Brown adipose tissue is not associated with cachexia or increased mortality in a retrospective study of patients with cancer

Abstract

While brown fat is strongly associated with a constellation of cardiometabolic benefits in animal models and humans, it has also been tied to cancer cachexia. In humans, cancer-associated cachexia increases mortality, raising the possibility that brown fat in this context may be associated with increased cancer death. However, the effect of brown fat on cancer-associated cachexia and survival in humans remains unclear. Here, we retrospectively identify patients with and without brown fat on fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) scans obtained as part of routine cancer care and assemble a cohort to address these questions. We did not find an association between brown fat status and cachexia. Furthermore, we did not observe an association between brown fat and increased mortality in patients with cachexia. Our analyses controlled for confounding factors including age at cancer diagnosis, sex, body mass index, cancer site, cancer stage, outdoor temperature, comorbid conditions (heart failure, type 2 diabetes mellitus, coronary artery disease, hypertension, dyslipidemia, cerebrovascular disease), and beta-blocker use. Taken together, our results suggest that brown fat is not linked to cancer-associated cachexia and does not worsen overall survival in patients with cachexia.

Metabolic and histomorphological changes of adipose tissue in cachexia

“…These data were also confirmed in a cohort of gastrointestinal and genitourinary cancer with and without weight loss [15 ▪▪ ], indicating that mechanisms beyond thermogenesis induced by UCP1 may possibly contribute to the progression of cancer cachexia. Also, Eljalby et al [16] investigated in a large cohort of cancer patients the association between the brown fat by fluorodeoxyglucose ( 18 F-FDG) PET/CT, weight loss and mortality, observing that brown fat activation was not associated with cachexia nor with survival.…”

“…possibly contribute to the progression of cancer cachexia. Also, Eljalby et al [16] investigated in a large cohort of cancer patients the association between the brown fat by fluorodeoxyglucose ( 18 F-FDG) PET/CT, weight loss and mortality, observing that brown fat activation was not associated with cachexia nor with survival.…”

An update on the secretory functions of brown, white, and beige adipose tissue: Towards therapeutic applications

“…However, the complex relationship between BAT and cancer is not yet fully understood. A retrospective study of cancer patients found that BAT was not associated with cachexia or increased mortality [ 313 ]. In contrast, another study showed that exosomal miR-155 from gastric cancer cells induced cancer-associated cachexia by suppressing adipogenesis and promoting brown adipose differentiation through C/EPBβ [ 314 ].…”