The endocannabinoid system regulates energy homeostasis and is linked to obesity development, but the exact dynamic and brain regulation, during obesity progression, is incompletely understood. This study is the first of its kind to look at the time course of responses in two normal, inborn endocannabinoids, 2-AG and Anandamide, in male and female mice during diet-induced obesity. They also explore changes in brown adipose tissue, which help to control body heat and weight. They look at changes in blood levels associated with high-fat diets and over-feeding. Interestingly, they found that changes are sexually dimorphic: hypothalamic cannabinoid levels were higher in female mice, who became obese at later time points than males. This study contributes to the understanding of hypothalamic regulation of obesity, which currently affects nearly 1/3 of the world’s population. http://bit.ly/2QCrA4M