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Original Article
Basic Research
Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men
Laura G.M. Janssen, Andrea D. van Dam, Mark J.W. Hanssen, Sander Kooijman, Kimberly J. Nahon, Hanneke Reinders, Ingrid M. Jazet, Wouter D. van Marken Lichtenbelt, Patrick C.N. Rensen, Natasha M. Appelman-Dijkstra, Mariëtte R. Boon
Diabetes Metab J. 2020;44(2):326-335.   Published online October 31, 2019
DOI: https://doi.org/10.4093/dmj.2019.0031
  • 6,054 View
  • 80 Download
  • 11 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
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.

Citations

Citations to this article as recorded by  
  • Insights on effects of Wnt pathway modulation on insulin signaling and glucose homeostasis for the treatment of type 2 diabetes mellitus: Wnt activation or Wnt inhibition?
    Ruchi Yadav, Bhumika Patel
    International Journal of Biological Macromolecules.2024; : 129634.     CrossRef
  • Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait
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    Frontiers in Bioengineering and Biotechnology.2022;[Epub]     CrossRef
  • Subcutaneous adipose tissue sclerostin is reduced and Wnt signaling is enhanced following 4‐weeks of sprint interval training in young men with obesity
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    Physiological Reports.2022;[Epub]     CrossRef
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    Federico Carbone, Elisa Nulli Migliola, Aldo Bonaventura, Alessandra Vecchié, Stefano De Vuono, Maria Anastasia Ricci, Gaetano Vaudo, Marcello Boni, Stefano Ministrini, Graziana Lupattelli, Fabrizio Montecucco
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    Jaak Jürimäe, Vita Karvelyte, Liina Remmel, Anna-Liisa Tamm, Priit Purge, Rita Gruodyte-Raciene, Sigitas Kamandulis, Katre Maasalu, Luis Gracia-Marco, Vallo Tillmann
    Journal of Pediatric Endocrinology and Metabolism.2021; 34(6): 755.     CrossRef
  • The complex role of Wnt ligands in type 2 diabetes mellitus and related complications
    Xiaobo Nie, Xiaoyun Wei, Han Ma, Lili Fan, Wei‐Dong Chen
    Journal of Cellular and Molecular Medicine.2021; 25(14): 6479.     CrossRef
Review
Pathophysiology
Primary Cilia as a Signaling Platform for Control of Energy Metabolism
Do Kyeong Song, Jong Han Choi, Min-Seon Kim
Diabetes Metab J. 2018;42(2):117-127.   Published online April 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.42.2.117
  • 8,866 View
  • 144 Download
  • 28 Web of Science
  • 26 Crossref
AbstractAbstract PDFPubReader   

Obesity has become a common healthcare problem worldwide. Cilia are tiny hair-like organelles on the cell surface that are generated and anchored by the basal body. Non-motile primary cilia have been considered to be evolutionary rudiments until a few decades, but they are now considered as important signaling organelles because many receptors, channels, and signaling molecules are highly expressed in primary cilia. A potential role of primary cilia in metabolic regulation and body weight maintenance has been suspected based on rare genetic disorders termed as ciliopathy, such as Bardet-Biedl syndrome and Alström syndrome, which manifest as obesity. Recent studies have demonstrated involvement of cilia-related cellular signaling pathways in transducing metabolic information in hypothalamic neurons and in determining cellular fate during adipose tissue development. In this review, we summarize the current knowledge about cilia and cilia-associated signaling pathways in the regulation of body metabolism.

Citations

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