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Brown fat data expand, show promise in treatment of obesity
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PHOENIX — Brown fat tissue may be a promising treatment for obesity if researchers can harness the substance’s ability to burn extra lipids stored in white fat cells, according to Aaron Cypess, MD, PhD, of the Joslin Diabetes Center and Beth Israel Deaconess Medical Center.
Cypess spoke at a press conference here about a translational research project that has garnered attention recently due to studies published in Nature Medicine.
Role of brown fat
In the Nature Medicine study, Cypess and colleagues demonstrated that in humans, neck fat has a predominantly brown developmental lineage. During his talk, Cypess said this is significant because even at baseline, this type of brown adipose tissue (BAT) in a mouse can consume 800 picomole per minute of oxygen with the ability alter energy balance, glucose and triglyceride levels.
“The most enriched brown fat we saw in humans can consume nearly half of that – a very high amount – even at baseline. In contrast, the subcutaneous fat in these people had a much lower energy consumption rate.”
Additionally, the researchers were able to grow brown fat cells from precursor cells collected from people and demonstrated that these cells could then be stimulated to be active.
“In that case, one now has the opportunity to make brown fat cell lines from humans and screen libraries to see which drugs work to activate the tissue,” he said.
Future use of BAT
Cypess explained that BAT is excellent for energy expenditure, noting that 50 grams alone mayburn off 100 to 300 kcals per day and even more if maximally stimulated. Brown fat also has a significant role in cold-induced or non-shivering thermogenesis and is involved in diet-induced thermogenesis.
“So, with the discovery of human BAT, there is an organ in our bodies that is designed specifically to burn off calories in a safe and controlled manner.”
This brown fat can now be measured using noninvasive PET-CT, though additional diagnostic tools will be available, he said.
Currently, no pharmacologic brown fat activators have been identified, though mild cold exposure is effective at stimulating brown fat in prospective studies. Finally, while its energy expenditure has great therapeutic potential, the extent of this potential remains to be determined, he said.
However, in an interview with Endocrine Today, Cypess said he and colleagues are looking at beta 3 adrenergic receptor agonists, which are known to successfully stimulate BAT in tissue culture and rodents.
“The challenge has been, so far, to identify any of these compounds that then also work in humans; that has been something that’s been sought after by several pharmaceutical companies over the past 2 decades or more, and that’s one area that will receive increased attention,” he said. “But there’s a whole host, perhaps 20 peptide hormones and other kinds of compounds, that have been shown to increase brown fat mass and activity in rodent models. Now with the ability to have cell lines that can be studied in vitro, we can test all of these and see [which] have promise, which are most potent and [which] we could use in a human model.”
For more information:
Cypess A.M. United colors of fat metabolism … White, brown and beige. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.
Disclosure: Cypess and colleagues have received grant support from NIH, the Eli Lilly Foundation and Chugai Pharma, Ltd.