Knowledge about how energy balance is regulated is imprtant for understanding animals' responses to rapid environmental change. Seals have the capacity to store large amounts of fat as blubber, and to allow those fat stores to vary dramatically during the year. There are 2 major reasons to study energy balance regulation in seals: firstly, they are sentinels of the health of the world's oceans and we need to better understand factors that influence their survival through impacts on energetics. Secondly, the study of seal fat dynamics could provide useful information the safe storage of large fat depots and rapid fat mobilisation useful for the management of human diabetes and obesity. However, studying fat regulation in seals isn't easy because experiments are challenging to run and often have to be relatively simple in design and involve a small sample size. We have borrowed an explant method from biomedical science and applied it in seals to better undertsand how blubber tissue responds to changes in glucose (a proxy for altered nutritional state) and altered hydrocortisone levels (a proxy for 'stress' exposure). We investigated glucose and fat metabolism and the expression of some key genes involved in fat tissue function. We showed that male grey seals break down fat at a higher rate than females do, which could explain why it takes males longer to lay down fat than females after the moult. Males and females also responded differently to high 'stress hormone' . We showed that high glucose levels stimulates the blubber to take up more glucose and produce more lactate and may alter sensitivity to stress. Seals have high levels of endogenous glucose production (EGP) and relatively high levels of circulating glucose, even when fasting. Our data led us to suggest that the high EGP might be a consequence of high lactate production by their big fat depots: turning it back into glucose can avoid lactic acidosis.