Abstract
Ames dwarf (Prop1df, df/df) mice are characterized by growth hormone (GH), prolactin, and thyrotropin deficiency, remarkable extension of longevity and increased insulin sensitivity with low levels of fasting insulin and glucose. Plasma levels of anti-inflammatory adiponectin are increased in df/df mice, while pro-inflammatory IL-6 is decreased in plasma and epididymal fat. This represents an important shift in the balance between pro- and anti-inflammatory adipokines in adipose tissue, which was not exposed to GH signals during development or adult life. To determine the role of adipose tissue in the control of insulin signaling in these long-living mutants, we examined the effects of surgical removal of visceral (epididymal and perinephric) adipose tissue. Comparison of the results obtained in df/df mice and their normal (N) siblings indicated different effects of visceral fat removal (VFR) on insulin sensitivity and glucose tolerance. The analysis of the expression of genes related to insulin signaling indicated that VFR improved insulin action in skeletal muscle in N mice. Interestingly, this surgical intervention did not improve insulin signaling in df/df mice skeletal muscle but caused suppression of the signal in subcutaneous fat. We conclude that altered profile of adipokines secreted by visceral fat of Ames dwarf mice may act as a key contributor to increased insulin sensitivity and extended longevity of these animals.
Highlights
1.1 The Ames dwarf mouse Discovered in one of the mouse colonies at Iowa State University, Ames dwarf mice are homozygous for a spontaneous mutation in the Prophet of pituitary factor-1 (Prop1) gene whose product is responsible for pituitary development
Due to the loss-of-function mutation, the df/df mice are devoid of three anterior pituitary cell types – somatotrophs, lactotrophs and thyrotrophs – resulting in these mutants being deficient in the hormones secreted by these cells – growth hormone (GH), prolactin (PRL) and thyrotropin (TSH)
The weight of the fat pads removed from mice in the visceral fat removal (VFR) group was measured at the time of surgery
Summary
1.1 The Ames dwarf mouse Discovered in one of the mouse colonies at Iowa State University, Ames dwarf (df/df) mice are homozygous for a spontaneous mutation in the Prophet of pituitary factor-1 (Prop1) gene whose product is responsible for pituitary development. Due to the loss-of-function mutation, the df/df mice are devoid of three anterior pituitary cell types – somatotrophs, lactotrophs and thyrotrophs – resulting in these mutants being deficient in the hormones secreted by these cells – growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). Though indistinguishable from their siblings at birth, adult df/df mice are one-third the size of their normal (N) littermates. Due to GH deficiency, circulating levels of insulin-like growth factor 1 (IGF-1) are significantly low in the df/df mice These mice tend to get obese as they age. CR further extends the lifespan of df/df mice [6]
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