The role of transcription factor 7‐like 2 in metabolic disorders

Zhang, Zhensheng; Xu, Li; Xu, Xiao Yan

doi:10.1111/obr.13166

Cited by 14 publications

(8 citation statements)

References 192 publications

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“…The TCF7L2 rs7903146 SNP is the most important genetic predictor of T2DM [ 20 ]. Disturbances in insulin sensitivity and induction of insulin resistance are among the molecular mechanisms through which TCF7L2 rs7903146 variant increases the risk of T2DM [ 43 ]. Although the role of insulin resistance in inducing inflammation has been identified [ 25 ], the effect of TCF7L2 gene on inflammation has been less investigated [ 26 , 27 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of TCF7L2 polymorphisms on inflammatory markers after 16 weeks of legume-based dietary approach to stop hypertension (DASH) diet versus a standard DASH diet: a randomised controlled trial

et al. 2022

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Backgrounds This randomized controlled trial aimed to investigate the effects of replacing red meat with legumes in the dietary approach to stop hypertension (DASH) diet on inflammatory markers over 16 weeks in overweight and obese individuals with type 2 diabetes. Also, the modulatory effects of TCF7L2 rs7903146 variant on this effect were assessed. Methods In this trial, 300 participants with type 2 diabetes, aged 30–65 years with an identified TCF7L2 rs7903146 genotype, were studied. The participants were randomly assigned to the DASH diet or the legume-based DASH diet over 16 weeks. In the DASH diet group, the participants were instructed to follow the standard DASH diet. The legume-based DASH diet was similar to the standard DASH diet, with the exception that one serving of red meat was replaced with one serving of legumes at least five days a week. At the beginning of the study and 16-week follow-up, venous blood samples were collected from all participants who fasted for 12–14 h overnight. The serum concentration of High-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the serum malondialdehyde (MDA) concentration was assessed based on a colorimetric method using a commercial kit. The primary outcome was the difference in hs-CRP changes between the diets. A secondary outcomes was the difference in IL-6, TNF-α, and MDA between the groups among total population and based on TCF7L2 rs7903146 risk allele (CT + TT) and non-risk allele (CC) separately. Results The hs-CRP level reduced in the legume-based DASH diet group as compared to the DASH diet group in the 16-week follow-up group. The levels of TNF-α, IL-6, and MDA reduced after the legume-based DASH diet relative to the DASH diet. Reduction of inflammatory markers was observed in both carriers of rs7903146 risk allele and non-risk allele. Conclusions Substituting one serving of red meat with one serving of legumes in DASH diet, at least five days a week, could improve the hs-CRP, TNF-α, IL-6, and MDA in participants with type 2 diabetes regardless of having rs7903146 risk or non-risk allele. Trial registration IRCT, IRCT20090203001640N17.

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Section: Discussionmentioning

confidence: 99%

The effect of TCF7L2 polymorphisms on inflammatory markers after 16 weeks of legume-based dietary approach to stop hypertension (DASH) diet versus a standard DASH diet: a randomised controlled trial

et al. 2022

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“…It has been shown recently, however, that the reduction of the transcription factor 7-like 2 (TCF7L2) expression level, which is a transcription factor and plays a crucial role in the maintenance of β-cell function, is involved in the downregulation of incretin receptor expression in β-cells [ 31 , 32 , 33 ]. It has been reported that TCF7L2 is involved in insulin biosynthesis, secretion and preservation of β-cell mass through the AKT and mTOR pathway [ 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. Indeed, it is known that inactivation of TCF7L2 leads to the impairment of insulin secretion and glucose tolerance.…”

Section: Incretin and Pancreatic β-Cellsmentioning

confidence: 99%

Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

Kaneto

Kimura

Shimoda

et al. 2021

IJMS

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Fundamental pancreatic β-cell function is to produce and secrete insulin in response to blood glucose levels. However, when β-cells are chronically exposed to hyperglycemia in type 2 diabetes mellitus (T2DM), insulin biosynthesis and secretion are decreased together with reduced expression of insulin transcription factors. Glucagon-like peptide-1 (GLP-1) plays a crucial role in pancreatic β-cells; GLP-1 binds to the GLP-1 receptor (GLP-1R) in the β-cell membrane and thereby enhances insulin secretion, suppresses apoptotic cell death and increase proliferation of β-cells. However, GLP-1R expression in β-cells is reduced under diabetic conditions and thus the GLP-1R activator (GLP-1RA) shows more favorable effects on β-cells at an early stage of T2DM compared to an advanced stage. On the other hand, it has been drawing much attention to the idea that GLP-1 signaling is important in arterial cells; GLP-1 increases nitric oxide, which leads to facilitation of vascular relaxation and suppression of arteriosclerosis. However, GLP-1R expression in arterial cells is also reduced under diabetic conditions and thus GLP-1RA shows more protective effects on arteriosclerosis at an early stage of T2DM. Furthermore, it has been reported recently that administration of GLP-1RA leads to the reduction of cardiovascular events in various large-scale clinical trials. Therefore, we think that it would be better to start GLP-1RA at an early stage of T2DM for the prevention of arteriosclerosis and protection of β-cells against glucose toxicity in routine medical care.

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“…Transcription factor 7-like 2 (TCF7L2) is a member of the T-cell factor/lymphoid enhancer factor family and serves as a crucial transcription factor within the canonical Wnt signaling pathway. It constructs a compound with β-catenin and acts as a key regulator of downstream target genes, thereby facilitating tumor progression [ 22 ]. TCF7L2 is involved in cellular metabolic reprogramming, and studies have shown that TCF7L2 down-regulates hepatic gluconeogenesis while promoting lipid accumulation [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

HIF2α Promotes Cancer Metastasis through TCF7L2-Dependent Fatty Acid Synthesis in ccRCC

Shi,

Lv,

Miao

et al. 2024

Research

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Recent studies have highlighted the notable involvement of the crosstalk between hypoxia-inducible factor 2 alpha (HIF2α) and Wnt signaling components in tumorigenesis. However, the cellular function and precise regulatory mechanisms of HIF2α and Wnt signaling interactions in clear cell renal cell carcinoma (ccRCC) remain elusive. To analyze the correlation between HIF2α and Wnt signaling, we utilized the Cancer Genome Atlas - Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) public database, HIF2α RNA sequencing data, and conducted luciferase reporter assays. A Wnt-related gene set was employed to identify key regulators of Wnt signaling controlled by HIF2α in ccRCC. Furthermore, we assessed the biological effects of TCF7L2 on ccRCC metastasis and lipid metabolism in both in vivo and in vitro settings. Our outcomes confirm TCF7L2 as a key gene involved in HIF2α-mediated regulation of the canonical Wnt pathway. Functional studies demonstrate that TCF7L2 promotes metastasis in ccRCC. Mechanistic investigations reveal that HIF2α stabilizes TCF7L2 mRNA in a method based on m 6 A by transcriptionally regulating METTL3. Up-regulation of TCF7L2 enhances cellular fatty acid oxidation, which promotes histone acetylation. This facilitates the transcription of genes connected to epithelial–mesenchymal transition and ultimately enhances metastasis of ccRCC. These outcomes offer a novel understanding into the involvement of lipid metabolism in the signaling pathway regulation, offering valuable implications for targeted treatment in ccRCC.

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The role of transcription factor 7‐like 2 in metabolic disorders

Cited by 14 publications

References 192 publications

The effect of TCF7L2 polymorphisms on inflammatory markers after 16 weeks of legume-based dietary approach to stop hypertension (DASH) diet versus a standard DASH diet: a randomised controlled trial

The effect of TCF7L2 polymorphisms on inflammatory markers after 16 weeks of legume-based dietary approach to stop hypertension (DASH) diet versus a standard DASH diet: a randomised controlled trial

Favorable Effects of GLP-1 Receptor Agonist against Pancreatic β-Cell Glucose Toxicity and the Development of Arteriosclerosis: “The Earlier, the Better” in Therapy with Incretin-Based Medicine

HIF2α Promotes Cancer Metastasis through TCF7L2-Dependent Fatty Acid Synthesis in ccRCC

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