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.