Hypothalamic control of body fat mass by food intake: The key to understanding why obesity should be treated as a disease

Background: Hypothalamic centres have been recognized to play a central role in body weight regulation for nearly 70 years. Aims: In this review, we will explore the current undersanding of the role the hypothalamus plays in controlling food intake behaviours. Materials and methods: Review of relevant literature from PubMed searches and review article citations. Results: Beginning with autopsy studies showing destructive hypothalamic lesions in patients manifesting hyperphagia and rapid weight gain, followed by animal lesioning studies pinpointing adjacent hypothalamic sites as the 'satiety' centre and the 'feeding' centre of the brain, the neurocircuitry that governs our body weight is now understood to consist of a complex, interconnected network, including the hypothalamus and extending to cortical sites, reward centres and brainstem. Neurons in these sites receive afferent signals from the gastrointestinal tract and adipose tissue indicating food availability, calorie content, as well as body fat mass. Discussion: Integration of these complex signals leads to modulation of the two prime effector systems that defend a body fat mass set point: food intake and energy expenditure. Conclusion: Understanding the hypothalamic control of food intake forms the foundation for understanding and managing obesity as a chronic disease.