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Obesity Wired In The Brain?

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A predisposition for obesity might be wired into the brain from the start, suggests a new study of rats.

Rats selectively bred to be prone to obesity show abnormalities in a part of the brain critical for appetite control, the researchers found. Specifically, the researchers show that the obese rats harbor defects in neurons of the arcuate nucleus (ARH) of the hypothalamus, which leaves their brains less responsive to the hunger-suppressing hormone leptin.

“The neurodevelopmental differences in these animals can be seen as early as the first week,” said Sebastien Bouret of the University of Southern California. “The results show that obesity can be wired into the brain from early life. The three-million-dollar question now is how to get around this problem.”

It is increasingly accepted that obesity results from a combination of genetic and environmental factors, the researchers said. Rodent models of obesity can provide valuable insights into the biological processes underlying the development of obesity in humans. The “diet-induced obese” (DIO) rats used in the current study are particularly suited to the task, according to Bouret, because their tendency to become overweight shares several features with human obesity, including the contribution of many genes.

A predisposition for obesity might be wired into the brain from the start, suggests a new study. (Credit: iStockphoto/Ekaterina Monakhova)

Previous studies had suggested that the brains of DIO rats are insensitive to leptin, the researchers added. Circulating leptin, produced by fat tissue, acts as a signal to the brain about the body’s energy status. Leptin is also critical for the initial development of ARH neurons.

In the new study, the researchers examined the obesity-prone rats for signs of abnormal brain development. They found that the animals’ brains had fewer neural projections from the ARH, a deficiency that persisted into adulthood. Those projections are needed to relay the leptin signal received by the ARH to other parts of the hypothalamus, Bouret said.

The researchers found further evidence that those changes in brain wiring stem from a reduced responsiveness of the brain to leptin’s action during development.

“It seems [in the case of these rats] that appetite and obesity are built into the brain,” Bouret said. While their condition might be ameliorated by exercising and eating right, he added, the findings suggest that the propensity to gain weight can’t be reversed.

But there is hope yet. It’s possible that treatments delivered during a critical early period of development might be capable of rewiring the brain, Bouret said.

Cell Metab. 2008 Feb;7(2):179-85.
Hypothalamic neural projections are permanently disrupted in diet-induced obese rats.
Neuroscience Program, The Saban Research Institute, Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA; Inserm, U837, Jean-Pierre Aubert Research Center, Université Lille 2, 59045 Lille, France.The arcuate nucleus of the hypothalamus (ARH) is a key component of hypothalamic pathways regulating energy balance, and leptin is required for normal development of ARH projections. Diet-induced obesity (DIO) has a polygenic mode of inheritance, and DIO individuals develop the metabolic syndrome when a moderate amount of fat is added to the diet. Here we demonstrate that rats selectively bred to develop DIO, which are known to be leptin resistant before they become obese, have defective ARH projections that persist into adulthood. Furthermore, the ability of leptin to activate intracellular signaling in ARH neurons in vivo and to promote ARH neurite outgrowth in vitro is significantly reduced in DIO neonates. Thus, animals that are genetically predisposed toward obesity display an abnormal organization of hypothalamic pathways involved in energy homeostasis that may be the result of diminished responsiveness of ARH neurons to the trophic actions of leptin during postnatal development.


Written by huehueteotl

February 7, 2008 at 9:52 am

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