Feeding signals to the hungry mind.

Obesity, due to its associated co-morbidities, including type 2 diabetes and cardiovascular disease, is at the forefront of today's health care concerns. Our need for novel, multifaceted approaches to tackle the global increase of waistlines is urgent, and understanding the physiological processes underlying our vulnerability to weight gain is an important one of them. Evidence for considerable heritability of body weight indicates genetic influences in the susceptibility to our obesogenic environment. Here, we will focus on neurons in brain structures such as the hypothalamus, which sense the body's metabolic state and, through an intricate cascade of events, elicit an appropriate response. We will explore the use of genetically modified mouse models in the investigation of physiological functions of genes and pathways in neuronal regulation of metabolic balance. Use of these techniques allows us to make manipulations at the molecular level (e.g. in the neuronal metabolic sensing mechanism) and combine this with systems-level physiological analysis (e.g. body weight). Recent technological advances also enable the investigation of the contributions of genes to the co-morbidities of obesity, such as obesity-induced hypertension. Reviewing examples of improvements as well as large gaps in our knowledge, this lecture aims to incite interest in whole body physiological research.