Hepatic leptin signalling and subdiaphragmatic vagal efferents are not required for leptin-induced increases of plasma IGF binding protein-2 (IGFBP-2) inob/obmice

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The fat-derived hormone leptin plays a crucial role in the maintenance of normal body weight and energy expenditure as well as in glucose homeostasis. Recently, it was reported that the liver-derived protein, insulin-like growth factor binding protein-2 (IGFBP-2), is responsible for at least some of the glucose-normalising effects of leptin. However, the exact mechanism by which leptin upregulates IGFBP-2 production is unknown. Since it is believed that circulating IGFBP-2 is predominantly derived from the liver and leptin has been shown to have both direct and indirect actions on the liver, we hypothesised that leptin signalling in hepatocytes or via brain-liver vagal efferents may mediate leptin control of IGFBP-2 production.


To address our hypothesis, we assessed leptin action on glucose homeostasis and plasma IGFBP-2 levels in both leptin-deficient ob/ob mice with a liver-specific loss of leptin signalling and ob/ob mice with a subdiaphragmatic vagotomy. We also examined whether restoring hepatic leptin signalling in leptin receptor-deficient db/db mice could increase plasma IGFBP-2 levels.


Continuous leptin administration increased plasma IGFBP-2 levels in a dose-dependent manner, in association with reduced plasma glucose and insulin levels. Interestingly, leptin was still able to increase plasma IGFBP-2 levels and improve glucose homeostasis in both ob/ob mouse models to the same extent as their littermate controls. Further, restoration of hepatic leptin signalling in db/db mice did not increase either hepatic or plasma IGFBP-2 levels.


Taken together, these data indicate that hepatic leptin signalling and subdiaphragmatic vagal inputs are not required for leptin upregulation of plasma IGFBP-2 nor blood glucose lowering in ob/ob mice.

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