Brown Fat May Affect Cancer Progression

Tuesday, Nov. 27, 2018

Brown adipose tissue (BAT) activity is greater in patients with active malignancy than in comparable BAT positive patients without active malignancy, according to a study presented on Monday.



This suggests that BAT — also referred to as "brown fat" — plays a role in cancer progression, said Miriam Bredella, MD, professor of radiology, Harvard Medical School.

Adipose tissue is known to influence the development and progression of different cancers. In her presentation Dr. Bredella explained that white adipose tissue stores energy and becomes "dysfunctional" in obesity, increasing the risk of developing metabolic disease and cancer. BAT is metabolically active and is characterized by high mitochondrial content and high vascularity.

"Active brown adipose tissue refers to BAT that is visible on FDG-PET because it is metabolically active and takes up glucose," Dr. Bredella said. "Some studies suggest that BAT can also be 'non-active' or 'cold' on FDG-PET and does not take up glucose."

The purposed of this study was to determine the role BAT plays in cancer activity.

The study group included 142 patients, 121 of whom were female, with a mean age of 49 years. Those patients had lymphoma (38), lung cancer (23), gastrointestinal cancer (21), breast cancer (18), melanoma (12), genitourinary cancer (11), thyroid cancer (10), and sarcoma/carcinoma of unknown origin (9).

The patients underwent 18F-FDG PET/CT for staging or surveillance of malignant neoplasms and were BAT-positive on PET/CT. The researchers assessed BAT volume by PET/CT, and abdominal fat and paraspinous muscle cross sectional areas (CSA) by CT, and groups with and without active malignant disease on PET/CT were compared.

The groups were similar in age and BMI, and abdominal and muscle CSA. Patients with active malignant disease on PET/CT had higher BAT volume compared to patients without active malignancy (24±6 vs 12±2 cm3, p=0.009). In patients without active malignancy, BAT volume was associated with BMI and abdominal fat CSA (r= 0.56 to 0.58, p<0.0001) while there were no such associations in patients with active malignancy (p>0.2). No associations between BAT volume and age or muscle CSA were found (p>0.1).

What are the mechanisms through which brown fat plays a role in the development or progression of cancer?

"Brown fat is very vascular," Dr. Bredella said. "And studies have shown increased expression of the protein CD31 (a marker of angiogenesis in brown adipose tissue), which may lead to cancer development by favoring tumor growth through increased vascularity."

Dr. Bredella also pointed out that studies have been performed in animal models where different cancer types were implanted into brown fat, leading to accelerated tumor growth, increased neovascularization, increased blood perfusion and decreased hypoxia.

"Our preliminary investigation suggests a possible role of BAT in cancer activity and associated metabolic disturbances, but prospective longitudinal studies are necessary to assess the effects of BAT on cancer activity and progression," Dr. Bredella said. "In the future, modulation of BAT may play a role in cancer therapy."

Dr. Bredella received a 2018 Society of Skeletal Radiology Paper Award for this study.