Wnt Signaling Genes in Adipose Tissue and Skeletal Muscle of Humans With Different Degrees of Insulin Sensitivity

Karczewska-Kupczewska, Monika; Stefanowicz, Magdalena; Matulewicz, Natalia; Nikołajuk, Agnieszka; Strączkowski, Marek

doi:10.1210/jc.2016-1594

Cited by 52 publications

(49 citation statements)

References 34 publications

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“…Whether these alterations in the Wnt pathway are congenital or possibly induced by increased sclerostin levels later in life, remains to be explored. Interestingly, Karczewska-Kupczewska et al [33] also previously showed in an euglycemic clamp study that expression of various Wnt signaling genes in WAT was lower in nondiabetic individuals with low versus high insulin sensitivity. Indeed, in our study expression of key insulin genes (INSR, TBC1D4, SLC2A4, and GYS1) in WAT was also lower in South Asians compared with white Caucasians, suggesting that Wnt and insulin signaling in WAT are associated and that lower Wnt signaling might partially reduce insulin signaling in South Asians.…”

Section: Discussionmentioning

confidence: 91%

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

et al. 2020

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Background: South Asians generally have an unfavourable metabolic phenotype compared with white Caucasians, including central obesity and insulin resistance. The Wnt protein family interacts with insulin signaling, and impaired Wnt signaling is associated with adiposity and type 2 diabetes mellitus. We aimed to investigate Wnt signaling in relation to insulin signaling in South Asians compared with white Caucasians. Methods: Ten Dutch South Asian men with prediabetes and overweight or obesity and 10 matched Dutch white Caucasians were included. Blood samples were assayed for the Wnt inhibitor sclerostin. Subcutaneous white adipose tissue (WAT) and skeletal muscle biopsies were assayed for Wnt and insulin signaling gene expression with quantitative reverse transcription polymerase chain reaction (Clinicaltrials.gov NCT02291458). Results: Plasma sclerostin was markedly higher in South Asians compared with white Caucasians (+65%, P<0.01). Additionally, expression of multiple Wnt signaling genes and key insulin signaling genes were lower in WAT in South Asians compared with white Caucasians. Moreover, in WAT in both ethnicities, Wnt signaling gene expression strongly positively correlated with insulin signaling gene expression. In skeletal muscle, WNT10B expression in South Asians was lower, but expression of other Wnt signaling and insulin signaling genes was comparable between ethnicities. Wnt and insulin signaling gene expression also positively correlated in skeletal muscle, albeit less pronounced. Conclusion: South Asian men with overweight or obesity and prediabetes have higher plasma sclerostin and lower Wnt signaling gene expression in WAT compared with white Caucasians. We interpret that reduced Wnt signaling could contribute to impaired insulin signaling in South Asians.

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Section: Discussionmentioning

confidence: 91%

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

et al. 2020

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“…Sclerostin influences SCI-induced bone loss, as evidenced by (1) increased sclerostin mRNA expression in bone acutely after SCI [ 7 ], (2) mice with sclerostin gene deletion that do not exhibit bone loss after spinal cord transection [ 9 ], and (3) the ability pharmacologic sclerostin-inhibition to completely prevent cancellous bone loss in rats following SCI [ 2 , 10 ]. Others have suggested that sclerostin may also influence skeletal muscle [ 5 ], a supposition that is strengthened by the understanding that sclerostin is present in the circulation [ 8 ], that LRP5/LRP6 are expressed in human muscle [ 11 , 12 ], and that the Wnt/β-catenin signaling pathway is anabolic in muscle [ 3 ]. Interestingly, Huang et al recently reported that Wnt3a, an osteocyte-derived Wnt-signaling agonist, promoted C2C12 cell differentiation in vitro and that sclerostin co-incubation (100 ng/ml) prevented this effect [ 13 ], demonstrating that sclerostin negatively regulates Wnt-signaling in a mouse skeletal muscle cell line, at least when present in relatively high concentrations.…”

Section: Introductionmentioning

confidence: 99%

Effects of pharmacologic sclerostin inhibition or testosterone administration on soleus muscle atrophy in rodents after spinal cord injury

Phillips

Beggs

et al. 2018

PLoS ONE

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Sclerostin is a circulating osteocyte-derived glycoprotein that negatively regulates Wnt-signaling after binding the LRP5/LRP6 co-receptors. Pharmacologic sclerostin inhibition produces bone anabolic effects after spinal cord injury (SCI), however, the effects of sclerostin-antibody (Scl-Ab) on muscle morphology remain unknown. In comparison, androgen administration produces bone antiresorptive effects after SCI and some, but not all, studies have reported that testosterone treatment ameliorates skeletal muscle atrophy in this context. Our purposes were to determine whether Scl-Ab prevents hindlimb muscle loss after SCI and compare the effects of Scl-Ab to testosterone enanthate (TE), an agent with known myotrophic effects. Male Sprague-Dawley rats aged 5 months received: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe contusion SCI, (C) SCI+TE (7.0 mg/wk, im), or (D) SCI+Scl-Ab (25 mg/kg, twice weekly, sc). Twenty-one days post-injury, SCI animals exhibited a 31% lower soleus mass in comparison to SHAM, accompanied by >50% lower soleus muscle fiber cross-sectional area (fCSA) (p<0.01 for all fiber types). Scl-Ab did not prevent soleus atrophy, consistent with the relatively low circulating sclerostin concentrations and with the 91–99% lower LRP5/LRP6 gene expressions in soleus versus tibia (p<0.001), a tissue with known anabolic responsiveness to Scl-Ab. In comparison, TE partially prevented soleus atrophy and increased levator ani/bulbocavernosus (LABC) mass by 30–40% (p<0.001 vs all groups). The differing myotrophic responsiveness coincided with a 3-fold higher androgen receptor gene expression in LABC versus soleus (p<0.01). This study provides the first direct evidence that Scl-Ab does not prevent soleus muscle atrophy in rodents after SCI and suggests that variable myotrophic responses in rodent muscles after androgen administration are influenced by androgen receptor expression.

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“…MyoD1 is able to promote the transformation of multipotent stem cells to skeletal muscle by binding and activating the expression of a subset of pre-myogenic mesoderm genes, including Six1 [52]. And gene Ctnnb1 modulates skeletal muscle development by acting on transcription factors controlling myogenesis such as MyoD [53].…”

Section: Rna-seq Data Validationmentioning

confidence: 99%

Integrative methylome and transcriptome analysis of Japanese flounder (Paralichthys olivaceus) skeletal muscle during development

Zhang

et al. 2019

Preprint

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DNA methylation is an important epigenetic modification in vertebrate andis essential for epigenetic gene regulation in skeletal muscle development. We showed the genome-wide DNA methylation profile in skeletal muscle tissue of larval 7dph (JP1), juvenile 90dph (JP2), adult female 24 months (JP3) and adult male 24 months (JP4) Japanese flounder. The distribution and levels of methylated DNA within genomic features (1stexons, gene body, introns, TSS200, TSS1500 and intergenic) show different developmental landscapes. We also 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 1 2 successfully identified differentially methylated regions (DMRs) and different methylated genes (DMGs) through a comparative analysis, indicating that DMR in gene body, intron and intergenic regions were more compared to other regions of all DNA elements. A gene ontology analysis indicated that the DMGs were mainly related to regulation of skeletal muscle fiber development process, Axon guidance, Adherens junction, and some ATPase activity. Methylome and transcriptome clearly revealed a exhibit a negative correlation. And integration analysis revealed a total of 425, 398 and 429 negatively correlated genes with methylation in the JP2_VS_JP1, JP3_VS_JP1 and JP4_VS_JP1 comparison groups, respectively. And these genes were functionally associated with pathways including Adherens junction, Axon guidance, Focal adhesion, cell junctions, Actin cytoskeleton and Wnt signaling pathways. In addition, we validated the MethylRAD results by bisulfite sequencing PCR (BSP) in some of the differentially methylated skeletal muscle growth-related genes (Myod1, Six1 and Ctnnb1). In this study, we have generated the genome-wide profile of methylome and transcriptome in Japanese flounder for the first time, and our results bring new insights into the epigenetic regulation of developmental processes in Japanese flounder. This study contributes to the knowledge on epigenetics in vertebrates. Author summaryEpigenetic mechanisms like DNA methylation have recently reported as vital regulators of some species skeletal muscle development through the control of genes related to growth. To date, although genome-wide DNA methylation profiles of many organisms have been reported and the Japanese flounder reference genome and whole transcriptome data are publically available, the methylation pattern of Japanese flounder skeletal muscle tissue remains minimally studied and the global DNA methylation data are yet to be known. Here we investigated the genome-wide DNA methylation patterns in Japanese flounder, throughout its development. These findings help to enrich research in molecular and developmental biology in vertebrates.

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Wnt Signaling Genes in Adipose Tissue and Skeletal Muscle of Humans With Different Degrees of Insulin Sensitivity

Abstract: The association of β-catenin-dependent Wnt signaling with insulin resistance is tissue specific. Observed changes might reflect a compensatory mechanism to increase muscle glucose uptake and to generate new fat cells in insulin-resistant conditions.

Cited by 52 publications

References 34 publications

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

Effects of pharmacologic sclerostin inhibition or testosterone administration on soleus muscle atrophy in rodents after spinal cord injury

Integrative methylome and transcriptome analysis of Japanese flounder (Paralichthys olivaceus) skeletal muscle during development

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