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Obesity: is it all in your mind? – the brain’s control of appetite and body weight

Dr. Lora Heisler and Dr. Justin Rochford reflect on the interrelation of biology, behaviour and obesity.

Obesity represents a major medical and economic challenge of the 21st century. In the UK alone, nearly 1 in 4 individuals are obese, a rate that is predicted to rise annually. This is a concern because obesity substantially increases the risk of ill health, including diabetes, heart disease, and cancer, and reduces lifespan by an average of 9 years.

On a societal level, the health costs associated with obesity are in the billions each year and have the potential to cripple the UK’s National Health Service with a large percentage of the population requiring treatment for obesity and associated diseases. Currently, only one drug is approved for the clinical treatment of obesity. Given the prevalence of obesity worldwide and its health, societal, and economic implications, prevention and new treatments are a clinical imperative.

An understanding of the biological mechanisms regulating food consumption is therefore essential to both the successful prevention and treatment of obesity. The brain represents the master co-coordinator of energy homeostasis, employing a number of interwoven neurological circuits to continually appraise and respond to changes in nutritional state.

Over the past decade, the identification of individual genes whose disruption can cause obesity or lipodystrophy (an inability to appropriately develop fat) has been invaluable in deciphering and mapping principle pathways that regulate normal appetite, body weight, and the development of body fat.

In particular, the brain melanocortin network located in the brain region called the hypothalamus has been revealed to be a fundamental regulator of hunger / fullness and serves as a gateway for many of the body’s appetitive signals.  For example, key signals of appetite and body weight, such as the hormone leptin released from fat, influence the activity of the melanocortin pathway to stimulate or reduce appetite.  Furthermore, dysregulation of this pathway through disruptions in the brain melanocortin4 receptor is associated with the most common single-gene cause of human obesity, reflecting approximately 4% of the obese population.

The further identification of primary and critical cells in the brain regulating energy balance will facilitate the production of a more detailed roadmap of pathways through which hunger and fullness are mediated, which will ultimately have benefit for the prevention and treatment of global obesity.

Dr. Lora Heisler is a Wellcome Trust Senior Fellow in Basic Biomedical Sciences and a Lecturer in the Department of Pharmacology at the University of Cambridge.  Dr. Heisler’s career contributions to the field of obesity research were recently recognised by the receipt of the Lilly Scientific Achievement prize by the Obesity Society.

Dr. Justin Rochford is a Senior Research Associate and recipient of an MRC New Investigator Research Grant at the University of Cambridge Metabolic Research Laboratories.

About Lora Heisler

Lora Heisler
Dr. Lora Heisler is a Wellcome Trust Senior Fellow in Basic Biomedical Sciences and a Lecturer in the Department of Pharmacology at the University of Cambridge. Dr. Heisler’s career contributions to the field of obesity research were recently recognised by the receipt of the Lilly Scientific Achievement prize by the Obesity Society.

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