Cold tolerance is impaired in SKO mice because of rapid depletion of hepatic glycogen. A and B, 12-week-old chow-fed Lox and SKO mice were exposed to 4 °C for 120 min (A) or for a shorter duration of 90 min (B) with ad libitum access to chow diet and water. Rectal temperatures were measured at the indicated time points with a YSI Inc. series precision thermometer. C, blood was collected by cardiac puncture following euthanasia, and blood glucose was measured by the glucose oxidase method. D, hepatic glycogen was measured by an enzyme-coupled spectrophotometric assay. E, 9-week-old Lox and SKO mice were fed a high fat diet for 3 weeks and subjected to a cold tolerance test. Detailed diet composition is available in the supplemental Methods. *, p < 0.05 versus Lox counterparts.