merely a marker of abnormalities, as well as what are the effects of specific lifestyle strategies for weight loss on the dynamics of both IMAT and thigh muscle area (TMA). We followed the trajectory of IMAT and TMA during 18-mo lifestyle intervention among 278 sedentary participants with abdominal obesity, using magnetic resonance imaging. We measured the resting metabolic rate (RMR) by an indirect calorimeter. Among 273 eligible participants (47.8 ± 9.3 yr of age), the mean IMAT was 9.6 ± 4.6 cm2. Baseline IMAT levels were directly correlated with waist circumference, abdominal subdepots, C-reactive protein, and leptin and inversely correlated with baseline TMA and creatinine ( P < 0.05 for all). After 18 mo (86.3% adherence), both IMAT (−1.6%) and TMA (−3.3%) significantly decreased ( P < 0.01 vs. baseline). The changes in both IMAT and TMA were similar across the lifestyle intervention groups and directly corresponded with moderate weight loss ( P < 0.001). IMAT change did not remain independently associated with decreased abdominal subdepots or improved cardiometabolic parameters after adjustments for age, sex, and 18-mo weight loss. In similar models, 18-mo TMA loss remained associated with decreased RMR, decreased activity, and with increased fasting glucose levels and IMAT ( P < 0.05 for all). Unlike other fat depots, IMAT may not represent a unique or specific adipose tissue, instead largely reflecting body weight change per se. Moderate weight loss induced a significant decrease in thigh muscle area, suggesting the importance of resistance training to accompany weight loss programs.


2022 ◽  
Author(s):  
Dominik Lutter ◽  
Stephan Sachs ◽  
Marc Walter ◽  
Leigh Perreault ◽  
Darcy Kahn ◽  
...  

Although insulin resistance often leads to Type 2 Diabetes Mellitus (T2D), its early stages remain often unrecognized thus reducing the probability of successful prevention and intervention. Moreover, treatment efficacy is affected by the genetics of the individual patient. To identify potential candidate genes for the prediction of diabetes risk and intervention response we linked genetic expression profiles of human skeletal muscle and intermuscular adipose tissue (IMAT) to fasting glucose (FG) and glucose infusion rate (GIR). We found that genes with a strong association to these measures clustered into three distinct expression patterns. Their predictive values for insulin resistance varied strongly between muscle and IMAT. Moreover, we discovered that individual genetic expression based classifications may differ from those classifications based predominantly on clinical parameters indicating a potential incomplete patient stratification. Out of the 15 top hit candidate genes, we identified ST3GAL2, AASS, ARF1 and the transcription factor SIN3A as novel candidates for a refined diabetes risk and intervention response prediction. Our results confirm that disease progression and a successful intervention depend on individual genetics. We anticipate that our findings may lead to a better understanding and prediction of the individual diabetes risk and may help to develop individualized intervention strategies.


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