Leptin resistance develops spontaneously in mice during adult life in a tissue-specific manner. Consequences for hepatic steatosis

► Leptin resistance develops spontaneously in particular tissues during adult life. ► In the liver desensitization develops for the STAT3 but not for the Akt pathway. ► In adipose tissue desensitization concerns both STAT3 and Akt pathways. ► In the heart both STAT3 and Akt pathways keep full leptin responsiveness during adult life. ► The integrity of the STAT3 pathway is necessary to prevent hepatic steatosis.