Obesity is a global health issue. Treatment or prevention of obesity via lifestyle change remains elusive, particularly due to the lack of patient compliance and the subsequent weight regain following the cessation of dietary intervention. The hypothalamus is pivotal in regulating energy homeostasis by matching up energy intake and expenditure. Therefore, identifying novel mechanisms underlying these processes will provide new insights into the treatment of obesity. High-fat feeding has been reported to induce functional and structural impairment of the hypothalamus leading to leptin as well as ghrelin resistance. As a consequence regulation of energy homeostasis is disrupted.