Endocrine Abstracts

An increasing number of factors exclusively or predominantly expressed in and released from adipocytes have been identified and shown to have important functions for energy metabolism. Adiponectin is one of these factors that have been implicated in the control of systemic insulin sensitivity. We have recently shown that pharmacological elevation of adiponectin levels results in a transient decrease of plasma glucose levels. This is primarily achieved through a repression of hepatic glucose output as a consequence of improved insulin sensitivity.
Adiponectin in serum is subject to complex hormonal regulation and displays sexually dimorphic levels with respect to absolute amounts circulating as well as oligomerization state of the adiponectin complex.
We have generated transgenic mouse models that overexpress adiponectin at levels three- to fourfold above normal levels. These mice are not lipodystrophic and have normal plasma glucose, insulin and lipid levels in the fasting state. However, they are more insulin sensitive as judged by oral glucose tolerance tests and clamp studies, clear oral lipid loads from serum much more rapidly than their wildtype counterparts and less prone to diet-induced insulin resistance. The primary site of improved insulin sensitivity is at the level of the hepatocyte. Furthermore, overexpression of adiponectin leads to a pronounced hyperproliferation of the interscapular fat pad as well as (at late age) periorbital adipose tissue. These studies in transgenic mice corroborate previous acute pharmacological studies and implicate the protein in carbohydrate and lipid metabolism.