Some of the earliest changes in obesity are invisible – and they start in the brain. Of particular concern, many of the brain changes that accompany obesity bear striking resemblance to those that occur in brain injury. In this episode, we discuss how overeating can lead to inflammation and neuron dysfunction in specific parts of the brain that control appetite and energy regulation. We review the neuroscience of appetite regulation, energy expenditure, and body fat regulation. Topics include hypothalamic dysfunction of body fat regulation, leptin resistance, neuro-inflammation, and physical changes in the hypothalamus involving microglia (the immune cells of the brain). We also review what is known about avoiding and reversing these changes.