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Cold-activated fat cells help slow tumor growth

Researchers found that brown fat activated by cold temperatures can slow the growth of cancerous tumors.

Image Credit: Photo by Aaron Burden on Unsplash

A recent study led by researchers from Sweden and China have found that a type of fat, called brown fat, has the ability to reduce the growth of cancerous tumors. Scientists have shown that white fat, also known as white adipose tissue, can turn into brown fat, also known as brown adipose tissue, when it is subjected to cold temperatures. 

In cold conditions, brown fat inside our bodies becomes activated and uses glucose to generate heat. Cancer cells also require a lot of glucose – more than healthy cells – due to a process called the Warburg effect. The Warburg effect is a process by which cells increase their intake and breakdown of glucose in the presence of oxygen, or aerobically

This process normally occurs without oxygen present, or anaerobically. But in cancer cells, glucose uptake and breakdown occurs 10-100 times faster aerobically, aiding in their growth. Since brown fat also uses a lot of glucose, researchers hypothesized it could compete with cancer cells for glucose, and thereby slow tumor growth.

In particular, these researchers tested how cold acclimation and brown fat affected tumor growth in mice with colorectal cancer. To do so, they transplanted cancerous tissues into mice under temperatures of 4ºC, or 39ºF, and compared them with mice kept at 30ºC, or 86ºF. 

They found tumor growth in the mice was inhibited up to 80% under cold conditions compared to warm conditions, by the activation of brown fat. However, after they surgically removed the brown fat from the mice, the tumors continued to grow even under cold conditions. They interpreted this finding as indicating the brown fat was vital for suppressing tumor growth.

The scientists also examined a protein that allows brown fat to take in glucose and generate heat, called Ucp1. The authors deleted the Ucp1 gene from a line of mice, and found the tumor suppressive effect of brown fat in the cold was abolished in mice without this gene. In these mice, the tumors grew regardless of the temperature. In fact, their tumor sizes and amount of activated brown fat at 4ºC were not significantly different from those at 30ºC. 

The authors suspected glucose uptake could explain how brown fat acted as a tumor suppressor. To test this hypothesis, they monitored a marker for tissue uptake of glucose, called F-FDG. Using PET-CT scans, they found cold exposure activated this marker along the spine of the mice, where brown fat is mostly located. 

The team noted F-FDG mainly accumulated in the mice’s tumor tissues at 30ºC. But at 4ºC, more F-FDG accumulated in the brown fat along the spinal region, and less F-FDG accumulated in the tumors. They interpreted this result as indicating the glucose went into brown fat under cold conditions, and into the tumors under warm conditions. 

The researchers also performed two similar tests on humans, one on healthy people and one on a cancer patient. In the first test, the healthy patients remained at 16ºC, or 60ºF, for 2 to 6 hours per day. In the second test, the cancer patient remained at 22ºC, or 70ºF. The researchers emphasized the participants wore very light clothing and were placed in tolerable coldness for these trials. 

The researchers imaged the patients with CT scans and found brown fat was activated in both tests. Using the F-FDG marker, they found less glucose uptake in the tumor of the cancer patient, even at 22ºC. They also detected glucose uptake in the brown fat of this patient. When the patient was exposed to 28ºC, or 82ºF, less brown fat was activated and the tumor proceeded to grow.  

The authors concluded that activating brown fat with cold temperatures interfered with the tumor cells’ ability to grow by rapidly taking in glucose via the Warburg effect. By providing an alternate path for glucose to be absorbed into the body, the tumor cells are ultimately cut off from their supply. The authors suggested therapeutic agents that activate brown fat could be further developed to provide a long-term treatment for slowing tumor growth. 

Study Information

Original study: Brown-fat-mediated tumor suppression by cold-altered global metabolism

Study was published on: August 3, 2022

Study author(s): Takahiro Seki, Yunlong Yang, Xiaoting Sun, Sharon Lim, Sisi Xie, Ziheng Guo, Wenjing Xiong, Masashi Kuroda, Hiroshi Sakaue, Kayoko Hosaka, Xu Jing, Masahito Yoshihara, Lili Qu, Xin Li, Yuguo Chen, Yihai Cao

The study was done at: Karolinska Institutet (Sweden), Fudan University (China), Wenzhou Medical University (China), Fujian Medical University (China), West China Hospital (China), Qilu Hospital of Shandong University (China), Tokushima University Graduate School (Japan), People’s Hospital of Hangzhou Medical College (China)

The study was funded by: National Program on Key Research, Scandinavia-Japan Sasakawa Foundation, Karolinska Institute Foundation, Japan Society for the Promotion of Science, European Research Council, Swedish Research Council, Swedish Cancer Foundation, Swedish Children’s Cancer Foundation, Strategic Research Areas (SFO) –Stem Cell and Regenerative Medicine Foundation, Torsten Soderbergs Foundation, Maud and Birger Gustavsson Foundation, NOVO Nordisk Foundation, Knut and Alice Wallenberg’s Foundation

Raw data availability: Not available

Featured image credit: Photo by Aaron Burden on Unsplash

This summary was edited by: Ruby Costigan