Editorials
Brown fat to help metabolic syndrome?
By Dr S Acharya, Chief Medical Editor
May 25, 2005 - 10:41:00 PM

Brown fat, so called because of its color in gross specimens is seen in neonates. The reason it looks brown is due to the presence of an abundance of mitochondria and vascular structures around it... Brown fat is thermogenic tissue. It produces large amounts of energy and heat to help neonates maintain body temperatures. By adulthood, the body fat is predominantly white fat. Precursors of brown fat are still present in adults and this is the basis for the study at the Joslin Diabetes Centre.
It is known that metabolic syndrome or syndrome X is a constellation of obesity, insulin resistance, hypertension and dyslipidaemia. It is associated with an increased risk of cardiovascular diseases. It was seen that the precursors of brown fat in adults were deficient in insulin receptor substrates (IRS) numbered 1 through 4, which are the first steps in insulin signaling inside the cell. Cell lines lacking IRS1 failed to develop into mature brown fat cells. Importantly, when they added the gene for IRS1 back into the knockout cells, the precursors recovered most of their ability to differentiate into brown fat cells.
In cells unable to form brown fat, the most over-expressed gene was for a protein called necdin. Until this study, necdin was a protein associated with nerve tissue and Prader-Willi syndrome, a neurodevelopmental disorder in children characterized by mental retardation, feeding problems and obesity. The Joslin researchers discovered that reducing the level of necdin is essential for precursor cells to give rise to brown fat cells. They have also found that a transcription factor called CREB is involved in this reduction
Presently though there is no consensus about when to assess a patient for metabolic syndrome or when to treat a patient with the syndrome, more physicians are recognizing the need to identify the syndrome early and start with life-style modifications. Drugs used for obesity itself in the UK are Orlistat and Sibutramine. Orlistat works by preventing fat absorption from the intestine, and therefore patients may suffer from side effects of oily leakage from rectum, flatulence, faecal urgency and faecal incontinence. Stibutramine, a centrally acting appetite suppressant, can be a problem to prescribe in a case of metabolic syndrome as its side effect is hypertension (one of the components of the syndrome).
�For now, diet, exercise and medication is the best approach for helping the body overcome insulin resistance and controlling type 2 diabetes,� said Dr C. Ronald Kahn, M.D., President of Joslin Diabetes Center, the Mary K. Iacocca Professor of Medicine at Harvard Medical School (HMS), and principal investigator of the study that appears in the June edition of the journal Nature Cell Biology. �But for people who are genetically predisposed to obesity, that approach often doesn�t work. As we learn more about the genesis of brown fat cells and the genes governing them, we may be able to target those genes with drugs or other agents to create powerful tools to fight obesity.�
With aspirin, statins and oral hypoglycaemic tablets available to combat the insulin resistance, hypercoaguability and dyslipidaemia in metabolic syndrome, guidelines on the use of medication for the proinflammatory state and obesity in metabolic syndrome would be welcome. Along with this the development of better anti-obesity drugs targeted at syndrome X would be essential. And the recent finding at the Joslin Diabetic Centre may be the answer.


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