scholarly journals Wnt Pathway Inhibitor DKK1: A Potential Novel Biomarker for Adiposity

2019 ◽  
Vol 3 (2) ◽  
pp. 488-495 ◽  
Author(s):  
Hira Ali ◽  
Joseph M Zmuda ◽  
Ryan K Cvejkus ◽  
Erin E Kershaw ◽  
Allison L Kuipers ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wnt Pathway ◽  
African Ancestry ◽  
Model Assessment ◽  
Fasting Serum ◽  
Muscle Area ◽  
Muscle Density ◽  
Muscle Adiposity ◽  
Total Body

Abstract Emerging evidence indicates that ectopic skeletal muscle adiposity may be a risk factor for type 2 diabetes (T2D), especially in persons of African ancestry. In vitro studies suggest that a Wnt pathway inhibitor, Dickkopf-related protein 1 (DKK1), plays a role in adiposity regulation and could be a biomarker for adiposity in humans. The objective of this study was to test whether serum DKK1 levels relate to adiposity measures in a cohort from an African ancestry population at high risk for T2D. Fasting serum DKK1 was measured in a sample of 159 men of African ancestry aged ≥40 years (mean age ± SD, 63.5 ± 8.2 years; mean body mass index, 27.8 ± 4.5 kg/m2). Anthropometrics included total-body and trunk adiposity measured by dual-energy x-ray absorptiometry and lower-leg skeletal muscle density measured by CT [which reflects the intramuscular adiposity content (mg/cm3)]. Serum DKK1 was positively correlated with BMI (r = 0.20; P = 0.01), waist circumference (r = 0.15; P = 0.046), DXA total-body adiposity (r = 0.24; P = 0.003), and DXA trunk adiposity (r = 0.21; P = 0.009), independent of age and height. In addition, serum DKK1 was inversely correlated with skeletal muscle density (r = −0.25; P = 0.002), independent of age, BMI, and calf muscle area. No significant correlation was found between serum DKK1 and fasting serum glucose or insulin levels or insulin resistance estimated by homeostasis model assessment. These findings suggest that higher levels of serum DKK1 may be associated with greater overall, central, and ectopic skeletal muscle adiposity. Further studies are needed to unravel the potential role of DKK1 in the regulation of adiposity in humans.

Abstract MP048: Ectopic Muscle and Liver Adiposity are Independently Associated with Type 2 Diabetes in African Ancestry Men

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Iva Miljkovic ◽  
Allison Kuipers ◽  
J Jeffrey Carr ◽  
James Terry ◽  
Sangeeta Nair ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Body Fat ◽  
African Ancestry ◽  
Ectopic Fat ◽  
Fat Depots ◽  
Total Body Fat ◽  
Muscle Adiposity ◽  
Total Body

Although obesity is a major driver of type 2 diabetes (T2D), many obese individuals do not develop T2D. Indeed, fat around and within non-adipose tissue organs (i.e., ectopic fat) is emerging as a strong risk factor for diabetes. The potential differential contribution of ectopic fat depots throughout the body on T2D risk is unclear because studies have mainly focused on visceral and/or liver fat. No study, to our knowledge, has addressed the potential independent association of visceral, liver, and skeletal muscle adiposity with T2D. Such studies are particularly needed among African ancestry populations, as generalized obesity and other risk factors do not appear to explain the high T2D burden in this population segment. To address this knowledge gap, we measured total body fat by DXA, and visceral, liver, and calf skeletal muscle adiposity by computed tomography in 490 Afro-Caribbean men, aged 50-91 years (mean age=64 years, mean BMI=27.5 kg/m 2 ). The prevalence of T2D in this population was 22.3%. We employed multiple logistic regression using total body fat percent and ectopic fat depots as predictors (Table). We found that each 7.9 HU decrease in liver attenuation (indicative of greater liver adiposity) was associated with a 33% increased odds of T2D (p=0.011). Similarly, each 4.2 mg/cm 3 decrease in muscle attenuation (indicative of greater intra-muscular adiposity) was associated with a 31% increased odds of T2D (p=0.04). These associations were independent of total and visceral adiposity. Our results support the “ectopic fat syndrome” theory, as opposed to the “portal theory”, in the pathogenesis of diabetes among African ancestry men. Longitudinal studies are needed to clarify the exact role of specific ectopic fat depots in T2D, particularly in high-risk African ancestry populations.

Abstract P070: Longer Sleep Duration Is Associated With Less Myosteatosis In African Caribbean Adults

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Adrianna I Acevedo-Fontanez ◽  
Ryan Cvejkus ◽  
Allison L Kuipers ◽  
Joseph Zmuda ◽  
Victor Wheeler ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Sleep Duration ◽  
Vigorous Physical Activity ◽  
Health Study ◽  
Muscle Area ◽  
Subjective Data ◽  
Muscle Density ◽  
Intermuscular Adipose Tissue ◽  
African Caribbean

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.

N tau-methylhistidine release: contributions of rat skeletal muscle, GI tract, and skin

1982 ◽  
Vol 243 (4) ◽  
pp. E293-E297 ◽  
Author(s):  
S. J. Wassner ◽  
J. B. Li
Keyword(s):  
Skeletal Muscle ◽  
Gastrointestinal Tract ◽  
Soft Tissue ◽  
Fractional Catabolic Rate ◽  
Gi Tract ◽  
Rat Skeletal Muscle ◽  
Catabolic Rate ◽  
Total Body

The relative contributions of skeletal muscle, gastrointestinal tract, and skin to urinary N tau-methylhistidine (MH) excretion were estimated during in vitro studies using the rat hemicorpus preparation. After 0.5 h of perfusion, MH release into the perfusate was linear for 3 h and averaged 29.8 nmol . h-1 . 100 g hemicorpus-1. In vivo, 24-h urinary MH excretion averaged 37.3 nmol . h-1 . 100 g body wt-1. The ratio of soft tissue to skin weight is equal (3.2:1) in the whole rat and in the hemicorpus. The gastrointestinal tract released 16.0 nmol . h-1 . 100 g body wt-1 or approximately 41% of the total urinary MH excretion. Preparations perfused with or without skin showed modest differences in the rate of MH release that were not statistically significant. Skeletal muscle contains 89.8% of total body MH content, whereas gastrointestinal tract and skin contain 3.8 and 6.4%, respectively. Gastrointestinal tract actomyosin turns over rapidly with a fractional catabolic rate of 24%/day versus 1.4%/day for skeletal muscle actomyosin.

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

2011 ◽  
Vol 9 (4) ◽  
pp. 319-326 ◽  
Author(s):  
Iva Miljkovic ◽  
Allison L. Kuipers ◽  
Candace M. Kammerer ◽  
Xiaojing Wang ◽  
Clareann H. Bunker ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
African Ancestry ◽  
Markers Of Inflammation ◽  
Muscle Adiposity

scholarly journals Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2169
Author(s):  
Kyung-Ah Cho ◽  
Da-Won Choi ◽  
Yu-Hee Kim ◽  
Jungwoo Kim ◽  
Kyung-Ha Ryu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Total Body Weight ◽  
Activin A ◽  
Dependent Manner ◽  
Muscle Loss ◽  
Total Body

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.

Wnt Pathway Inhibitor DKK1—A Potential Novel Biomarker for Ectopic Skeletal Muscle Adiposity

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2100-P
Author(s):  
HIRA ALI ◽  
JOSEPH M. ZMUDA ◽  
RYAN CVEJKUS ◽  
ERIN E. KERSHAW ◽  
ALLISON L. KUIPERS ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wnt Pathway ◽  
Muscle Adiposity

Abstract P363: Ectopic Adiposity is Associated With Abdominal Aorto-Illiac but Not Coronary Artery Calcification Independent of Total Body Adiposity in African Ancestry Men

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Allison L Kuipers ◽  
Joseph M Zmuda ◽  
J Jeffrey Carr ◽  
James G Terry ◽  
Sangeeta Nair ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Skeletal Muscle ◽  
Coronary Artery ◽  
Vascular Disease ◽  
Vascular Calcification ◽  
Body Fat ◽  
Coronary Artery Calcification ◽  
African Ancestry ◽  
Total Body Fat ◽  
Total Body

Objective: While ectopic adiposity is considered a risk factor for many chronic diseases, including cardiovascular disease, the extent to which this association is independent of total adiposity is yet to be established. Vascular calcification, which is associated with greater adiposity, is a subclinical marker of cardiovascular disease that may have varying etiology and clinical implications in different vascular beds. Therefore, our objective was to assess the potential independent associations of total, regional and ectopic adiposity measures with abdominal aorto-iliac calcification (AAC) and coronary artery calcification (CAC). Methods: Detailed health history, clinical exam, dual x-ray absorptiometry and computed tomography (CT) scans were obtained in 798 African ancestry men aged ≥40 years (mean(SD): 62.0(8.6)years) recruited without regard to health status from the Tobago Heart Health Study. Vascular calcification was measured by CT in the abdomen (AAC) and chest (CAC). Calcification was scored using the Agatston method and a score ≥10 was considered to be a prevalent calcification. Severity of calcification was modeled using continuous Agatston score in those with any calcification. Multivariable logistic and linear regression models were used to assess the cross-sectional association of adiposity measures with vascular calcification prevalence and severity. All models were adjusted for age, hypertension, diabetes, dyslipidemia, smoking, alcohol intake and sedentary lifestyle. In addition, models of ectopic adiposity (abdominal visceral adipose tissue, liver attenuation and calf skeletal muscle fat) were adjusted for total body fat. Results: AAC was present in 63% and CAC was present in 29% of men. After adjustment for traditional cardiovascular risk factors, 1SD greater total, trunk, or abdominal subcutaneous adiposity was associated with 1.3-1.5-fold increased odds of AAC (all p<0.05). After additional adjustment for total body fat, 1SD lower liver attenuation (indicative of greater liver adiposity) or 1SD greater skeletal muscle fat were each associated with a 1.2-1.3-fold increased odds of AAC. In fully adjusted models, only greater BMI or waist circumference was associated with increased odds of CAC (OR 1.2, p<0.05 for both). In fully adjusted linear models of calcification severity, no significant association was observed between any adiposity measure and AAC or CAC. Conclusions: Independent of total adiposity, measures of ectopic adiposity were associated with greater AAC, but not CAC, prevalence in African ancestry men. These results highlight potential differences in the adiposity-vascular disease relationship that may vary by ectopic fat depot and vascular bed location. Future vascular disease research should explore potential underlying biologic mechanisms for these findings.

Abstract MP047: Abdominal Skeletal Muscle Density is Significantly Associated With Selected Measures of Adiposity Associated Inflammation: the Multi-Ethnic Study of Atherosclerosis

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Rachel Van Hollebeke ◽  
Mary Cushman ◽  
Matthew A Allison
Keyword(s):  
Skeletal Muscle ◽  
Interleukin 6 ◽  
Subcutaneous Fat ◽  
Psoas Muscle ◽  
Abdominal Muscle ◽  
Muscle Area ◽  
Muscle Density ◽  
Ethnic Study ◽  
The Mean ◽  
Muscle Groups

Background: Excess adiposity is associated with higher levels of certain inflammatory markers that have been linked to cardiometabolic disease. Lean skeletal muscle is the largest regulator of glucose metabolism but few population-based studies have examined the associations between muscle and inflammation. Therefore, we studied the relationships between abdominal muscle mass [area] and density with selected measures of adiposity-associated inflammation. Methods: Nearly 2,000 subjects enrolled in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography (CT) of the abdomen and had venous fasting blood drawn concomitantly. The CT scans were interrogated for visceral and subcutaneous fat, as well as lean muscle areas and densities in the rectus abdominus, obliques, paraspinus and psoas muscle groups. We then categorized the muscle in locomotion (psoas) and stabilization groups (rectus, obliques and paraspinus). The blood samples were assayed for interleukin-6, resistin, C-reactive protein, and tumor necrosis factor - alpha. Multivariable linear regression was used to determine the independent associations between muscle area and density with each of the aforementioned adipokines. Results: The mean age was 64.7 years and 49% were female. Forty percent were non-Hispanic White, 26% were Hispanic/ Latino American, 21% were African American, 13% were Chinese American. The mean BMI was 28.0 kg/m 2 and 30% were obese (BMI > 30 kg/m 2 ). With adjustment for age, gender, race, dyslipidemia, diabetes, hypertension, eGFR, coronary artery calcium, physical activity, sedentary behavior, selected adipokines and both subcutaneous and visceral fat, a 1-SD increment in the mean densities for total abdominal muscle, total stabilization muscle and total locomotive muscle were each significantly associated with lower levels of interleukin-6 (-15%, -15% and -9%, p < 0.01 for all) and resistin (-0.11, -0.11 and -0.07 ng/mL, p < 0.02 for all), but not CRP or TNF-alpha. These associations remained significant after additional adjustment for muscle area in the corresponding muscle group. Conversely, the areas of the muscle variables were not independently associated with any of the adipokines, especially after adjustment for muscle density. There were no significant interactions between ethnicity and both muscle area and density for any of the adipokines. Conclusions: Higher densities of several muscle groups in the abdomen are significantly associated with lower interleukin-6 and resistin levels, independent of the muscle area in these groups. Techniques that either enhance or maintain muscle density levels may reduce the risk of cardiometabolic diseases linked to adverse levels of inflammation.

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