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Increasing brown adipose tissue (BAT) activity is regarded as a potential treatment of obese, hyperglycemic patients with metabolic syndrome. Triiodothyronine (T3) is known to stimulate BAT activity by increasing mitochondrial uncoupling protein 1 (Ucp1) gene transcription, leading to increased thermogenesis and decreased body weight. Here we report our studies on the effects of T3 and glucose in two mouse models and in mouse immortalized brown preadipocytes in culture. We identified carbohydrate response element binding protein (ChREBP) as a T3 target gene in BAT by RNA sequencing and studied its effects in brown adipocytes. We found that ChREBP was upregulated by T3 in BAT in both hyperglycemic mouse models. In brown preadipocytes, T3 and glucose synergistically and dose dependently upregulated Ucp1 messenger RNA 1000-fold compared with low glucose concentrations. Additionally, we observed increased ChREBP and Ucp1 protein 11.7- and 19.9-fold, respectively, along with concomitant induction of a hypermetabolic state. Moreover, downregulation of ChREBP inhibited T3 and glucose upregulation of Ucp1 100-fold, whereas overexpression of ChREBP upregulated Ucp1 5.2-fold. We conclude that T3 and glucose signaling pathways coordinately regulate the metabolic state of BAT and suggest that ChREBP is a target for therapeutic regulation of BAT activity.
Pubmed ID: 29077876 RIS Download
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A tool for performing multi-cluster gene functional enrichment analyses on large scale data (microarray experiments with many time-points, cell-types, tissue-types, etc.). It facilitates co-analysis of multiple gene lists and yields as output a rich functional map showing the shared and list-specific functional features. The output can be visualized in tabular, heatmap or network formats using built-in options as well as third-party software. It uses the hypergeometric test to obtain functional enrichment achieved via the gene list enrichment analysis option available in ToppGene.
View all literature mentionsCommercial antibody vendor which supplies antibodies and other products to life science researchers.
View all literature mentionsA clustering software package for identification of enriched domains from histone modification ChIP-Seq data.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets Thyroid Hormone Receptor antibody [C3]
View all literature mentionsThis monoclonal targets GAPDH antibody [6C5]
View all literature mentionsThis polyclonal targets CHREBP
View all literature mentionsThis monoclonal targets UCP1 antibody produced in mouse
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