Thyroid hormones (TH) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating thyroid hormones that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity suggesting that in mammals naturally adapted to prolonged fasting TH are necessary to support metabolism. However, the functional relevance of this physiological paradox has remained largely unexplored especially as it relates to the regulation of lipids. To address the hypothesis that thyroid stimulating hormone (TSH)-mediated increase in TH contributes to lipid metabolism, we infused early- and late-fasted pups with TSH and measured several key genes in adipose and muscle, and plasma hormones associated with the regulation of lipid metabolism. TSH infusion increased the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) over 6.5-fold at 60 minutes in muscle, and the expression of uncoupling protein 2 (UCP2) over 27-fold during the early fast at 60 minutes, in adipose. Additionally, during the late fast the protein content of adipose CD36 increased 1.1-fold and plasma NEFA concentrations increased 25% at 120 mins, with NEFA levels returning to baseline after 24 hrs. Here we show that the TSH-induced increases in TH in fasting pups are functional and likely contribute to the maintenance of a lipid-based metabolism.