TCF7L2 plays a complex role in human adipose progenitor biology, which might contribute to genetic susceptibility to type 2 diabetes

Verma, Manu; Loh, Nellie Y.; Sabaratnam, Rugivan; Vasan, Senthil K.; Dam, Anke; Todorčević, Marijana; Neville, Matthew J.; Toledo, Enrique M.; Karpe, Fredrik; Christodoulides, Constantinos

doi:10.1016/j.metabol.2022.155240

Cited by 10 publications

(13 citation statements)

References 72 publications

(102 reference statements)

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“…The GWAS study of human T2DM has accumulated hundreds of related gene loci, such as TCF7L2, PPARG, and KCNJ11. [14][15][16] In addition, various SNP analyses have been used in the genetic research of T2DM. [17][18][19] However, obvious ethnic and regional differences exist in the combinations of susceptibility genes due to the genetic heterogeneity of T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…It has good repeatability in different ethnic groups, and the genotype of rs7903146 is considered to be associated with the risk of human T2DM. 15,22 Functionally, the risk allele of SNP rs7903146 has been associated with a reduced incretin effect and reduced insulin release during the oral glucose tolerance test. 23,24 The polymorphisms of HHEX rs1111875 and rs5015480 are also considered to be associated with insulin secretion and beta-cell dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, using SNP as a genetic marker to screen for T2DM susceptibility genes is a very effective high‐efficiency, low‐cost method. The GWAS study of human T2DM has accumulated hundreds of related gene loci, such as TCF7L2, PPARG, and KCNJ11 14–16 . In addition, various SNP analyses have been used in the genetic research of T2DM 17–19 …”

Section: Discussionmentioning

confidence: 99%

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Whole‐genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs

Niu

Zhao

Jia

et al. 2023

Anim Models and Exp Med

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BackgroundHundreds of single‐nucleotide polymorphism (SNP) sites have been found to be potential genetic markers of type 2 diabetes mellitus (T2DM). However, SNPs related to T2DM in minipigs have been less reported. This study aimed to screen the T2DM‐susceptible candidate SNP loci in Bama minipigs so as to improve the success rate of the minipig T2DM model.MethodsThe genomic DNAs of three Bama minipigs with T2DM, six sibling low‐susceptibility minipigs with T2DM, and three normal control minipigs were compared by whole‐genome sequencing. The T2DM Bama minipig‐specific loci were obtained, and their functions were annotated. Meanwhile, the Biomart software was used to perform homology alignment with T2DM‐related loci obtained from the human genome‐wide association study to screen candidate SNP markers for T2DM in Bama miniature pigs.ResultsWhole‐genome resequencing detected 6960 specific loci in the minipigs with T2DM, and 13 loci corresponding to 9 diabetes‐related genes were selected. Further, a set of 122 specific loci in 69 orthologous genes of human T2DM candidate genes were obtained in the pigs. Collectively, a batch of T2DM‐susceptible candidate SNP markers in Bama minipigs, covering 16 genes and 135 loci, was established.ConclusionsWhole‐genome sequencing and comparative genomics analysis of the orthologous genes in pigs that corresponded to the human T2DM‐related variant loci successfully screened out T2DM‐susceptible candidate markers in Bama miniature pigs. Using these loci to predict the susceptibility of the pigs before constructing an animal model of T2DM may help to establish an ideal animal model.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Whole‐genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs

Niu

Zhao

Jia

et al. 2023

Anim Models and Exp Med

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“…Besides, the altered splicing pattern of transcription factor 7 like 2 (TCF7L2) was validated in ASO-SNORD116 adipocytes. The TCF7L2 gene encodes a transcription factor that plays a key role in the Wnt/β-catenin signaling pathway and has been implicated in AT biology, glucose homeostasis, and lipid metabolism [52]. Genome-wide association studies suggest a strong association between TCF7L2 genetic variants and an increased risk of type 2 diabetes in humans [53].…”

Section: Discussionmentioning

confidence: 99%

Dysregulated adipose tissue expansion and impaired adipogenesis in Prader-Willi syndrome children before obesity-onset

Chao¹,

Gao²,

Wang³

et al. 2022

Metabolism

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“…The intronic variant rs7903146 (T allele) of TCF7L2 is the SNP that is the strongest genetic determinant of T2D known so far, leading to an increased risk of T2D by 41% [ 40 ]. Genetic variants of TCF7L2 influence pancreatic insulin secretion, and might influence T2D risk by modulating adipogenesis [ 41 ].…”

Section: Risk Factors For T2d In Young Individuals With Metsmentioning

confidence: 99%

From Metabolic Syndrome to Type 2 Diabetes in Youth

et al. 2023

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In the frame of metabolic syndrome, type 2 diabetes emerges along a continuum of the risk from the clustering of all its components, namely visceral obesity, high blood pressure and lipids, and impaired glucose homeostasis. Insulin resistance is the hallmark common to all the components and, in theory, is a reversible condition. Nevertheless, the load that this condition can exert on the β-cell function at the pubertal transition is such as to determine its rapid and irreversible deterioration leading to plain diabetes. The aim of this review is to highlight, in the context of metabolic syndrome, age-specific risk factors that lead to type 2 diabetes onset in youth; resume age specific screening and diagnostic criteria; and anticipate potential for treatment. Visceral obesity and altered lipid metabolism are robust grounds for the development of the disease. Genetic differences in susceptibility to hampered β-cell function in the setting of obesity and insulin resistance largely explain why some adolescents with obesity do develop diabetes at a young age and some others do not. Lifestyle intervention with a healthy diet and physical activity remains the pillar of the type 2 diabetes treatment in youth. As to the pharmacological management, metformin and insulin have failed to rescue β-cell function and to ensure long-lasting glycemic control in youth. A new era might start with the approval for use in pediatric age of drugs largely prescribed in adults, such as dipeptidyl peptidase-4 and sodium-dependent glucose transport inhibitors, and of new weight-lowering drugs in the pipeline such as single and multiple agonists of the glucagon-like peptide 1 receptor. The latter drugs can have tremendous impact on the natural history of the disease. By treating diabetes, they will reduce the burden of all the metabolic abnormalities belonging to the syndrome while causing a tremendous weight loss hitherto never seen before.

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TCF7L2 plays a complex role in human adipose progenitor biology, which might contribute to genetic susceptibility to type 2 diabetes

Cited by 10 publications

References 72 publications

Whole‐genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs

Whole‐genome sequencing study to identify candidate markers indicating susceptibility to type 2 diabetes in Bama miniature pigs

Dysregulated adipose tissue expansion and impaired adipogenesis in Prader-Willi syndrome children before obesity-onset

From Metabolic Syndrome to Type 2 Diabetes in Youth

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