leptin and 2-tetradecylglycidic-acid

Leptin may regulate peripheral fatty acid oxidation and invoke a feedback mechanism that affects leptin expression in adipocytes. The objective of this study, therefore, was to determine whether inhibiting systemic fatty acid oxidation at the level of carnitine palmitoyltransferase-1 (CPT1) affects leptin expression. To accomplish this objective, fed or overnight fasted rats were treated with 2-tetradecylglycidic acid (TDGA), a specific, irreversible CPT1 inhibitor, and acute changes in rat epididymal leptin expression and serum leptin content were measured using Northern, RT-PCR, and radioimmunoassay analyses. Overnight fasting decreased both epididymal leptin mRNA content and serum leptin. Treating overnight fasted rats with TDGA increased both their epididymal leptin mRNA and their serum leptin significantly in a time- and concentration-dependent manner. TDGA affected neither epididymal leptin mRNA nor serum leptin in fed rats where systemic fatty acid oxidation is low. These results support the conclusion that CPT1-linked fatty acid oxidation is a key modulator of leptin expression in fasting rats.

Topics: Animals; Carnitine O-Palmitoyltransferase; Enzyme Inhibitors; Epididymis; Epoxy Compounds; Fatty Acids; Gene Expression Regulation; Leptin; Male; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; RNA, Messenger

A reduction in the availability of oxidizable metabolic fuels inhibits reproduction. Forty-eight hours of metabolic fuel deprivation inhibits estrous behavior in ovariectomized, steroid-treated Syrian hamsters, but little is known about the time course of this inhibition. Likewise, refeeding reverses deprivation-induced suppression, but the rate of recovery has not been examined. In two experiments we determined 1) the rate at which estrous behavior declines in hamsters treated with metabolic inhibitors and 2) how rapidly sexual receptivity is restored when hamsters are refed after a 48-h fast. We also measured circulating levels of leptin and insulin in an attempt to determine their relationship to the inhibition and restoration of estrous behavior. More than 24 h of metabolic inhibitor administration were required to inhibit lordosis, whereas only 6 h of refeeding were sufficient to restore the display of sexual receptivity to normal levels. Neither plasma insulin nor leptin levels paralleled the changes in estrous behavior. We concluded that 1) suppression of estrous behavior occurs more slowly than recovery after a fast and 2) changes in circulating leptin and insulin probably do not have a critical role in these behavioral changes.

Topics: Animals; Cricetinae; Deoxyglucose; Epoxy Compounds; Estradiol; Estrus; Fatty Acids; Female; Food Deprivation; Hypoglycemic Agents; Insulin; Leptin; Mesocricetus; Ovariectomy; Posture; Progesterone; Sexual Behavior, Animal; Time Factors