Insensitivity of well-conditioned mature XXXX to central administration of a leptin receptor antagonist.

@entity742 @entity1887 @entity1955 @entity6145 @entity701 @entity1718 @entity413 @entity1954
Ruminants remain productive during the @entity1887 or early lactation by evoking metabolic adaptations sparing available energy and nutrients (e.g. higher metabolic efficiency and induction of insulin resistance). A deficit in central leptin signaling triggers these adaptations in rodents but whether it does in ruminants remains unclear. To address this issue, five mature ewes were implanted with intracerebroventricular (ICV) cannula in the third ventricle. They were used in two experiments with an ovine leptin antagonist (OLA) when well-conditioned (average body condition score of 3.7 on a 5 point scale). The first experiment tested the ability of OLA to antagonize leptin under in vivo conditions. Ewes received continuous ICV infusion of artificial cerebrospinal fluid (aCSF), ovine leptin (4   g/h) or the combination of ovine leptin (4   g/h) and its mutant version OLA (40   g/h) for 48 h. Dry matter intake (DMI) was measured every day and blood samples were collected on the last day of infusion. ICV infusion of leptin reduced DMI by 24% (P < 0.05), and this effect was completely abolished by OLA co-infusion. A second experiment tested whether a reduction in endogenous leptin signaling in the brain triggers metabolic adaptations. This involved continuous ICV infusions of aCSF or OLA alone (40   g/h) for 4 consecutive days. The infusion of OLA did not alter voluntary DMI over the treatment period or on any individual day. OLA did not affect plasma variables indicative of insulin action ( @entity413 , non-esterified @entity1718 , insulin and the disposition of plasma @entity413 during an insulin tolerance test) or plasma @entity701 , but tended to reduce plasma @entity1954 and @entity1955 (P < 0.07). Overall, these data show that a reduction of central leptin signaling has little impact on insulin action in well-conditioned mature @entity742 . They also raise the possibility that reduced central leptin signaling plays a role in controlling @entity6145 production.
