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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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Cachectic mice display impaired hepatic VLDL secretion and hypobetalipoproteinemiaHepatic VLDL release in Balb/C mice injected either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6, Two Way Repeated Measures ANOVA, Holm-Sidak post hoc).Clearance of human ApoB from serum of Balb/C mice injected with either PBS or 1.5 × 106 C26 cells. 20 µg of human VLDL were injected into each animal and serum samples were taken at the indicated time points. Human ApoB levels were determined by human-specific ELISA (means ± SEM, n = 2–4).Quantitative PCR analysis of hepatic ATP citrate lyase (Acly), fatty acid synthase (Fasn) and stearoyl-CoA desaturase-1 (Scd1) RNA levels in the same mice as in A (Student's t-test).Lipoprotein-associated serum TG levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.Lipoprotein-associated serum cholesterol levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.
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fig02: Cachectic mice display impaired hepatic VLDL secretion and hypobetalipoproteinemiaHepatic VLDL release in Balb/C mice injected either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6, Two Way Repeated Measures ANOVA, Holm-Sidak post hoc).Clearance of human ApoB from serum of Balb/C mice injected with either PBS or 1.5 × 106 C26 cells. 20 µg of human VLDL were injected into each animal and serum samples were taken at the indicated time points. Human ApoB levels were determined by human-specific ELISA (means ± SEM, n = 2–4).Quantitative PCR analysis of hepatic ATP citrate lyase (Acly), fatty acid synthase (Fasn) and stearoyl-CoA desaturase-1 (Scd1) RNA levels in the same mice as in A (Student's t-test).Lipoprotein-associated serum TG levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.Lipoprotein-associated serum cholesterol levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.

Mentions: Consistent with the hypothesis that cancer cachexia specifically disrupts the efficient mobilization and/or shift from intra-hepatic to serum TG pools, C26 mice showed significantly decreased hepatic VLDL secretion as compared with non-tumour-bearing littermates (Fig 2A), while hepatic ApoB uptake capacity from the serum was slightly impaired (Fig 2B). In congruence with the impaired hepatic VLDL secretion rate under cachectic conditions, tumour-bearing animals showed significant downregulation of genes in the lipogenic pathway in the liver as compared with healthy controls, thereby impairing substrate provision for the VLDL assembly pathway (Fig 2C; Elam et al, 2001; Moon et al, 2011).


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)

Cachectic mice display impaired hepatic VLDL secretion and hypobetalipoproteinemiaHepatic VLDL release in Balb/C mice injected either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6, Two Way Repeated Measures ANOVA, Holm-Sidak post hoc).Clearance of human ApoB from serum of Balb/C mice injected with either PBS or 1.5 × 106 C26 cells. 20 µg of human VLDL were injected into each animal and serum samples were taken at the indicated time points. Human ApoB levels were determined by human-specific ELISA (means ± SEM, n = 2–4).Quantitative PCR analysis of hepatic ATP citrate lyase (Acly), fatty acid synthase (Fasn) and stearoyl-CoA desaturase-1 (Scd1) RNA levels in the same mice as in A (Student's t-test).Lipoprotein-associated serum TG levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.Lipoprotein-associated serum cholesterol levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Cachectic mice display impaired hepatic VLDL secretion and hypobetalipoproteinemiaHepatic VLDL release in Balb/C mice injected either PBS or 1.5 × 106 C26 cells (means ± SEM, n ≥ 6, Two Way Repeated Measures ANOVA, Holm-Sidak post hoc).Clearance of human ApoB from serum of Balb/C mice injected with either PBS or 1.5 × 106 C26 cells. 20 µg of human VLDL were injected into each animal and serum samples were taken at the indicated time points. Human ApoB levels were determined by human-specific ELISA (means ± SEM, n = 2–4).Quantitative PCR analysis of hepatic ATP citrate lyase (Acly), fatty acid synthase (Fasn) and stearoyl-CoA desaturase-1 (Scd1) RNA levels in the same mice as in A (Student's t-test).Lipoprotein-associated serum TG levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.Lipoprotein-associated serum cholesterol levels as measured by fast protein liquid chromatography (FPLC) in the same mice as in A.
Mentions: Consistent with the hypothesis that cancer cachexia specifically disrupts the efficient mobilization and/or shift from intra-hepatic to serum TG pools, C26 mice showed significantly decreased hepatic VLDL secretion as compared with non-tumour-bearing littermates (Fig 2A), while hepatic ApoB uptake capacity from the serum was slightly impaired (Fig 2B). In congruence with the impaired hepatic VLDL secretion rate under cachectic conditions, tumour-bearing animals showed significant downregulation of genes in the lipogenic pathway in the liver as compared with healthy controls, thereby impairing substrate provision for the VLDL assembly pathway (Fig 2C; Elam et al, 2001; Moon et al, 2011).

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