They can be leptin resistant

Feb 6, 2008 11:48 GMT  ·  By

Obesity goes far beyond the fatty tissues. A new research published in "Cell Metabolism" shows that the brain nuclei connected to appetite are wired differently in some obese people.

"The study was conducted in rats, not humans, and yet it could ultimately lead to novel obesity treatments. It is not just about drugs that modify short-term appetite, there may be drugs that stimulate development of the appropriate neural pathways. So, it is an exciting, but very early, time in this field," said Philip Smith, director of the Office of Obesity Research, at the National Institute of Diabetes and Digestive and Kidney Diseases.

Appetite and hunger have been so far connected to the arcuate nucleus in the hypothalamus (ARH). Some rat strains were resistant to obesity, others prone to it. The research team encountered fewer synapses in the arcuate nucleus of the individuals predisposed to obesity.

"Surprisingly, this deficiency developed very early in life, before the animals became obese, and appeared to extend into adulthood. Somehow, these animals are programmed to become obese. The obesity is hard-wired into the brain," said lead researcher Sebastien Bouret, an assistant professor of neuroscience at the University of Southern California.

Further investigation revealed that the neurons of the obesity-prone animals were less sensitive to leptin, a neurotransmitter controlling the development of the arcuate nucleus, but also involved in the hunger sensation and metabolic rate.

"It is important not to 'blame' the obese person or imply that he/she is responsible for being obese. Having said that, reasonable, healthy caloric restriction and a safe and sustainable program of physical activity can help limit weight gain and often bring about some degree of weight loss. In addition, healthy eating and regular exercise can reduce the complications of obesity such as type 2 diabetes and cardiovascular disease," said Dr. Barbara Kahn, chief of the Division of Endocrinology, Diabetes and Metabolism at Beth Israel Deaconess Medical Centre, in Boston.

"At the same time, not everyone can wear a size four. There is a certain aspect of genetics that sets somebody in a certain range of possible body weights, and then how that person lives his or her life will determine whether they are at the bottom or top of the range," she added.

It's clear now that both human and animal obesity is determined by genes and environmental factors. The studied rats grew obese when fed with a high-energy diet, but still on a normal diet, they were heavier than obesity-resistant individuals, but not having obese sizes.

"If drugs could be designed to influence the formation of neural circuits during development and targeted to at-risk pregnancies, there is a good likelihood we could have successful interventions that improve the health of the mother, and which have a major impact on disease risk for the infant, during pregnancy," said Smith.