Dual Energy X-ray Absorptiometry (DEXA) as a longitudinal outcome measure of cancer-related muscle wasting in mice

Cole, Calvin; Beck, Christopher A.; Robinson, Deja; Ye, Jian; Mills, Bradley N.; Gerber, Scott A.; Schwarz, Edward M.; Linehan, David C.

doi:10.1371/journal.pone.0230695

Cited by 9 publications

(16 citation statements)

References 37 publications

(64 reference statements)

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“…Further research is needed to determine the continuous conditions of use for DXA. In recent years, DXA has been used to monitor the body compositions of model mice to learn more about lifestyle-related diseases [ 11 , 16 , 38 ]. In the future, if the usefulness and safety of DXA are proven in various disease model animals, it may be possible to conclusively show that DXA is a useful method for monitoring metabolic changes in mice.…”

Section: Discussionmentioning

confidence: 99%

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Noninvasive monitoring of muscle atrophy and bone metabolic disorders using dual-energy X-ray absorptiometry in diabetic mice

Kishi

Goto

TSURU³

et al. 2023

Exp. Anim.

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Tracking metabolic changes in skeletal muscle and bone using animal models of diabetes mellitus (DM) provides important insights for the management of DM complications. In this study, we aimed to establish a method for monitoring changes in body composition characteristics, such as fat mass, skeletal muscle mass (lean mass), bone mineral density, and bone mineral content, during DM progression using a dual-energy X-ray absorptiometry (DXA) system in a mouse model of streptozotocin (STZ)-induced type 1 DM. In the DM model, STZ administration resulted in increased blood glucose levels, increased water and food intake, and decreased body weight. Serum insulin levels were significantly decreased on day 30 of STZ administration. The DXA analysis revealed significant and persistent decreases in fat mass, lower limb skeletal muscle mass, and bone mineral content in DM mice. We measured tibialis anterior (TA) muscle weight and performed a quantitative analysis of tibial microstructure by micro-computed tomography imaging in DM mice. The TA muscle weight of DM mice was significantly lower than that of control mice. In addition, the trabecular bone volume fraction, trabecular thickness, trabecular number, and cortical thickness were significantly decreased in DM mice. Pearson’s product-moment correlation coefficient analysis showed a high correlation between the DXA-measured and actual body composition. In conclusion, longitudinal measurement of body composition changes using a DXA system may be useful for monitoring abnormalities in muscle and bone metabolism in animal models of metabolic diseases such as DM mice.

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Section: Discussionmentioning

confidence: 99%

“…DXA was performed in accordance with previous reports [ 16 , 17 ]. The body composition of each mouse was measured using a cone-beam flat-panel DXA detector (iNSiGHT VET DXA, Osteosys, Seoul, Korea).…”

Section: Methodsmentioning

confidence: 99%

Noninvasive monitoring of muscle atrophy and bone metabolic disorders using dual-energy X-ray absorptiometry in diabetic mice

Kishi

Goto

TSURU³

et al. 2023

Exp. Anim.

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“…In addition, a few studies define muscle wasting solely based on muscle function, while muscle mass was not taken into account. By measuring total lean body mass by DEXA, validity, as well as comparability, will be increased [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Pro-, Pre-, and Synbiotics on Muscle Wasting, a Systematic Review—Gut Permeability as Potential Treatment Target

et al. 2021

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Muscle wasting is a frequently observed, inflammation-driven condition in aging and disease, known as sarcopenia and cachexia. Current treatment strategies target the muscle directly and are often not able to reverse the process. Because a reduced gut function is related to systemic inflammation, this might be an indirect target to ameliorate muscle wasting, by administering pro-, pre-, and synbiotics. Therefore, this review aimed to study the potential of pro-, pre-, and synbiotics to treat muscle wasting and to elucidate which metabolites and mechanisms affect the organ crosstalk in cachexia. Overall, the literature shows that Lactobacillus species pluralis (spp.) and possibly other genera, such as Bifidobacterium, can ameliorate muscle wasting in mouse models. The beneficial effects of Lactobacillus spp. supplementation may be attributed to its potential to improve microbiome balance and to its reported capacity to reduce gut permeability. A subsequent literature search revealed that the reduction of a high gut permeability coincided with improved muscle mass or strength, which shows an association between gut permeability and muscle mass. A possible working mechanism is proposed, involving lactate, butyrate, and reduced inflammation in gut–brain–muscle crosstalk. Thus, reducing gut permeability via Lactobacillus spp. supplementation could be a potential treatment strategy for muscle wasting.

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“…We utilized the murine syngeneic-orthotopic model of PDAC-induced skeletal muscle wasting as described previously by our lab(10), and the overall study design is illustrated in Figure 1. With no previously defined sexual dimorphism in this model, only female C57BL/6J mice were utilized and were obtained from Jackson Laboratory (stock number 000664).…”

Section: Methodsmentioning

confidence: 99%

Validation of Dual Energy X-ray Absorptiometry for longitudinal quantification of tumor burden in a murine model of pancreatic ductal adenocarcinoma

Sechrist,

Lee,

Schwarz

et al. 2023

Preprint

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Noninvasive imaging is central to preclinical, in vivo models of pancreatic ductal adenocarcinoma (PDAC). While bioluminescent imaging (BLI) is a gold standard, its signal is dependent on the metabolic activity of tumor cells. In contrast, dual energy X-ray absorptiometry (DEXA) is a direct measure of body composition. Thus, we aimed to assess its potential for longitudinal quantification of tumor burden versus BLI. We utilized the KCKO murine model of PDAC and subjected tumor-bearing (n = 20) and non-tumor control (NTC) (n = 10) animals to weekly BLI and DEXA measurements for up to 10 weeks. While BLI detected tumors at 1-week, it failed to detect tumor growth, displayed a decreasing trend overtime (slope = -9.0x108; p = 0.0028), and terminal signal did not correlate with ex vivo tumor mass (r = 0.01853; p = 0.6286). In contrast, DEXA did not detect elevated changes in abdominal cavity lean mass until week 2 post inoculation and tumors were not visible until week 3, but successfully quantified a tumor growth trend (slope = 0.7322; p<0.0001), and strongly correlated with final tumor mass (r = 0.9351; p<0.0001). These findings support the use of BLI for initial tumor engraftment and persistence but demonstrate the superiority of DEXA for longitudinal tumor burden studies. As tumor detection by DEXA is not restricted to luciferase expressing models, future studies to assess its value in various cancer models and as an in vivo outcome measure of treatment efficacy are warranted.

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Dual Energy X-ray Absorptiometry (DEXA) as a longitudinal outcome measure of cancer-related muscle wasting in mice

Abstract: ConclusionsDEXA is a longitudinal outcome measure of lean mass in mice. The KCKO syngeneic model is a bona fide model of PDAC associated SMW that can be quantified with longitudinal DEXA.

Cited by 9 publications

References 37 publications

Noninvasive monitoring of muscle atrophy and bone metabolic disorders using dual-energy X-ray absorptiometry in diabetic mice

Noninvasive monitoring of muscle atrophy and bone metabolic disorders using dual-energy X-ray absorptiometry in diabetic mice

The Effects of Pro-, Pre-, and Synbiotics on Muscle Wasting, a Systematic Review—Gut Permeability as Potential Treatment Target

Validation of Dual Energy X-ray Absorptiometry for longitudinal quantification of tumor burden in a murine model of pancreatic ductal adenocarcinoma

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