Intramuscular Adipose Tissue Research Articles

Relationship between adiponectin and intramuscular fat content determined by ultrasonography in older adults.

Age-associated intramuscular adipose tissue (IntraMAT) deposition induces the development of insulin resistance and metabolic syndrome. However, the relationship between IntraMAT and biochemical parameters in older adults remains unclear. The purpose of this study, therefore, was to elucidate the relationship between adiponectin and echo intensity–estimated IntraMAT using ultrasonography in normal-weight older adults (men 9, women 13) and examine biochemical parameters. Blood tests were performed to determine fasting levels of glucose, insulin, hemoglobin A1c, total cholesterol (Total-C), high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol (LDL-C), free fatty acid, triglycerides (TGs), adiponectin, leptin, high-sensitivity C-reactive protein, and high-sensitivity tumor necrosis factor, and homoeostasis model assessment index of insulin resistance (HOMA-IR). Mean gray-scale echo intensity was calculated as the IntraMAT index of the vastus lateralis. Waist circumference was measured at the level of the navel as the visceral adipose tissue (VAT) index. Echo intensity was significantly inversely correlated with adiponectin or LDL-C, and that was significantly positively correlated with TG. Adiponectin level was inversely correlated with waist circumference. Partial correlation analysis with waist circumference as the control variable revealed that adiponectin was inversely correlated with echo intensity, independent of waist circumference, whereas no such correlation was observed after controlling for LDL-C and TG levels. When biochemical parameters were grouped in the principal component analysis, among men, Total-C, insulin, and HOMA-IR or hemoglobin A1c, and high-sensitivity tumor necrosis factor–alpha were grouped with the same distribution for factors 1 and 2. Among women, glucose, insulin, HOMA-IR, and Total-C or TGs were grouped with the same distribution for factors 1 and 2. These data suggest that adiponectin level is related to IntraMAT content, independent of VAT in normal-weight older adults. The dynamics of adiponectin might not be similar to those of other circulating biochemical parameters in older men and women.

Intramuscular adipogenesis in cattle: Effects of body fat distribution and macrophage infiltration.

Ectopic fat is defined by the deposition of adipose tissue within non-adipose tissue such as skeletal muscle. Japanese Black cattle (Wagyu) are characterized by the ability to accumulate high amounts of intramuscular adipose tissue. Obese conditions enhance the accumulation of ectopic fat. This review shows the effects of subcutaneous and visceral fat distribution on Wagyu intramuscular adipogenesis. Obese conditions also stimulate the macrophage infiltration into adipose tissues. Adipose tissue macrophages have reported to regulate adipose tissue growth and ectopic fat accumulation in humans and rodents. Wagyu is characterized by the higher capacity for intramuscular adipogenesis than Holsteins. This review discusses the depot-specific effects of macrophage infiltration among subcutaneous, visceral, and intramuscular adipose tissue on intramuscular adipogenesis in Wagyu and Holstein cattle. Recently, metabolome analysis has been used to identify obesity-related biomarkers by comparing the biological samples between lean and obese patients. This review introduces the metabolomic profiles of plasma and intramuscular adipose tissue between Wagyu and Holsteins.

STATIN USE IS ASSOCIATED WITH SUBTLE CHANGES IN MUSCLE COMPOSITION AND QUALITY: A QUANTITATIVE IMAGING ANALYSIS USING OAI DATA

Subjective statin-associated musculoskeletal symptoms such as myalgia are commonly reported and contribute to statins' non-adherence. Several trials have recently suggested that in the absence of rare myositis, such symptoms are probably a placebo effect. However, no longitudinal study has been conducted to investigate whether statin use can be associated with deterioration in muscle quality. Such an association can be of particular clinical concern in older patients with or at-risk of knee OA, in whom muscle changes can affect the knee OA clinical outcomes. To assess longitudinal changes of validated thigh muscle quality biomarkers associated with statin use in people with or at-risk of knee OA. OAI Statin users at baseline or any of the four annual follow-up visits and non-users were matched for confounding by indication using 1:1 propensity-score (PS) matching. Potential confounders as covariates of the PS-matching included a wide range of demographic variables, comorbid diseases, risk factors, and medications. After PS-matching, 3,772 thighs of 1,910 participants were included (1,886 thighs of statin-users: 1,886 of non-users; age: 62±9 years (average ± SD), range: 45-79; female/male ratio: 1). Participants were further stratified according to baseline radiographic knee OA status (with versus at-risk of knee OA). We trained, tested, and used an automated deep learning model with a 2D U-Net structure to segment thigh muscle MRIs, with similar results to manual segmentation and quantification. Longitudinal muscle quality biomarkers included cross-sectional area (CSA), intramuscular adipose tissue (intra-MAT), contractile percent, and knee extensors and flexors maximum contractile force and specific contractile force (contractile force/CSAs) at baseline, 2nd, and 4th-year follow up. Linear mixed-effects models were used. At baseline, there was no statistically significant imbalance in PS-matching variables or muscle quality biomarkers between PS-matched statin-users and non-users. During four years, statin use was associated with a slight decrease in muscle quality, indicated by decreased knee extensor (quadriceps) maximum and specific contractile forces (mean difference (% of baseline value), 95%CI: -1.85 Newton/year (0.5% of 355.15N at baseline), -3.23 – -0.47, and -0.04 N/cm2/year (0.6% of 6.96N/cm2 at baseline), -0.07 – -0.01), contractile percent of the thigh muscles (-0.03%/year (0.03% of 95.32% at baseline), -0.06 – -0.01), and increased thigh intra-MAT (3.06 mm2/year (0.7% of 461.45mm2 at baseline), 0.53–5.59). However, stratification analysis showed that these results were only present in participants at-risk of knee OA but not those with the existing radiographic knee OA at baseline. Statin use is associated with decreased muscle quality, indicated by reduced contractility of the extensor (quadriceps) muscle and increased intra-muscular fat deposition. However, considering the small size of changes in muscle quality compared to substantial favorable cardiovascular effects of statins in clinical practice, these muscle changes might be considered clinically negligible. NIH NIAMS, under Award Number R01AR079620-01. AG reported receiving funding from Merck Serono, AstraZeneca, Galapagos, Pfizer, Roche, TissueGene (for consultation), and Boston Imaging Core Lab (as the president and stockholder). SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). CORRESPONDENCE ADDRESS: sdemehri1@jhmi.edu

THIGH MUSCLE CHANGES CAN WORSEN SUBSEQUENT KNEE OA CLINICAL OUTCOMES: USE OF DEEP LEARNING AND PROPENSITY-SCORE MATCHING ON OAI DATA

Thigh muscles play an important role in knee joint biomechanical stability, and changes in their size and quality are associated with knee OA incidence. There are currently no known disease-modifying medications for mitigating knee OA-related symptom worsening and delaying TKA. Therefore, non-surgical, non-pharmacological approaches targeting thigh muscle strengthening and composition have important clinical implications. The structural therapeutic effects of such interventions can be quantified using muscle MRI. However, no conclusive longitudinal data is available on the association of quantitative thigh muscle MRI markers with knee OA-related clinical outcomes. We aimed to investigate the longitudinal changes in quantitative muscle cross-sectional area (CSA) and adipose tissue in knee OA and their association with downstream symptom worsening and TKA. We trained, tested, and implemented a fully automated supervised deep learning model to segment longitudinal thigh MRIs of a large sample of the OAI participants. In an analysis of OAI data, knees of participants with available quality thigh MRIs at baseline and at least one follow-up visit were included and classified as with and without knee OA according to baseline radiographic KLG ≥2 and matched for confounders using propensity score matching. An automated deep learning model for thigh MRI 2D-segmentation was developed and tested. Markers of muscle CSA and intramuscular adipose tissue (intra-MAT) were measured at baseline, 2nd and 4th-years follow-up (period-1) and compared between knees with and without knee OA using linear mixed-effect regression models. Furthermore, in knees with knee OA, the association of period-1 changes in muscle markers with risk of TKA (Cox proportional-hazards) and symptom worsening (mixed-effect models) during the 4th- to 9th-year (period-2) was evaluated. This study included 4,634 matched-thighs (2,317:2,317 with:without knee OA) of 2,344 participants (mean age±SD:62±9, 1,292 females). Compared with those without, knees with knee OA had a decrease in quadriceps CSA (mean difference: -8.21mm2/year, p:.004) and an increase in quadriceps intra-MAT (1.98mm2/year, p:.007). Decreased CSA and increased intra-MAT of quadriceps during period-1 predicted downstream (period-2) knee OA symptom worsening (WOMAC total score, odds ratios:0.24 (negative association), p<.001, and 1.38, p:.019, respectively). Quadriceps CSA changes, negatively associated with higher future TKA risk (hazard ratio:0.70, p<.001). Knee osteoarthritis was associated with longitudinal MRI-derived decreased quadriceps cross-sectional area and increased intramuscular adipose tissue. These potentially modifiable risk factors predicted downstream symptom worsening and knee replacement. NIH NIA, Award Number P01AG066603 NIH NIAMS, Award Number R01AR079620-01 AG reported receiving funding from Merck Serono, AstraZeneca, Galapagos, Pfizer, Roche, TissueGene (for consultation), and Boston Imaging Core Lab (as the president and stockholder). SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). Authors acknowledge OAI staff and team. CORRESPONDENCE ADDRESS: Mohajer.bahram@gmail.com .

Prognostic Impact of Quality and Distribution of Adipose Tissue in Patients With Primary Central Nervous System Lymphoma.

Body composition assessment has shown promising results as a prognostic biomarker as depicted by cross-sectional imaging of several tumor entities including lymphomas. The present study sought to elucidate the prognostic relevance of subcutaneous and visceral fat tissue (SAT and VAT) in patients with primary central nervous system lymphoma (PCNSL). Overall, 74 patients (36 female patients, 46.7%) with a mean age of 64.2±12.8 years (range=23-81 years) were identified in the database with sufficient clinical and imaging data and included into this retrospective study. Fat area assessment was performed on one axial slide on L3-height derived from staging computed tomography (CT) images. Subcutaneous, visceral, and intramuscular adipose tissues (SAT, VAT, IMAT) were estimated. Also, density of SAT, VAT, and IMAT were estimated. Finally, the ratio VAT/SAT (VSR) was calculated. Overall and progression-free survival (OS and PFS) were used as study end points. In the observation period, overall, 47 patients (63.5%) died. Mean OS was 33.8±45.4 months and mean PFS was 26.6±42.7 months. The mean VAT value was 162±99.5 cm2, the mean SAT was 202.4±103.3 cm2, the mean VSR was 0.92±0.69. The hazard ratios (HRs) for overall survival were 0.87 for high VAT, 1.52 for SAT, and 0.73 for VSR in univariable analysis. For PFS it was 0.24 for VAT, 1.11 for SAT, and 1.07 for VSR. No values achieved statistical significance. Similar results were shown in Kaplan-Meier analysis for OS and PFS, respectively. Parameters of adipose tissue are not associated with OS and PFS in patients with PCNSL.

Muscle Quality Predicts Outcomes after Surgery for Early-Stage Non-Small-Cell Lung Cancer.

Purpose: This study investigated the impact of skeletal muscle quality on the outcomes of patients undergoing surgery for early-stage non–small-cell lung cancer (NSCLC).Methods: A total of 98 patients with pathological stage I–II NSCLC who underwent lobectomy or segmentectomy were retrospectively analyzed. Along with skeletal muscle quantity, muscle quality was evaluated by intramuscular adipose tissue content (IMAC) at the first lumbar vertebral level; a higher IMAC indicates lower skeletal muscle quality. Patients were divided into two groups according to the gender-specific quartiles of IMAC, and the prognostic impact of IMAC was investigated.Results: No significant differences in the body and skeletal mass indices, which indicate skeletal muscle quantity, were observed between patients with high and those with normal IMAC. Patients with high IMAC (n = 23) showed a significantly poorer prognosis in overall and disease-specific survivals than those with normal IMAC (n = 75; P <0.001 and P = 0.048, respectively). In a bivariate analysis that included other clinicopathological factors, a high IMAC was independently associated with worse overall survival.Conclusion: The skeletal muscle quality evaluated by IMAC could be used to predict survival risk after surgery for early-stage NSCLC.

LEVOTHYROXINE USE MAY BE ASSOCIATED WITH LONGITUDINAL QUADRICEPS ATROPHY AND SUBSEQUENT KNEE OA RISK: PRELIMINARY ANALYSIS FROM OAI COHORT

Levothyroxine, the primary treatment for hypothyroidism, is prescribed for more than 7% of Americans. Levothyroxine use, or the underlying hypothyroidism can be associated with musculoskeletal symptoms; however, no prior work has investigated this association using sensitive biomarkers. We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in participants at-risk of knee OA and their mediatory role in subsequent knee OA radiographic and symptomatic incidence. Thighs and knees of OAI participants without established radiographic knee OA were included. Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th-year and were matched with nonusers for potential confounders using 1:2/3 propensity-score (PS) matching. We developed and validated a deep learning method for automated thigh segmentation and assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intramuscular adipose tissue (intra-MAT), contractile percentage, and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard knee OA radiographic and symptomatic incidence. Finally, we assessed whether the association between levothyroxine use and knee OA incidence is mediated via muscle changes. We included 1485 matched thighs/knees (387:1098 users:non-users; age: 62±9 years, female/male:3.1). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI:-15.46mm2/year, -25.11– -5.82) but not thigh muscles’ composition biomarkers. Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR):1.59, 1.15–2.20) and symptomatic knee OA incidence (HR:1.60, 1.12–2.29). A decrease in quadriceps CSA partially mediated the increased risk of knee OA incidence associated with levothyroxine use. Our exploratory analyses suggest that levothyroxine users might have increased risk of thigh muscle atrophy and subsequent knee OA. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier and therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal thigh muscles atrophy and associated knee OA incidence risk. NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R01AR079620-01. AG reported receiving funding from Merck Serono, AstraZeneca, Galapagos, Pfizer, Roche, TissueGene (for consultation), and Boston Imaging Core Lab (as the president and stockholder). SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). Authors acknowledge OAI staff and team. CORRESPONDENCE ADDRESS: sdemehri1@jhmi.edu .

Investigation of the Relationship between the Mid_Thigh Adipose Tissue Distribution Measured by MRI and Serum Osteocalcin-A Sex-Based Approach.

Osteocalcin, in its non-carboxylated form, has a positive effect on glucose metabolism. Additionally, osteocalcin levels are related to body composition, especially muscle mass. The relation to the distribution of different adipose tissue types, such as subcutaneous, intermuscular, and visceral adipose tissue, is unclear. This study aimed to investigate associations between serum osteocalcin and the distribution of subcutaneous and intermuscular adipose tissue of the mid-thigh. Furthermore, the influence of different training methods on osteocalcin levels was investigated. We performed adipose tissue quantification of subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) using MRI measurements of the mid-thigh in 128 volunteers (63 male/65 female). Laboratory analysis included blood lipid panel, serum insulin, adiponectin, and osteocalcin measurements. The main observation was a significant correlation of total serum osteocalcin (TOC) and the distribution of adipose tissue of the mid-thigh (SAT/(SAT + IMAT)) (cc = −0.29/p-value = 0.002), as well as the cross-sectional muscle area (MA), increasing with the weekly resistance training duration in males. Additionally, TOC (p-value = 0.01) and MA (p-value = 0.03) were negatively related to serum insulin. The significant relationship between TOC and SAT/(SAT + IMAT) is a new finding and confirms the negative influence of IMAT on glucose metabolism in a sex-specific approach. We could substantiate this by the negative relation of TOC with serum insulin.

Influence of Subcutaneous Adipose Tissue and Skeletal Muscle Thickness on Rectus Femoris Echo Intensity in Younger and Older Males and Females.

Ultrasound measurements of muscle echo intensity are commonly used surrogates of muscle composition (eg, intramuscular adipose tissue). However, given that soundwaves are increasingly attenuated with tissue depth, the interpretation of echo intensity may be confounded by adipose and skeletal muscle thickness. Our objectives are to compare the associations between adipose or muscle tissue thickness and rectus femoris echo intensity in younger and older males and females. Participants included in this analysis were derived from 3 previously published cohorts of younger (<45 years) and older (≥60 years) males and females. Ultrasound images of the rectus femoris were evaluated for muscle thickness, echo intensity, and subcutaneous adipose tissue thickness. Older adults (n: 49 males, 19 females) had a higher body mass index (P=.001) compared with younger adults (n: 37 males, 49 females). Muscle thickness was negatively associated with echo intensity in older males (r=-0.59) and females (r=-0.53), whereas no associations were observed in younger males (r=0.00) or females (r=-0.11). Subcutaneous adipose tissue thickness displayed no associations with echo intensity in any group. Despite the known influence of subcutaneous adipose tissue thickness on beam attenuation, we observed no association with muscle echo intensity, indicating that adipose tissue correction may be required to better understand muscle echo intensity across differences in adiposity. The negative associations between muscle thickness and echo intensity in older, but not younger adults, suggests these associations may be related to the co-occurrence of skeletal muscle atrophy and intramuscular adipose tissue infiltration with advancing age.

Metabolomic analysis of plasma and intramuscular adipose tissue between Wagyu and Holstein cattle.

In this experiment, we studied the effects of breed differences in intramuscular adipogenic capacity on the metabolomic profiles of plasma and intramuscular adipose tissue between Wagyu (high intramuscular adipogenic capacity) and Holstein (low intramuscular adipogenic capacity) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). We showed that the intramuscular fat content, intramuscular adipocyte size and the expression of adipogenic transcription factors (C/EBPβ and C/EBPα) of Wagyu were significantly higher than those of Holstein. Metabolites detected at significantly higher levels in Wagyu plasma were related to the tricarboxylic acid cycle, lipid synthesis, fatty acid metabolism, diabetes, and glucose homeostasis. In contrast, metabolites detected at significantly higher levels in Holstein plasma were related to choline metabolism, the ethanolamine pathway, glutathione homeostasis, nucleic acid metabolism, and amino acid metabolism. Metabolites detected at significantly higher levels in Holstein intramuscular adipose tissue were related to nucleic acid metabolism, amino acid metabolism, amino sugar metabolism, beta oxidation, and the ethanolamine pathway. There were no metabolites significantly higher levels in Wagyu intramuscular adipose tissue. These results indicate candidate biomarkers of breed differences in intramuscular adipogenic capacity between Wagyu and Holstein.

Effects of Dietary Protein Concentration on Lipid Metabolism Gene Expression and Fatty Acid Composition in 18-23-Month-Old Hanwoo Steers.

Simple SummaryIntramuscular fat or fatty acids content was regarded as a quality index of meat as it increases meat tenderness and flavor. In Korea, commercial Hanwoo farms have been supplying concentrate feeds that are 2–3% higher in crude protein (CP) content rather than conventional feeds throughout the entire program and have tried to shorten the feeding period to less than 28 months of age. This has led to a probable stability in lean-to-fat ratio in Hanwoo steers from 19 to 21 months of age. This stability could be linked to the regulation of the gene expression mediating lipogenesis during this phase. However, there is a lack of data regarding the effects of the protein level in isoenergetic concentrate diets on transcriptional activity of such genes at this phase. The conventional feeding program and the current one with relatively higher CP content were compared in two groups of twenty Hanwoo steers. Results showed that higher CP endorsement during the growing phase increased the expression of intramuscular PPARα (p < 0.1) and LPL (p < 0.05) and decreased the genes, such as VLCAD (p < 0.01), GPAT1 (p = 0.001), and DGAT2 (p = 0.016), which are involved in lipogenesis and fatty acid esterification. This may result in a relatively lower lipid turnover which could be responsible for shortening the feeding period.The present study evaluated the influence of dietary protein level on growth performance, fatty acid composition, and the expression of lipid metabolic genes in intramuscular adipose tissues from 18- to 23-month-old Hanwoo steers, representing the switching point of the lean-to-fat ratio. Forty steers with an initial live weight of 486 ± 37 kg were assigned to one of two treatment groups fed either a concentrate diet with 14.5% CP and or with 17% CP for 6 months. Biopsy samples of intramuscular tissue were collected to analyze the fatty acid composition and gene expression at 23 months of age. Throughout the entire experimental period, all steers were restrained twice daily to allow individual feeding. Growth performance, blood metabolites, and carcass traits, according to ultrasonic measurements, were not affected by the experimental diets. The high-protein diet significantly increased the expression of intramuscular PPARα (p < 0.1) and LPL (p < 0.05) but did not affect genes involved in fatty acid uptake (CD36 and FABP4) nor lipogenesis (ACACA, FASN, and SCD). In addition, it downregulated intramuscular VLCAD (p < 0.01) related to lipogenesis but also GPAT1 (p = 0.001), DGAT2 (p = 0.016), and SNAP23 (p = 0.057), which are involved in fatty acid esterification and adipocyte size. Hanwoo steers fed a high-protein diet at 18–23 months of age resulted in a relatively lower lipid turnover rate than steers fed a low-protein diet, which could be responsible for shortening the feeding period.

Relationship Between Body Composition and Death in Patients with COVID-19 Differs Based on the Presence of Gastrointestinal Symptoms.

BackgroundPatients with SARS-CoV-2 who present with gastrointestinal symptoms have a milder clinical course than those who do not. Risk factors for severe COVID-19 disease include increased adiposity and sarcopenia.AimsTo determine whether body composition risk factors are associated with worse outcomes among patients with gastrointestinal symptoms.MethodsThis was a retrospective study of hospitalized patients with COVID-19 who underwent abdominal CT scan for clinical indications. Abdominal body composition measures including skeletal muscle index (SMI), intramuscular adipose tissue index (IMATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio), and liver and spleen attenuation were collected. The association between body composition measurements and 30-day mortality was evaluated in patients with and without gastrointestinal symptoms at the time of positive SARS-CoV-2 test.ResultsAbdominal CT scans of 190 patients with COVID-19 were evaluated. Gastrointestinal symptoms including nausea, vomiting, diarrhea, or abdominal pain were present in 117 (62%). Among patients without gastrointestinal symptoms, those who died had greater IMATI (p = 0.049), less SMI (p = 0.010), and a trend toward a greater VAT/SAT ratio. Among patients with gastrointestinal symptoms, those who died had significantly greater IMATI (p = 0.025) but no differences in other measures.ConclusionsAmong patients with COVID-19, those without gastrointestinal symptoms showed the expected associations between mortality and low SMI, high IMATI, and trend toward higher VAT/SAT ratio, but those with gastrointestinal symptoms did not. Future studies should explore the mechanisms for the altered disease course in patients with COVID-19 who present with gastrointestinal symptoms.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10620-021-07324-4.

Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

Preoperative Muscle Strength Is a Predictor of Outcomes After Esophagectomy

BackgroundSarcopenia, loss of muscle mass and strength, has been associated with more frequent complications after esophagectomy. This study compared hand-grip strength, muscle mass, and intramuscular adipose tissue as predictors of postoperative outcomes and mortality after esophagectomy. MethodsMinimally invasive esophagectomy was performed on 175 patients with esophageal cancer. Skeletal muscle index and skeletal muscle density were derived from preoperative CTs. Hand-grip strength was measured using dynamometer. Univariate and multivariable analyses were performed. ResultsPreoperative hand-grip strength was normal in 91 (52%), intermediate in 43 (25%), and weak in 41 (23%) patients. Hand-grip strength was significantly correlated with both skeletal muscle index and skeletal muscle density. Postoperative pneumonia occurred in 8/41 (20%) patients with weak strength compared to 4/91 (4%) with normal strength (p = 0.006; Cochran-Armitage Test). Prolonged postoperative ventilation occurred in 11/41 (27%) patients with weak strength compared to 11/91 (12%) with normal strength (p = 0.036). Median length of stay was 9 days in patients with weak strength compared to 7 days for those with normal strength (p = 0.005; Kruskal–Wallis Test). Discharge to non-home location occurred in 15/41 (37%) with weak strength compared to 8/91 (9%) with normal strength (p < 0.001). Postoperative mortality at 90 days was 4/41 (10%) with weak strength compared with no mortalities (0/91) in the normal strength group (p = 0.004). Mortality at 1 year was 18/39 (46%) in patients with weak strength compared to 6/81 (7%) with normal strength, among 158 patients with 1-year follow-up (p < 0.001). ConclusionsPreoperative hand-grip strength was found to be a powerful predictor of postoperative pneumonia, length of stay, discharge to non-home location, and mortality after esophagectomy.

Comparison of metabolic risk factors, physical performances, and prevalence of low back pain among categories determined by visceral adipose tissue and trunk skeletal muscle mass in middle-aged men.

The present study compared metabolic risk factors, physical performances, and musculoskeletal impairment among categories determined by visceral adipose tissue (VAT) and trunk skeletal muscle (SM) mass in middle-aged Japanese men. In total, 1026 healthy Japanese males aged between 35 and 59years were categorized into 4 groups according to the amount of VAT and SM in the trunk measured using low-dose computed tomography (LowVAT-HighSM, LowVAT-LowSM, HighVAT-HighSM, and HighVAT-LowSM). Height, body mass waist circumference, body fat, intramuscular adipose tissue (IntraMAT), subcutaneous adipose tissue, biochemical blood profiles (triglycerides, high-density lipoprotein cholesterol, fasting blood glucose, aspartate transaminase, alanine transaminase and γ-glutamyl trans peptidase), physical performances (trunk flexibility, the chair-stand test, two-step length and hand-grip strength), the prevalence of low back pain, and lifestyle habits for exercise, alcohol intake and smoking, were compared among the groups. The results showed that LowVAT-HighSM had significantly superior biochemical blood profiles and physical performances to the other groups. HighVAT-LowSM had significantly higher %IntraMAT and the prevalence of low back pain. The two-step length, which is an index of walking ability, significantly differed according to the four subject categories. These results indicate that metabolic risk factors, physical performances, and prevalence of low back pain in middle-aged Japanese men may differ among four categories determined by VAT and trunk SM.

Sarcopenia as a Predictor of Survival in Patients with Pancreatic Adenocarcinoma After Pancreatectomy.

To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma. Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population. Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005-2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome. The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35-87 years), and median body mass index of 23kg/m2 (range: 16-40kg/m2); 77% had a Whipple procedure and 66% received adjuvant chemotherapy. Low SMI correlated with poor overall survival (OS) (P = 0.007), disease-specific survival (DSS) (P = 0.006), and recurrence-free survival (RFS) (P = 0.01). High IMAC correlated with poor OS (P = 0.04). Patients with high IMAC tended to have a shorter DSS (P = 0.09), with no correlation with RFS (P = 0.6). VSR was not associated with survival. Multivariable analysis yielded an independent association of low SMI with OS (HR = 1.7, 95%CI: 1.1-2.8, P = 0.02), DSS (HR = 1.8, 95%CI:1.03-3.2, P = 0.04), and RFS (HR = 1.8, 95%CI: 1.1-2.8, P = 0.01), and of high IMAC with OS (HR = 1.9, 95%CI: 1.1-3.1, P = 0.01). Both qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future study.

Association of preoperative muscle composition of the lower extremity with gait function after total knee arthroplasty

BackgroundLimitations of gait function persist in some patients with knee osteoarthritis after total knee arthroplasty. This study aimed to identify preoperative muscle composition variables of the operated limb associated with postoperative gait function. MethodsLongitudinal data from 45 patients who underwent unilateral primary total knee arthroplasty were retrospectively analyzed. Timed Up-and-Go test and gait speed were measured preoperatively and at 3 and 6 months postoperatively. Preoperative muscle composition in the glutei medius and minimus, the quadriceps, the hamstrings, and combination of the hamstrings and quadriceps were evaluated by computed tomography. The area ratio of the individual muscle composition to the total muscle was calculated. The factors associated with Timed Up-and-Go test and gait speed were identified using stepwise regression analysis. ResultsShorter Timed Up-and-Go test and faster gait speed at each time point correlated with higher lean muscle mass area of the total hamstrings, higher area ratio of lean muscle mass to the total hamstrings or to combination of the hamstrings and quadriceps, and lower area ratio of low density lean tissue or intramuscular adipose tissue to the total hamstrings. Shorter Timed Up-and-Go test at each time point also correlated with higher combined area of lean muscle mass of the hamstrings and quadriceps. Faster gait speed at each time point additionally correlated with lower area ratio of intramuscular fat to the total hamstrings and lower area ratio of lean tissue mass or intramuscular adipose tissue to combination of the hamstrings and quadriceps. Regression analysis using the significant muscle composition variables revealed that the area ratio of lean muscle mass to the total hamstrings was the only predictor of Timed Up-and-Go test and gait speed after operation. ConclusionsPreoperative area ratio of ipsilateral lean muscle mass to the total hamstrings could predict gait function after total knee arthroplasty.

Longitudinal relationship between intramuscular adipose tissue of the quadriceps and activities of daily living in older inpatients.

BackgroundThe longitudinal relationship between intramuscular adipose tissue of the quadriceps and activities of daily living (ADL) in older inpatients remains unclear. This study aimed to examine whether decrease of intramuscular adipose tissue of the quadriceps in older inpatients is related to the recovery of ADL than increase of muscle mass.MethodsThis longitudinal study included 202 inpatients aged ≥65 years [median age: 83.0 (77.0–88.0), 56.4% female]. Recovery of ADL during hospital stay was assessed using the change in Barthel index (BI) score (i.e. BI score at discharge minus BI score at admission) and BI score at discharge. Intramuscular adipose tissue and muscle mass of the quadriceps were assessed using echo intensity and muscle thickness on ultrasound images, respectively. Higher echo intensity indicates greater intramuscular adipose tissue. Multiple regression analysis was performed to identify the factors independently associated with the change in BI score and BI score at discharge. Changes in quadriceps echo intensity and thickness and subcutaneous fat thickness of the thigh, quadriceps echo intensity and thickness, and subcutaneous fat thickness of the thigh at admission, age, sex, days from onset disease, BI score at admission, and disease were set as independent variables.ResultsThe means of the change in quadriceps echo intensity and thickness were −2.3 ± 15.7 and 0.1 ± 0.4 cm, respectively. The median of the change in BI score was 15.0 (0.0–30.0). The quadriceps echo intensity at discharge was significantly lower than at admission (P = 0.043). The quadriceps thickness (P = 0.004) and BI score at discharge (P < 0.001) were significantly higher than those at admission. Change in quadriceps echo intensity was independently and significantly associated with the change in BI score (β = −0.25, P = 0.006) and BI score at discharge (β = −0.18, P = 0.006). In contrast, change in quadriceps thickness was not independently and significantly associated with the change in BI score (β = 0.09, P = 0.244) and BI score at discharge (β = 0.06, P = 0.244).ConclusionsOur study indicates that a decrease of intramuscular adipose tissue of the quadriceps is related to the recovery of ADL than an increase of muscle mass in older inpatients. Intramuscular adipose tissue of the quadriceps in older inpatients is considered to be a predictor for the recovery of ADL, and intervening for intramuscular adipose tissue may be important for improving ADL in older inpatients.

PSIV-14 Evidence for functional G-coupled protein receptors 43 and 120 in subcutaneous and intramuscular adipose tissue of Angus crossbred steers

Abstract We conducted experiments to demonstrate functional G-coupled protein receptor 43 (GPR43) and GPR120 in bovine intramuscular (i.m.) and subcutaneous (s.c.) adipose tissues. We hypothesized that media volatile fatty acids and long-chain fatty acids would affect cAMP concentrations differently in i.m. and s.c. adipose tissue, which would be dependent on GPR receptor populations in the adipose tissue sites. Fresh s.c. and i.m. adipose tissue from the 5th-8th longissimus thoracic rib muscle section of Angus crossbred steers (approximately 20 mo of age) was transferred immediately to 6-well culture plates containing 3 mL of KHB/Hepes/5 mM glucose. Samples were pre-incubated with 0.5 mM theophylline plus 10 μM forskolin for 30 min, after which increasing concentrations of acetate or propionate (0, 10–3, 10–2.3, and 10–3 M) in the absence or presence of 100 μM oleic acid (18:1 n-9) or 100 µM palmitic acid (16:0) were added to the incubation media. Acetate had no effect on forskolin-stimulated cAMP production in s.c. adipose tissue but decreased cAMP in i.m. adipose tissue (P &amp;lt; 0.05); this indicates a functional GPR43 receptor in i.m. adipose tissue. The combination of 10–2 M acetate and oleic acid decrease cAMP production in s.c. adipose tissue, consistent with GPR120 receptor activity, but oleic acid and palmitic acid attenuated the depression of cAMP production caused by acetate in i.m. adipose tissue. Palmitic acid depressed cAMP production in s.c. adipose tissue, and increased cAMP production in i.m. adipose tissue (P &amp;lt; 0.05). Propionate had no effect on cAMP production in s.c. or i.m. adipose tissue. These results provide evidence for functional GPR43 receptors in i.m. adipose tissue and GPR120 receptors in s.c. adipose tissue, both of which would suppress lipolysis. Further research may allow producers to increase marbling with exacerbating carcass fatness through pharmacological or dietary strategies.

Relationship between physical activity time and intramuscular adipose tissue content of the thigh muscle groups of younger and older men

We investigated the effect of physical activity on muscle tissue size and intramuscular adipose tissue (IntraMAT) content in the thigh muscle groups of younger and older men. Twenty younger and 20 older men participated in this study. The muscle tissue cross-sectional area (CSA) and the IntraMAT content in the quadriceps femoris (QF), hamstrings (HM), hip adductors (AD), and mid-thigh total were measured using magnetic resonance imaging. The physical activity time was measured using a triaxial accelerometer, and four levels of physical activity were determined depending on the metabolic equivalent of task (METs), including sedentary (≤ 1.5 METs), light intensity (≤ 2.9 METs), moderate intensity (3.0–5.9 METs), and vigorous intensity (≥ 6.0 METs). No significant correlation was observed between the physical activity parameters and muscle tissue CSA in both groups. The IntraMAT content of the three muscle groups (QF, AD, and HM) and the total thigh was inversely correlated with the time of moderate-intensity physical activity (rs = − 0.625 to − 0.489, P < 0.05, for all comparisons) in the young group, but not in the older group. These results indicate that IntraMAT accumulation was associated with the amount of moderate-physical activity in younger men.