Temporal Changes in Plasma Concentration of Leptin, IGF-1, Insulin and Metabolites Under Extended Fasting and Re-Feeding Conditions in Growing Lambs

BACKGROUND: A fall in plasma concentration of energy status related hormones (leptin, insulin-like growth factor-1 (IGF-1) and insulin) and body energy expenditure occurs in response to short term fasting. Nevertheless, the relations of the fasting-induced changes in energy related hormones and metabolites with fasting energy expenditure (FEE) under extended fasting condition have received little attention so far. OBJECTIVES: It is not clear how energy status related hormones coordinate to cope with feed deprivation under extended fasting time conditions and how quickly these hormones re-bound to fed-state values in response to re-feeding. Thus the objectives of this study were: 1) to determine the effects of extended fasting on plasma concentration of leptin, IGF-1, insulin, glucose, NEFA, 3-β-hydroxybutyrate (BOHB) and urea; and 2) to study the relations of energy status related hormones with FEE and substrate oxidations under extended fasting conditions. MATERIALS AND METHODS: Eighteen six-month-old growing lambs (9 females and 9 males) were fasted for three days. Blood samples were taken one hour before (-1H) and 48 and 72 hours after fasting (48H and 72H) and two hours after re-feeding (+2H) from jugular vein. During the last 22 hours of fasting, gas exchange (CO2 production and O2 consumption) were measured using an open-circuit indirect calorimeter. Respiratory quotient (RQ), FEE and relative proportions of oxidized protein, fat and carbohydrate were calculated. RESULTS: Plasma levels of leptin, insulin, IGF-1 and glucose decreased but NEFA and urea levels increased within 48H of fasting. Concentration of insulin significantly increased with extended fasting while leptin and IGF-1 levels remained constant. Glucose was the only blood variable that showed a quick re-bound within two hours after re-feeding. Leptin and IGF-1 showed significant positive relations with glucose and BOHB but negative relations with NEFA and Urea. Carbohydrate, fat and proteins contributed to 17%, 61% and 22% of FEE respectively in three-day-fasted lambs. FEE was negatively correlated with insulin and NEFA concentrations in plasma. CONCLUSIONS: Even though plasma levels of leptin and IGF-1 decreased and remained constant under extended fasting, neither leptin nor IGF1 re-bounded to fed-status values within two hours after re-feeding. Under extended fasting condition, firstly an insulin resistance develops and secondly, a fall in FEE through a switch from carbohydrate- to fat-based metabolism occurs and there is an evident negative correlation between FEE and plasma concentration of NEFA.