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Glucose tolerance

BAT has beneficial effects on glucose tolerance

Findings show positive impact on body weight and metabolism
Dr Laurie J Goodyear

Brown adipose tissue (BAT) has beneficial effects on glucose tolerance, body weight and metabolism, according to findings in the forthcoming edition of the Journal of Clinical Investigation.

The researchers say that the findings could eventually lead to new methods of treating type 1 and 2 diabetes through the manipulation of the tissue.

Researchers from the Joslin Diabetes Center, Boston, wanted to determine whether BAT, which is one of two types of fatty tissue (the other being white adipose tissue) and is normally only found in its metabolically active state in newborns, is involved in glucose metabolism and uncover the mechanisms underlying its effects on metabolism and body weight.

They believe that the conditions are likely caused by an increase in the circulation of the signalling molecule interleukin 6 (IL-6), which can affect body temperature and energy mobilisation in muscle and fat tissue.

"This is the first study to demonstrate that an increase in BAT significantly increases levels of circulating IL-6. It suggests that an increase in BAT-derived IL-6 improves glucose metabolism throughout the body," said senior author Dr Laurie J Goodyear, head of the Section on Integrative Physiology and Metabolism. 

The study involved the transplantation of BAT from male donor mice into the visceral cavities of mice which were fed a standard or high-fat diet.

After living with the transplanted tissue for eight to twelve weeks, the mice fed a normal diet showed improved glucose tolerance, increased insulin sensitivity, lower body weights and decreased fat mass. Three control groups, which had a white adipose tissue transplant, a glass bead implant or surgery without transplantation, did not show any metabolic improvements.

“A remarkable finding from the current study was the ability of the BAT transplants to normalize glucose tolerance in the high-fat diet–fed mice”, the authors wrote.

As newborn children mature, BAT in their body begins to act more like ordinary white fat. However, the tissue transplanted into the mice continued to maintain the characteristics of lean, healthy BAT, counteracting the effects of feeding the mice a high-fat diet, and helped them improve their glucose metabolism.

The authors concluded that the link between increased IL-6 and improved glucose metabolism seen in the transplanted mice suggests that BAT should be further investigated as a potential treatment for metabolic disorders.

“This study provides further evidence that BAT is a very important metabolic organ and a potential treatment for obesity-related diseases such as diabetes, metabolic syndrome and insulin resistance," said lead author Dr Kristin I Stanford, a postdoctoral fellow in the Section on Integrative Physiology and Metabolism.

The researchers are currently examining other ways BAT may have beneficial metabolic effects and further investigating the functions of IL-6 and other BAT-derived hormones. They hope to develop new therapies by manipulating BAT to help type 1 and type 2 diabetics.

Study co-authors include: Roeland JW Middelbeek, Kristy L Townsend, Ding An, Eva B Nygaard, Kristen M. Hitchcox, Kathleen R Markan, Kazuhiro Nakano, Michael F  Hirshman, Yu-Hua Tseng, all of Joslin Diabetes Center.

The study was funded by the National Institutes of Health.

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