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The contribution of visceral fat to improved insulin signaling in Ames dwarf mice.

ABSTRACT: Ames dwarf (Prop1(df), 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.

SUBMITTER: Menon V

PROVIDER: S-EPMC4032618 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice.

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The hippocampus of Ames dwarf mice exhibits enhanced antioxidative defenses following kainic acid-induced oxidative stress.

Project description:IntroductionThe vulnerability of the hippocampus to the effects of aging has been found to be associated with a decline in growth hormone/insulin like growth factor-1 (GH/IGF-1), and an increase in oxidative stress. We have evidence that long-living GH-deficient Ames dwarf mice have enhanced antioxidant protection in the periphery but the protection in the central nervous system is less clear.Material and methodsIn the present study, we evaluated the antioxidative defense enzyme status in the hippocampus of Ames dwarf and wild type mice at 3, 12 and 24 months of age and examined the ability of each genotype to resist kainic acid-induced (KA) oxidative stress. An equiseizure concentration of KA was administered such that both genotypes responded with similar seizure scores and lipid peroxidation.ResultsWe found that GH-sufficient wild type mice showed an increase in oxidative stress as indicated by the reduced ratio of glutathione: glutathione disulfide following KA injection while this ratio was maintained in GH-deficient Ames dwarf mice. In addition, glutathione peroxidase activity (GPx) as well as GPx1 mRNA expression was enhanced in KA-injected Ames dwarf mice but decreased in wild type mice. There was no induction of Nrf-2 (an oxidative stress-induced transcription factor) gene expression in Ames dwarf mice following KA further suggesting maintenance of antioxidant defense in GH-deficiency under oxidative stress conditions.DiscussionTherefore, based on equiseizure administration of KA, Ames dwarf mice have an enhanced antioxidant defense capacity in the hippocampus similar to that observed in the periphery. This improved defense capability in the brain is likely due to increased GPx availability in Ames mice and may contribute to their enhanced longevity.

| S-EPMC6432800 | biostudies-literature

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