Brown Adipose T issue ( BAT )

1. Brown Adipose Tissue (BAT) AKABrown Fat

2. Brown Fat • One of two types of fat or adipose tissue (the other being white adipose tissue) found in mammals. • It is especially abundant in newborns and in hibernating mammals.[1] • Its primary function is to generate body heat in animals or newborns that do not shiver.

3. Brown Fat • In contrast to white adipocytes (fat cells), which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a much higher number of (iron containing) mitochondria, which make it brown.[2] • Brown fat also contains more capillaries than white fat, since it has a greater need for oxygen than most tissues

4. PET/CT Scan of Brown Fat

5. Presence in Adults • It was believed that after infants grow up, most of the mitochondria (which are responsible for the brown color) in brown adipose tissue disappear, and the tissue becomes similar in function and appearance to white fat. • However, more recent research has shown that brown fat is related not to white fat, but to skeletal muscle.[3][4][5] • Further, recent studies using Positron Emission Tomography scanning of adult humans have shown that it is still present in adults in the upper chest and neck.

6. Presence in Adults • The remaining deposits become more visible (increasing tracer uptake, that is, more metabolically active) with cold exposure, and less visible if an adrenergic beta blocker is given before the scan. • The recent study could lead to a new method of weight loss, since brown fat takes calories from normal fat and burns it.

7. Presence in Adults • Scientists were able to stimulate brown fat growth in mice, but human trials have not yet begun.[6][7] • In rare cases, brown fat continues to grow, rather than involuting; this leads to a tumour known as a hibernoma.

8. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • ScienceDaily (Aug. 2, 2012) — Columbia University Medical Center (CUMC) researchers have identified a mechanism that can give energy-storing white fat some of the beneficial characteristics of energy-burning brown fat. • The findings, based on studies of mice and of human fat tissue, could lead to new strategies for treating obesity and type 2 diabetes. • The study was published August 2 in the online edition of the journal Cell.

9. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • Newborns have a relative abundance of brown fat, as protection against exposure to cold temperatures. • In adults, however, almost all excess energy is stored as white fat.

10. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • "Turning white fat into brown fat is an appealing therapeutic approach to staunching the obesity epidemic, but it has been difficult to do so in a safe and effective way," said study leader Domenico Accili, MD, professor of Medicine and the Russell Berrie Foundation Professor at CUMC. • White fat can be "browned" with a class of drugs called thiazolidazines (TZDs), which increase the body's sensitivity to insulin.

11. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • However, TZDs have many adverse effects -- including liver toxicity, bone loss, and, ironically, weight gain -- which have limited the use of these drugs. • The current study was undertaken to learn more about the function of TZDs, with the ultimate goal of developing better ways to promote the browning of white fat.

12. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • Scientists have known that TZDs promote the browning of white fat by activating a cell receptor called peroxisome proliferator-activated receptor-gamma (ppar-gamma), but the exact mechanism was not clear. • To learn more, Dr. Accili and his colleagues studied a group of enzymes called sirtuins, which are thought to affect various biological processes, including metabolism.

13. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • The researchers had previously shown in mice that when sirtuin activity increases, so does metabolic activity. • In the present study, they found that sirtuins boost metabolism by promoting the browning of white fat.

14. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • "When we sought to identify how sirtuins promote browning, we observed many similarities between the effect of sirtuins and that of TZDs," said lead author Li Qiang, PhD, associate research scientist in Medicine at CUMC.

15. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • Sirtuins work by severing the chemical bonds between acetyl groups and proteins, a process known as deacetylation. • "So the next question was whether sirtuins remove acetyl groups from ppar-gamma and, indeed, that was what we found," said Dr. Qiang.

16. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • To confirm that the deacetylation of ppar-gamma is crucial to the browning of fat, the researchers created a mutant version of ppar-gamma, in effect mimicking the actions of sirtuins. • The mutation promoted the development of brown fat-like qualities in white fat.

17. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • "Our findings have two important implications," said Dr. Accili. • "First, they suggest that TZDs may not be so bad -- if you can find a way to tweak their activity. • Second, one way to tweak their activity is by using sirtuin agonists -- that is, drugs that promote sirtuin activity."

18. Turning White Fat Into Energy-Burning Brown Fat: Hope for New Obesity and Diabetes Treatments • "The truth is, making sirtuin agonists has proved to be a real bear -- more promise than fact," he continued. • "But now, for the first time, we have a biomarker for good sirtuin activity: the deacetylation of ppar-gamma. • In other words, any substance that deacetylatesppar-gamma should in turn promote the browning of white fat and have a beneficial metabolic effect." • Dr. Accili's paper is titled, "Brown Remodeling of White Adipose Tissue by SirT1-Dependent Deacetylation of Ppar-gamma." The other contributors are NingKon (CUMC), Wenhui Zhao (CUMC), Sangkyu Lee (University of Chicago, Chicago, Illinois), Yiying Zhang (CUMC), Michael Rosenbaum (CUMC), Yingming Zhao (University of Chicago), Wei Gu (CUMC), and Stephen R. Farmer (Boston University School of Medicine, Boston, Mass.)