The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice

Wiesenborn, Denise S.; Zhi, Xu; Do, Andrew; Gesing, Adam; Wang, Zhihui; Bartke, Andrzej; Altomare, Deborah A.; Masternak, Michal M.

doi:10.18632/aging.100700

Cited by 19 publications

(15 citation statements)

References 47 publications

(15 reference statements)

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“…This difference may be related to the fact that during the pre- and peripubertal period, male mice grow more rapidly than females and reach higher body weight at the age of 8 weeks (approximately 25 vs. 19 g). Our failure to detect a reduction in blood glucose levels in dwarf as compared to normal mice represents another difference from the results of previous studies [ 5 , 6 , 45 ]. The present lack of difference in blood glucose level can be potentially explained by the very young age of the animals.…”

Section: Discussioncontrasting

confidence: 99%

Thyroxine modifies the effects of growth hormone in Ames dwarf mice

Potts

Zhi

et al. 2015

Aging

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Ames dwarf (df/df) mice lack growth hormone (GH), thyroid stimulating hormone and prolactin. Treatment of juvenile df/df mice with GH alone stimulates somatic growth, reduces insulin sensitivity and shortens lifespan. Early‐life treatment with thyroxine (T4) alone produces modest growth stimulation but does not affect longevity. In this study, we examined the effects of treatment of juvenile Ames dwarf mice with a combination of GH + T4 and compared them to the effects of GH alone. Treatment of female and male dwarfs with GH + T4 between the ages of 2 and 8 weeks rescued somatic growth yet did not reduce lifespan to match normal controls, thus contrasting with the previously reported effects of GH alone. While the male dwarf GH + T4 treatment group had no significant effect on lifespan, the female dwarfs undergoing treatment showed a decrease in maximal longevity. Expression of genes related to GH and insulin signaling in the skeletal muscle and white adipose tissue (WAT) of female dwarfs was differentially affected by treatment with GH + T4 vs. GH alone. Differences in the effects of GH + T4 vs. GH alone on insulin target tissues may contribute to the differential effects of these treatments on longevity.

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Section: Discussioncontrasting

confidence: 99%

Thyroxine modifies the effects of growth hormone in Ames dwarf mice

Potts

Zhi

et al. 2015

Aging

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“…Indeed, our above observations in female mice are consistent with previous reports demonstrating that TZDs can increase circulating adiponectin without increasing Adipoq expression in WAT ( 23 , 24 ). However, other studies have reported a disparity between adiponectin expression at the transcript and protein level ( 32 , 33 ). Therefore, we next used fluorescence-based immunoblotting to detect and quantify adiponectin protein expression.…”

Section: Resultsmentioning

confidence: 90%

Increased Circulating Adiponectin in Response to Thiazolidinediones: Investigating the Role of Bone Marrow Adipose Tissue

et al. 2016

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BackgroundBone marrow adipose tissue (MAT) contributes to increased circulating adiponectin, an insulin-sensitizing hormone, during caloric restriction (CR), but whether this occurs in other contexts remains unknown. The antidiabetic thiazolidinediones (TZDs) also promote MAT expansion and hyperadiponectinemia, even without increasing adiponectin expression in white adipose tissue (WAT).ObjectivesTo test the hypothesis that MAT expansion contributes to TZD-associated hyperadiponectinemia, we investigated the effects of rosiglitazone, a prototypical TZD, in wild-type (WT) or Ocn-Wnt10b mice. The latter resist MAT expansion during CR, leading us to postulate that they would also resist this effect of rosiglitazone.DesignMale and female WT or Ocn-Wnt10b mice (C57BL/6J) were treated with or without rosiglitazone for 2, 4, or 8 weeks, up to 30 weeks of age. MAT content was assessed by osmium tetroxide staining and adipocyte marker expression. Circulating adiponectin was determined by ELISA.ResultsIn WT mice, rosiglitazone caused hyperadiponectinemia and MAT expansion. Compared to WT mice, Ocn-Wnt10b mice had significantly less MAT in distal tibiae and sometimes in proximal tibiae; however, interpretation was complicated by the leakage of osmium tetroxide from ruptures in some tibiae, highlighting an important technical consideration for osmium-based MAT analysis. Despite decreased MAT in Ocn-Wnt10b mice, circulating adiponectin was generally similar between WT and Ocn-Wnt10b mice; however, in females receiving rosiglitazone for 4 weeks, hyperadiponectinemia was significantly blunted in Ocn-Wnt10b compared to WT mice. Notably, this was also the only group in which tibial adiponectin expression was lower than in WT mice, suggesting a close association between MAT adiponectin production and circulating adiponectin. However, rosiglitazone significantly increased adiponectin protein expression in WAT, suggesting that WAT contributes to hyperadiponectinemia in this context. Finally, rosiglitazone upregulated uncoupling protein 1 in brown adipose tissue (BAT), but this protein was undetectable in tibiae, suggesting that MAT is unlikely to share thermogenic properties of BAT.ConclusionTZD-induced hyperadiponectinemia is closely associated with increased adiponectin production in MAT but is not prevented by the partial loss of MAT that occurs in Ocn-Wnt10b mice. Thus, more robust loss-of-MAT models are required for future studies to better establish MAT’s elusive functions, both on an endocrine level and beyond.

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“…As seen from our results, the increase in PI3K with DR may be due to increase in IGF-1 receptor possibly by an increase in the biological response to IGF-1 and hence, a subsequent increase in IRS-1. This increase in PI3K levels may be related to either increased local or paracrine secretion of IGF-1 [32]. In liver, the relative phosphorylation level of Akt protein increased in DR of 9-month-old mice while no change was seen in 21-month-old mice, as compared to AL-fed mice, which is correlated to PI3K level.…”

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confidence: 87%

Age- and Tissue-Dependent Modulation of IGF-1/PI3K/Akt Protein Expression by Dietary Restriction in Mice

Hadem

Sharma

2015

Horm Metab Res

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Insulin-like growth factor-1 (IGF-1), a key mediator of growth hormone action in mammals, plays an important role in the regulation of cellular and tissue functions. In the present investigation, the normal age-dependent and effect of dietary restriction on the expression levels of serum IGF-1, phosphotidylinositol 3-kinase (PI3K), and protein kinase B (PKB/Akt) in the liver, kidney and skeletal muscles of 1-, 9-, and 21-month-old female mice were ascertained using ELISA and Western blot analysis. Results showed that serum IGF-1 peaks at 9-month-old and decreases in older age. Dietary restriction (DR) decreases IGF-1 in both age groups. In liver, PI3K and relative amount of phosphorylated Akt (pAkt/Akt) showed an age-dependent correlated expression level as IGF-1 protein. In kidney and skeletal muscles, PI3K levels showed no changes with age. However, pAkt/Akt ratio increased in 9-month-old mice and decreased in 21-month-old mice. In liver, DR increased the level of PI3K and pAkt/Akt ratio in 9-month-old mice, but no significant change was seen in 21-month-old mice as compared to ad libitum-fed group. In kidney and skeletal muscles, DR mice showed an increase in PI3K level in both age groups while the pAkt/Akt ratio showed no change in 9-month-old mice, but exhibited a decrease in 21-month-old mice. These results indicate that there is a tissue-specific regulation of IGF-1/PI3K/Akt during normal aging and upon DR to help maintain the metabolic status of these tissues at those phases of animal's lifespan.

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The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice

Cited by 19 publications

References 47 publications

Thyroxine modifies the effects of growth hormone in Ames dwarf mice

Thyroxine modifies the effects of growth hormone in Ames dwarf mice

Increased Circulating Adiponectin in Response to Thiazolidinediones: Investigating the Role of Bone Marrow Adipose Tissue

Age- and Tissue-Dependent Modulation of IGF-1/PI3K/Akt Protein Expression by Dietary Restriction in Mice

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