About: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice

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About: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice
Creator	Da, Gabriela Leclerc, Isabelle Martinez-Sanchez, Aida Nguyen-Tu, Marie-Sophie Rutter, Guy Xavier, Silva
Source	BioRxiv
abstract	Transcription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/beta-catenin signalling pathway and its expression is critical for adipocyte development. The precise role of TCF7L2 in glucose and lipid metabolism in adult adipocytes remains to be defined. Here, we aim to investigate how changes in TCF7L2 expression in mature adipocytes affect glucose homeostasis. Tcf7l2 was selectively ablated from mature adipocytes in C57BL/6J mice using an adiponectin promoter-driven Cre recombinase to recombine alleles floxed at exon 1 of the Tcf7l2 gene. Mice lacking Tcf7l2 in mature adipocytes displayed normal body weight. Male mice exhibited normal glucose homeostasis at eight weeks of age. Male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance (AUC increased 1.14 ± 0.04 -fold, p=0.03), as assessed by intraperitoneal glucose tolerance test, and changes in fat mass at 16 weeks (increased by 1.4 ± 0.09-fold, p=0.007). Homozygote knockout mice exhibited impaired oral glucose tolerance at 16 weeks of age (AUC increased 2.15 ± 0.15-fold, p=0.0001). Islets of Langerhans exhibited impaired glucose-stimulated insulin secretion in vitro (decreased 0.54 ± 0.13-fold aTCF7L2KO vs control, p=0.02), but no changes in in vivo glucose-stimulated insulin secretion. Female mice in which one or two alleles of the Tcf7l2 gene was knocked out in adipocytes displayed no changes in glucose tolerance, insulin sensitivity or insulin secretion. Plasma levels of glucagon-like peptide-1 and gastric inhibitory polypeptide were lowered in knockout mice (decreased 0.57 ± 0.03-fold and 0.41 ± 0.12-fold, p=0.04 and p=0.002, respectively), whilst plasma free fatty acids and Fatty Acid Binding Protein 4 circulating levels were increased by 1.27 ± 0.07 and 1.78 ± 0.32-fold, respectively (p=0.05 and p=0.03). Mice with biallelic Tcf7l2 deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reduced in vivo glucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Thus, our data indicate that loss of Tcf7l2 gene expression in adipocytes leads to impairments on metabolic responses which are dependent on gender, age and nutritional status. Our findings further illuminate the role of TCF7L2 in the maintenance of glucose homeostasis.
has issue date	2020-05-20(xsd:dateTime)
bibo:doi	10.1101/2020.05.18.102384
has license	biorxiv
sha1sum (hex)	f8173d89781dddb24808cb36f622e968f2f83913
schema:url	https://doi.org/10.1101/2020.05.18.102384
resource representing a document's title	Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice
schema:publication	bioRxiv
resource representing a document's body	covid:f8173d89781dddb24808cb36f622e968f2f83913#body_text
is schema:about of	named entity 'normal' named entity 'age' named entity 'glucose tolerance test' named entity 'secretion' named entity 'weeks' named entity 'Tcf7l2' named entity 'oral' named entity 'effector' named entity 'adipocytes' named entity 'C57BL/6J' named entity 'selectively' named entity 'adipocyte' named entity 'development' named entity 'affect' named entity 'fold' named entity 'Wnt' named entity 'adipocytes' named entity 'AUC' named entity 'fat' named entity 'adiponectin' named entity 'TCF7L2' named entity 'remains' named entity 'Tcf7l2' named entity 'knockout mice' named entity 'Male' named entity 'TCF7L2' named entity 'glucose tolerance' named entity 'insulin' named entity 'Wnt/beta-catenin' named entity 'normal body weight' named entity 'insulin secretion' named entity 'ablated' named entity '1.14' named entity 'TCF7L2' named entity 'adipocytes' named entity 'Tcf7l2' named entity 'C57BL/6J' named entity 'downstream effector' named entity 'adipocytes' named entity 'Tcf7l2' named entity 'Mice' named entity 'Tcf7l2' named entity 'Transcription factor' named entity 'adipocyte' named entity 'insulin secretion' named entity 'lipid metabolism' named entity 'Langerhans' named entity 'mice' named entity 'beta cell' named entity 'Tcf7l2' named entity 'incretin' named entity 'LEF-1' named entity 'biallelic' named entity 'binding domain' named entity 'glucose' named entity 'Wnt signalling' named entity 'phosphorylation' named entity 'Tcf7l2' named entity 'mice' named entity 'adipocyte' named entity 'ng/mL' named entity 'plasma' named entity 'Germany' named entity 'hepatic' named entity 'triglycerides' named entity 'cell type' named entity 'chaperone' named entity 'Germany' named entity 'Cre recombinase' named entity 'rs7903146' named entity 'TCF7L2' named entity 'female hormones' named entity 'liquid nitrogen' named entity 'lipolysis' named entity 'TCF7L2' named entity 'ng/mL' named entity 'mmol/l' named entity 'digestion' named entity 'causal relationship'

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