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TSC22D4 is a molecular output of hepatic wasting metabolism.

Jones A, Friedrich K, Rohm M, Schäfer M, Algire C, Kulozik P, Seibert O, Müller-Decker K, Sijmonsma T, Strzoda D, Sticht C, Gretz N, Dallinga-Thie GM, Leuchs B, Kögl M, Stremmel W, Diaz MB, Herzig S - EMBO Mol Med (2013)

Bottom Line: In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis.As a molecular cachexia output pathway, hepatic levels of the transcription factor transforming growth factor beta 1-stimulated clone (TSC) 22 D4 were increased in cancer cachexia.Therefore, hepatic TSC22D4 activity may represent a molecular rationale for peripheral energy deprivation in subjects with metabolic wasting diseases, including cancer cachexia.

View Article: PubMed Central - PubMed

Affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance, Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.

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TSC22D4 is induced in experimental wasting conditionsQuantitative PCR analysis of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a), Peroxisome proliferator-activated receptor gamma coactivator 1-beta (Pgc1b), Nuclear receptor coactivator 1 (Src1), nuclear receptor coactivator 3 (Src3), Transducin beta like 1 (Tbl1), Creb binding protein (Cbp) and Tsc22 domain family member 3 (Tsc22d3) in Balb/C mice injected with either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6). Statistical test: Student's t-test.Western blot analysis of TSC22D4 and valosine-containing protein (VCP) expression in representative mice from A.Serum TG levels in C57Bl/6 mice fed a methionine and choline deficient diet (MCD) or a corresponding control diet for 4 weeks (means ± SEM, n ≥ 5).Quantitative PCR analysis of fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebp1) RNA levels in the same mice as in C.Quantitative PCR analysis of Tsc22 domain family member 4 (Tsc22d4) RNA levels in the same mice as in C.Western blot analysis of TSC22D4 and VCP expression in representative mice from C. Statistical test C–E: Student's t-test.
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fig03: TSC22D4 is induced in experimental wasting conditionsQuantitative PCR analysis of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a), Peroxisome proliferator-activated receptor gamma coactivator 1-beta (Pgc1b), Nuclear receptor coactivator 1 (Src1), nuclear receptor coactivator 3 (Src3), Transducin beta like 1 (Tbl1), Creb binding protein (Cbp) and Tsc22 domain family member 3 (Tsc22d3) in Balb/C mice injected with either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6). Statistical test: Student's t-test.Western blot analysis of TSC22D4 and valosine-containing protein (VCP) expression in representative mice from A.Serum TG levels in C57Bl/6 mice fed a methionine and choline deficient diet (MCD) or a corresponding control diet for 4 weeks (means ± SEM, n ≥ 5).Quantitative PCR analysis of fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebp1) RNA levels in the same mice as in C.Quantitative PCR analysis of Tsc22 domain family member 4 (Tsc22d4) RNA levels in the same mice as in C.Western blot analysis of TSC22D4 and VCP expression in representative mice from C. Statistical test C–E: Student's t-test.

Mentions: Gene expression analysis revealed no obvious differences in mRNA levels for transcriptional co-factors PGC-1alpha/beta, SRC1, SRC3, TBL1 and CBP in cachectic livers, whilst GILZ was downregulated (Fig 3A). In contrast, both mRNA as well as protein levels of leucine zipper transcription factor TSC22D4 were found to be induced in livers of tumour-bearing, cachectic mice as compared with healthy control littermates (Fig 3B, Supporting Information Fig S2A), demonstrating that tumour-associated energy wasting is tightly and specifically associated with elevated TSC22D4 expression in the liver.


TSC22D4 is a molecular output of hepatic wasting metabolism.

Jones A, Friedrich K, Rohm M, Schäfer M, Algire C, Kulozik P, Seibert O, Müller-Decker K, Sijmonsma T, Strzoda D, Sticht C, Gretz N, Dallinga-Thie GM, Leuchs B, Kögl M, Stremmel W, Diaz MB, Herzig S - EMBO Mol Med (2013)

TSC22D4 is induced in experimental wasting conditionsQuantitative PCR analysis of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a), Peroxisome proliferator-activated receptor gamma coactivator 1-beta (Pgc1b), Nuclear receptor coactivator 1 (Src1), nuclear receptor coactivator 3 (Src3), Transducin beta like 1 (Tbl1), Creb binding protein (Cbp) and Tsc22 domain family member 3 (Tsc22d3) in Balb/C mice injected with either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6). Statistical test: Student's t-test.Western blot analysis of TSC22D4 and valosine-containing protein (VCP) expression in representative mice from A.Serum TG levels in C57Bl/6 mice fed a methionine and choline deficient diet (MCD) or a corresponding control diet for 4 weeks (means ± SEM, n ≥ 5).Quantitative PCR analysis of fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebp1) RNA levels in the same mice as in C.Quantitative PCR analysis of Tsc22 domain family member 4 (Tsc22d4) RNA levels in the same mice as in C.Western blot analysis of TSC22D4 and VCP expression in representative mice from C. Statistical test C–E: Student's t-test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3569644&req=5

fig03: TSC22D4 is induced in experimental wasting conditionsQuantitative PCR analysis of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1a), Peroxisome proliferator-activated receptor gamma coactivator 1-beta (Pgc1b), Nuclear receptor coactivator 1 (Src1), nuclear receptor coactivator 3 (Src3), Transducin beta like 1 (Tbl1), Creb binding protein (Cbp) and Tsc22 domain family member 3 (Tsc22d3) in Balb/C mice injected with either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6). Statistical test: Student's t-test.Western blot analysis of TSC22D4 and valosine-containing protein (VCP) expression in representative mice from A.Serum TG levels in C57Bl/6 mice fed a methionine and choline deficient diet (MCD) or a corresponding control diet for 4 weeks (means ± SEM, n ≥ 5).Quantitative PCR analysis of fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebp1) RNA levels in the same mice as in C.Quantitative PCR analysis of Tsc22 domain family member 4 (Tsc22d4) RNA levels in the same mice as in C.Western blot analysis of TSC22D4 and VCP expression in representative mice from C. Statistical test C–E: Student's t-test.
Mentions: Gene expression analysis revealed no obvious differences in mRNA levels for transcriptional co-factors PGC-1alpha/beta, SRC1, SRC3, TBL1 and CBP in cachectic livers, whilst GILZ was downregulated (Fig 3A). In contrast, both mRNA as well as protein levels of leucine zipper transcription factor TSC22D4 were found to be induced in livers of tumour-bearing, cachectic mice as compared with healthy control littermates (Fig 3B, Supporting Information Fig S2A), demonstrating that tumour-associated energy wasting is tightly and specifically associated with elevated TSC22D4 expression in the liver.

Bottom Line: In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis.As a molecular cachexia output pathway, hepatic levels of the transcription factor transforming growth factor beta 1-stimulated clone (TSC) 22 D4 were increased in cancer cachexia.Therefore, hepatic TSC22D4 activity may represent a molecular rationale for peripheral energy deprivation in subjects with metabolic wasting diseases, including cancer cachexia.

View Article: PubMed Central - PubMed

Affiliation: Joint Division Molecular Metabolic Control, DKFZ-ZMBH Alliance, Network Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Center for Molecular Biology (ZMBH) and University Hospital, Heidelberg University, Heidelberg, Germany.

Show MeSH
Related in: MedlinePlus