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      The Molecular Characteristics of the FAM13A Gene and the Role of Transcription Factors ACSL1 and ASCL2 in Its Core Promoter Region

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          Abstract

          The gene family with sequence similarity 13 member A ( FAM13A) has recently been identified as a marker gene in insulin sensitivity and lipolysis. In this study, we first analyzed the expression patterns of this gene in different tissues of adult cattle and then constructed a phylogenetic tree based on the FAM13A amino acid sequence. This showed that subcutaneous adipose tissue had the highest expression in all tissues except lung tissue. Then we summarized the gene structure. The promoter region sequence of the gene was successfully amplified, and the −241/+54 region has been identified as the core promoter region. The core promoter region was determined by the unidirectional deletion of the 5’ flanking promoter region of the FAM13A gene. Based on the bioinformatics analysis, we examined the dual luciferase activity of the vector constructed by the mutation site, and the transcription factors ACSL1 and ASCL2 were found as transcriptional regulators of FAM13A. Moreover, electrophoretic mobility shift assay (EMSA) further validated the regulatory role of ACSL1 and ASCL2 in the regulation of FAM13A. ACSL1 and ASCL2 were finally identified as activating transcription factors. Our results provide a basis for the function of the FAM13A gene in bovine adipocytes in order to improve the deposition of fat deposition in beef cattle muscle.

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          Regulation of lipolysis in adipocytes.

          Lipolysis of white adipose tissue triacylglycerol stores results in the liberation of glycerol and nonesterified fatty acids that are released into the vasculature for use by other organs as energy substrates. In response to changes in nutritional state, lipolysis rates are precisely regulated through hormonal and biochemical signals. These signals modulate the activity of lipolytic enzymes and accessory proteins, allowing for maximal responsiveness of adipose tissue to changes in energy requirements and availability. Recently, a number of novel adipocyte triacylglyceride lipases have been identified, including desnutrin/ATGL, greatly expanding our understanding of adipocyte lipolysis. We have also begun to better appreciate the role of a number of nonenzymatic proteins that are critical to triacylglyceride breakdown. This review provides an overview of key mediators of lipolysis and the regulation of this process by changes in nutritional status and nutrient intakes.
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            The Sjögren-Larsson syndrome gene encodes a hexadecenal dehydrogenase of the sphingosine 1-phosphate degradation pathway.

            Sphingosine 1-phosphate (S1P) functions not only as a bioactive lipid molecule, but also as an important intermediate of the sole sphingolipid-to-glycerolipid metabolic pathway. However, the precise reactions and the enzymes involved in this pathway remain unresolved. We report here that yeast HFD1 and the Sjögren-Larsson syndrome (SLS)-causative mammalian gene ALDH3A2 are responsible for conversion of the S1P degradation product hexadecenal to hexadecenoic acid. The absence of ALDH3A2 in CHO-K1 mutant cells caused abnormal metabolism of S1P/hexadecenal to ether-linked glycerolipids. Moreover, we demonstrate that yeast Faa1 and Faa4 and mammalian ACSL family members are acyl-CoA synthetases involved in the sphingolipid-to-glycerolipid metabolic pathway and that hexadecenoic acid accumulates in Δfaa1 Δfaa4 mutant cells. These results unveil the entire S1P metabolic pathway: S1P is metabolized to glycerolipids via hexadecenal, hexadecenoic acid, hexadecenoyl-CoA, and palmitoyl-CoA. From our results we propose a possibility that accumulation of the S1P metabolite hexadecenal contributes to the pathogenesis of SLS. Copyright © 2012 Elsevier Inc. All rights reserved.
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              Selective Enhancement of Insulin Sensitivity in the Mature Adipocyte is Sufficient for Systemic Metabolic Improvements

              Dysfunctional adipose tissue represents a hallmark of type 2 diabetes and systemic insulin resistance, characterized by fibrotic deposition of collagens and increased immune cell infiltration within the depots. Here we generate an inducible model of loss of function of the protein phosphatase and tensin homolog (PTEN), a phosphatase critically involved in turning off the insulin signal transduction cascade, to assess the role of enhanced insulin signaling specifically in mature adipocytes. These mice gain more weight on chow diet and short-term as well as long-term high-fat diet exposure. Despite the increase in weight, they retain enhanced insulin sensitivity, show improvements in oral glucose tolerance tests, display reduced adipose tissue inflammation and maintain elevated adiponectin levels. These improvements also lead to reduced hepatic steatosis and enhanced hepatic insulin sensitivity. Prolonging insulin action selectively in the mature adipocyte is therefore sufficient to maintain normal systemic metabolic homeostasis.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                28 November 2019
                December 2019
                : 10
                : 12
                : 981
                Affiliations
                [1 ]College of Animal Science and Technology, Northwest A&F University, Yangling 712100, Shaanxi, China; lcc20151120@ 123456nwafu.edu.cn (C.L.); lianning110.119@ 123456163.com (A.L.); haiderraza110@ 123456nwafu.edu.cn (S.H.A.R.); rajwalikhan@ 123456nwafu.edu.cn (R.K.); 2014050493@ 123456nwsuaf.edu.com (X.W.); sihumeng@ 123456126.com (S.W.); eywangguohua@ 123456126.com (G.W.); zhangyu147258@ 123456nwafu.edu.cn (Y.Z.)
                [2 ]National Beef Cattle Improvement Center, Northwest A&F University, Yangling 712100, Shaanxi, China
                Author notes
                [* ]Correspondence: zanlinsen@ 123456163.com ; Tel.: +86-2987-091-923
                Author information
                https://orcid.org/0000-0002-6188-2911
                https://orcid.org/0000-0002-0961-1911
                https://orcid.org/0000-0001-5191-3457
                Article
                genes-10-00981
                10.3390/genes10120981
                6947481
                31795267
                c19a5ec0-82c2-4a4f-a5e4-910d51e9cc34
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 November 2019
                : 26 November 2019
                Categories
                Article

                fam13a,acsl1,ascl2,promoter,carcass quality,preadipocytes
                fam13a, acsl1, ascl2, promoter, carcass quality, preadipocytes

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