Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice

Reynolds, Thomas H.; Merrell, Erin; Cinquino, Nicholas; Gaugler, Megan; Ng, Lily

doi:10.1152/ajpregu.00358.2012

Cited by 11 publications

(7 citation statements)

References 32 publications

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“…In vivo insulin action was determined by conducting IAGT testing, a procedure that has been to detect diet-induced insulin resistance at more physiological relevant blood glucose levels than insulin tolerance testing [ 15 , 22 ]. In the fasted basal state, blood glucose values were higher in the HFD-SED mice compared to all other groups (HFD-SED: 190.1 ± 8.4 vs. HFD-WR: 142 ± 9.1 vs. LFD-SED: 122.1 ± 4.6 vs. LFD-WR: 147.9 ± 18.8).…”

Section: Resultsmentioning

confidence: 99%

Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice

et al. 2015

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Cidea and Cidec play an important role in regulating triglyceride storage in liver and adipose tissue. It is not known if the Cidea and Cidec genes respond to a high fat diet (HFD) or exercise training, two interventions that alter lipid storage. The purpose of the present study was to determine the effect of a HFD and voluntary wheel running (WR) on Cidea and Cidec mRNA and protein expression in adipose tissue and liver of mice. A HFD promoted a significant increase in Cidea and Cidec mRNA levels in adipose tissue and liver. The increase in Cidea and Cidec mRNAs in adipose tissue and liver in response to a HFD was prevented by WR. Similar to the changes in Cidea mRNA, Cidea protein levels in adipose tissue significantly increased in response to a HFD, a process that was, again, prevented by WR. However, in adipose tissue the changes in Cidec mRNA did not correspond to the changes in Cidec protein levels, as a HFD decreased Cidec protein abundance. Interestingly, in adipose tissue Cidea protein expression was significantly related to body weight (R=.725), epididymal adipose tissue (EWAT) mass (R=.475) and insulin resistance (R=.706), whereas Cidec protein expression was inversely related to body weight (R=-.787), EWAT mass (R=-.706), and insulin resistance (R=-.679). Similar to adipose tissue, Cidea protein expression in liver was significantly related to body weight (R=.660), EWAT mass (R=.468), and insulin resistance (R=.599); however, unlike adipose tissue, Cidec protein levels in liver were not related to body weight or EWAT mass and only moderately associated with insulin resistance (R=-.422, P=0.051). Overall, our findings indicate that Cidea is highly associated with adiposity and insulin resistance, whereas Cidec is related to insulin sensitivity. The present study suggests that Cide proteins might play an important functional role in the development of obesity, hepatic steatosis, as well as the pathogenesis of type 2 diabetes.

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Section: Resultsmentioning

confidence: 99%

Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice

et al. 2015

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“…Excitingly, we found the interplay between Abra (STARS) and its targets, Srf and Egr1. These three TFs have an important role in the remodeling, homeostasis and metabolism of skeletal muscle [ 95 ], and appear to be under control of AKT [ 96 ]. In the SiHa Gal-7+ TAM, there is not an obvious interplay between the predicted and regulated TFs.…”

Section: Discussionmentioning

confidence: 99%

Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment

et al. 2016

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BackgroundGalectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited.MethodsMeta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn’s Multiple Comparison and T tests. Kaplan–Meier and log-rank tests were used to determine overall survival.ResultsGal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples.ConclusionsGal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2700-8) contains supplementary material, which is available to authorized users.

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“…Moreover, direct (Senf et al, 2010) and indirect (Senf et al, 2008) inhibition of FOXO transcription activity has been shown to attenuate disuse-induced muscle loss. The exact mechanism by which the FOXO transcription factors are activated is unclear since the FOXO transcription factors are not always activated by a decrease in Akt/PKB activity (Reynolds et al, 2012), and Akt/PKB activity is not always decreased in response to unloading (Marimuthu et al, 2011). …”

Section: Attenuation Of Disuse-induced Atrophymentioning

confidence: 99%

Disuse-induced muscle wasting

Bodine¹

2013

The International Journal of Biochemistry & Cell Biology

305

256

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Loss of skeletal muscle mass occurs frequently in clinical settings in response to joint immobilization and bed rest, and is induced by a combination of unloading and inactivity. Disuse-induced atrophy will likely affect every person in his or her lifetime, and can be debilitating especially in the elderly. Currently there are no good therapies to treat disuse-induced muscle atrophy, in part, due to a lack of understanding of the cellular and molecular mechanisms responsible for the induction and maintenance of muscle atrophy. Our current understanding of disuse atrophy comes from the investigation of a variety of models (joint immobilization, hindlimb unloading, bed rest, spinal cord injury) in both animals and humans. Under conditions of unloading, it is widely accepted that there is a decrease in protein synthesis, however, the role of protein degradation, especially in humans, is debated. This review will examine the current understanding of the molecular and cellular mechanisms regulating muscle loss under disuse conditions, discussing the similarities and areas of dispute between the animal and human literature.

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Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice

Abstract: Reynolds 4th TH, Merrell E, Cinquino N, Gaugler M, Ng L. Disassociation of insulin action and Akt/FOXO signaling in skeletal muscle of older Akt-deficient mice.

Cited by 11 publications

References 32 publications

Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice

Effects of a High Fat Diet and Voluntary Wheel Running Exercise on Cidea and Cidec Expression in Liver and Adipose Tissue of Mice

Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment

Disuse-induced muscle wasting

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