Brown adipose tissue and cancer progression

Chu, Katrina F.; Bos, Stijn A.; Gill, Corey M.; Torriani, Martin; Bredella, Miriam A.

doi:10.1007/s00256-019-03322-w

Cited by 26 publications

(15 citation statements)

References 33 publications

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“…It has been known that browning of WAT represents an early and systemic event in cachexia pathophysiology and contributes to increased thermogenesis. The high prevalence of BAT (80%) in CAC patients was observed and elevated BAT volume was associated with an increased possibility of tumour recurrence and tumour‐associated mortality 40,41 . The browning process of WAT is reflected by the increase in the number of beige adipocytes and the expression of UCP1 12,14 .…”

Section: Discussionmentioning

confidence: 99%

Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study

Luan

Zhang

et al. 2022

J cachexia sarcopenia muscle

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Background Cancer-associated cachexia (CAC) is a complex syndrome of progressive muscle wasting and adipose loss with metabolic dysfunction, severely increasing the morbidity and mortality risk in cancer patients. However, there are limited studies focused on the underlying mechanisms of the progression of CAC due to the complexity of this syndrome and the lack of preclinical models that mimics its stagewise progression. Methods We characterized the initiation and progression of CAC in transgenic female mice with ovarian tumours. We measured proposed CAC biomarkers (activin A, GDF15, IL-6, IL-1β, and TNF-α) in sera (n = 6) of this mouse model. The changes of activin A and GDF15 (n = 6) were correlated with the decline of bodyweight over time. Morphometry and signalling markers of muscle atrophy (n ≥ 6) and adipose tissue wasting (n ≥ 7) were assessed during CAC progression. Results Cancer-associated cachexia symptoms of the transgenic mice model used in this study mimic the progression of CAC seen in humans, including drastic body weight loss, skeletal muscle atrophy, and adipose tissue wasting. Serum levels of two cachexia biomarkers, activin A and GDF15, increased significantly during cachexia progression (76-folds and 10-folds, respectively). Overactivation of proteolytic activity was detected in skeletal muscle through up-regulating muscle-specific E3 ligases Atrogin-1 and Murf-1 (16-folds and 14-folds, respectively) with decreasing cross-sectional area of muscle fibres (P < 0.001). Muscle wasting mechanisms related with p-p38 MAPK, FOXO3, and p-AMPKα were highly activated in concurrence with an elevation in serum activin A. Dramatic fat loss was also observed in this mouse model with decreased fat mass (n ≥ 6) and white adipocytes sizes (n = 6) (P < 0.0001). The adipose tissue wasting was based on thermogenesis, supported by the up-regulation of uncoupling protein 1 (UCP1). Fibrosis in adipose tissue was also observed in concurrence with adipose tissue loss (n ≥ 13) (p < 0.0001). Conclusions Our novel preclinical CAC mouse model mimics human CAC phenotypes and serum biomarkers. The mouse model in this study showed proteolysis in muscle atrophy, browning in adipose tissue wasting, elevation of serum activin A and GDF15, and atrophy of pancreas and liver. This mouse line would be the best preclinical model to aid in clarifying molecular mediators of CAC and dissecting metabolic dysfunction and tissue atrophy during the progression of CAC.

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Section: Discussionmentioning

confidence: 99%

Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study

Luan

Zhang

et al. 2022

J cachexia sarcopenia muscle

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“…We found no association of BAT and lymphoma’s metabolic activity in our cohort. Former studies reported variable results on the role of cancer vitality in the regulation of BAT activity 31 , 33 , 36 . Also, BAT activity was not linked with the extent of weight change during the disease, in contrast to prior reports on cancer cachexia 35 .…”

Section: Discussionmentioning

confidence: 99%

Determinants of activity of brown adipose tissue in lymphoma patients

Brendle

Stefan

Grams

et al. 2020

Sci Rep

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The determinants of brown adipose tissue (BAT) activity are not yet known in detail but might serve as future therapeutic targets against obesity and the metabolic syndrome. We analyzed 235 datasets of lymphoma patients with two PET/CT examinations at different time points retrospectively. We assessed the anthropometric characteristics, features related to the metabolic syndrome, thyroid dysfunction, season of the PET/CT examination, weight change, prior cancer history, lymphoma subgroups, disease activity, and specific lymphoma-related therapies, and evaluated their association with BAT activity. We found BAT activity in 12% of all examinations, and the incidence of BAT activity after initially negative examinations was 10%. In multivariate regression analysis, the prevalence of BAT activity was associated with age, body mass index, sex, the season of the examination, diabetes mellitus, arterial hypertension, and medication on the beta-receptors. New BAT activity arose more often in patients without preceding lymphoma-related therapy. No specific medication was associated with BAT activity. In conclusion, this study confirms the potential connection of BAT with the metabolic syndrome. Preceding lymphoma-related therapy might have an inhibitory effect on the recruitment of BAT.

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“…In addition, significantly increased production of acute-phase proteins and cytokines is an energy-intensive process (15) and receptors for many cytokines are expressed in the feeding centres of the hypothalamus, therefore inflammation-mediated changes in the hypothalamic-pituitary axis result in illness behaviour (16) , including aberrations in appetite signalling and inhibition of orexigens resulting in poor oral intake (29) . Additional factors such as the browning of adipose tissue (30) , changes in carbohydrate metabolism (Cori cycle upregulation), changes in fat metabolism (fatty acid cycling), increased insulin resistance (31) and the demand for amino acids to drive the inflammatory response, results in increased muscle proteolysis and reductions in lean mass, which affects both skeletal muscle and muscular organs, such as the heart (15) . Furthermore, upregulation of the ubiquitin-proteasome pathway leads to increased muscle degradation (32) .…”

Section: Metabolic Derangements and Increased Energy Expenditurementioning

confidence: 99%

Impact of musculoskeletal degradation on cancer outcomes and strategies for management in clinical practice

Ryan

Sullivan

2020

Proc. Nutr. Soc.

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The prevalence of malnutrition in patients with cancer is one of the highest of all patient groups. Weight loss (WL) is a frequent manifestation of malnutrition in cancer and several large-scale studies have reported that involuntary WL affects 50–80% of patients with cancer, with the degree of WL dependent on tumour site, type and stage of disease. The study of body composition in oncology using computed tomography has unearthed the importance of both low muscle mass (sarcopenia) and low muscle attenuation as important prognostic indications of unfavourable outcomes including poorer tolerance to chemotherapy; significant deterioration in performance status and quality of life (QoL), poorer post-operative outcomes and shortened survival. While often hidden by excess fat and high BMI, muscle abnormalities are highly prevalent in patients with cancer (ranging from 10 to 90%). Early screening to identify individuals with sarcopenia and decreased muscle quality would allow for earlier multimodal interventions to attenuate adverse body compositional changes. Multimodal therapies (combining nutritional counselling, exercise and anti-inflammatory drugs) are currently the focus of randomised trials to examine if this approach can provide a sufficient stimulus to prevent or slow the cascade of tissue wasting and if this then impacts on outcomes in a positive manner. This review will focus on the aetiology of musculoskeletal degradation in cancer; the impact of sarcopenia on chemotherapy tolerance, post-operative complications, QoL and survival; and outline current strategies for attenuation of muscle loss in clinical practice.

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Brown adipose tissue and cancer progression

Cited by 26 publications

References 33 publications

Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study

Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study

Determinants of activity of brown adipose tissue in lymphoma patients

Impact of musculoskeletal degradation on cancer outcomes and strategies for management in clinical practice

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