Limbic Effects On Physical Activity And Obesity

sharma-obesity-running-mouseThe amygdala is a part of the so-called limbic system that performs a primary role in the processing of memory, decision-making, and emotional reactions. The amygdala has also been implicated in a variety of mental health problems including anxiety, binge drinking and post-traumatic stress syndrome.

A study by Xu and colleagues, published in the Journal of Clinical Investigation now shows that in mice, activity of the estrogen receptor–α (ERα) in the medial amygdala may have a profound influence on the development of obesity – an effect, which appears to me largely mediated through effects on physical activity.

Building on previous work showing that ERα activity in the brain prevents obesity in both males and female rats, the researchers used a series of complex experiments to demonstrate that specific deletion of the ERα gene from SIM1 neurons, which are highly expressed in the medial amygdala, cause a marked decrease in physical activity and weight gain in both male and female mice fed with regular chow, without any increase in food intake. In addition, this deletion caused increased susceptibility to diet-induced obesity in males but not in females.

Deletion of the ERα receptor also blunted the body weight-lowering effects of a glucagon-like peptide-1-estrogen (GLP-1-estrogen) conjugate.

In contrast, over-expression or stimulation of SIM1 neurons increased physical activity in mice and protected them from diet-induced obesity.

These findings point to a novel mechanism of neuronal control of physical activity, which in turn appears to have important effects on the susceptibility to weight gain.

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