The Experts below are selected from a list of 152997 Experts worldwide ranked by ideXlab platform
Friedhelm Schroeder - One of the best experts on this subject based on the ideXlab platform.
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Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic Phytol metabolism
Archives of biochemistry and biophysics, 2017Co-Authors: Avery L. Mcintosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm SchroederAbstract:Abstract While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic Phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% Phytol. GC/MS showed that hepatic: i) Phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of Phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary Phytol in WT females, but only slightly in WT males; iii) accumulation of Phytol and BCFA was further increased by DKO in Phytol-fed females, but much more markedly in males. Livers of Phytol-fed WT female mice as well as Phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver Phytol accumulation was not due to increased SCP-2 binding/transport of Phytol since SCP-2 bound phytanic acid, but not its precursor Phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary Phytol and BCFA.
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Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic Phytol metabolism in mice.
Journal of lipid research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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impact of fabp1 scp 2 scp x gene ablation tko on hepatic Phytol metabolism in mice
Journal of Lipid Research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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Phytol induced hepatotoxicity in mice
Toxicologic pathology, 2009Co-Authors: John T. Mackie, Avery L. Mcintosh, Friedhelm Schroeder, Barbara P. Atshaves, H. Ross Payne, Ann B. KierAbstract:Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of Phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor a (PPARa) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary Phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARa-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5% Phytol and male and female mice fed 1% Phytol exhibited midzonal hepatocellular necrosis, periportal hepatocellular fatty vacuolation, and corresponding increases in liver levels of the Phytol metabolites phytanic acid and pristanic acid. Hepatic expression of sterol carrier protein-x (SCP-x) was five- to twelve-fold lower in female mice than in male mice. These results suggest that Phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x.
Avery L. Mcintosh - One of the best experts on this subject based on the ideXlab platform.
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Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic Phytol metabolism
Archives of biochemistry and biophysics, 2017Co-Authors: Avery L. Mcintosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm SchroederAbstract:Abstract While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic Phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% Phytol. GC/MS showed that hepatic: i) Phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of Phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary Phytol in WT females, but only slightly in WT males; iii) accumulation of Phytol and BCFA was further increased by DKO in Phytol-fed females, but much more markedly in males. Livers of Phytol-fed WT female mice as well as Phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver Phytol accumulation was not due to increased SCP-2 binding/transport of Phytol since SCP-2 bound phytanic acid, but not its precursor Phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary Phytol and BCFA.
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Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic Phytol metabolism in mice.
Journal of lipid research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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impact of fabp1 scp 2 scp x gene ablation tko on hepatic Phytol metabolism in mice
Journal of Lipid Research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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Phytol induced hepatotoxicity in mice
Toxicologic pathology, 2009Co-Authors: John T. Mackie, Avery L. Mcintosh, Friedhelm Schroeder, Barbara P. Atshaves, H. Ross Payne, Ann B. KierAbstract:Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of Phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor a (PPARa) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary Phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARa-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5% Phytol and male and female mice fed 1% Phytol exhibited midzonal hepatocellular necrosis, periportal hepatocellular fatty vacuolation, and corresponding increases in liver levels of the Phytol metabolites phytanic acid and pristanic acid. Hepatic expression of sterol carrier protein-x (SCP-x) was five- to twelve-fold lower in female mice than in male mice. These results suggest that Phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x.
Ann B. Kier - One of the best experts on this subject based on the ideXlab platform.
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Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic Phytol metabolism
Archives of biochemistry and biophysics, 2017Co-Authors: Avery L. Mcintosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm SchroederAbstract:Abstract While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic Phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% Phytol. GC/MS showed that hepatic: i) Phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of Phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary Phytol in WT females, but only slightly in WT males; iii) accumulation of Phytol and BCFA was further increased by DKO in Phytol-fed females, but much more markedly in males. Livers of Phytol-fed WT female mice as well as Phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver Phytol accumulation was not due to increased SCP-2 binding/transport of Phytol since SCP-2 bound phytanic acid, but not its precursor Phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary Phytol and BCFA.
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Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic Phytol metabolism in mice.
Journal of lipid research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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impact of fabp1 scp 2 scp x gene ablation tko on hepatic Phytol metabolism in mice
Journal of Lipid Research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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Phytol induced hepatotoxicity in mice
Toxicologic pathology, 2009Co-Authors: John T. Mackie, Avery L. Mcintosh, Friedhelm Schroeder, Barbara P. Atshaves, H. Ross Payne, Ann B. KierAbstract:Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of Phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor a (PPARa) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary Phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARa-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5% Phytol and male and female mice fed 1% Phytol exhibited midzonal hepatocellular necrosis, periportal hepatocellular fatty vacuolation, and corresponding increases in liver levels of the Phytol metabolites phytanic acid and pristanic acid. Hepatic expression of sterol carrier protein-x (SCP-x) was five- to twelve-fold lower in female mice than in male mice. These results suggest that Phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x.
Stephen M. Storey - One of the best experts on this subject based on the ideXlab platform.
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Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic Phytol metabolism
Archives of biochemistry and biophysics, 2017Co-Authors: Avery L. Mcintosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm SchroederAbstract:Abstract While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic Phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% Phytol. GC/MS showed that hepatic: i) Phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of Phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary Phytol in WT females, but only slightly in WT males; iii) accumulation of Phytol and BCFA was further increased by DKO in Phytol-fed females, but much more markedly in males. Livers of Phytol-fed WT female mice as well as Phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver Phytol accumulation was not due to increased SCP-2 binding/transport of Phytol since SCP-2 bound phytanic acid, but not its precursor Phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary Phytol and BCFA.
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Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic Phytol metabolism in mice.
Journal of lipid research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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impact of fabp1 scp 2 scp x gene ablation tko on hepatic Phytol metabolism in mice
Journal of Lipid Research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
Huan Huang - One of the best experts on this subject based on the ideXlab platform.
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Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic Phytol metabolism
Archives of biochemistry and biophysics, 2017Co-Authors: Avery L. Mcintosh, Stephen M. Storey, Huan Huang, Ann B. Kier, Friedhelm SchroederAbstract:Abstract While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic Phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% Phytol. GC/MS showed that hepatic: i) Phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of Phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary Phytol in WT females, but only slightly in WT males; iii) accumulation of Phytol and BCFA was further increased by DKO in Phytol-fed females, but much more markedly in males. Livers of Phytol-fed WT female mice as well as Phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver Phytol accumulation was not due to increased SCP-2 binding/transport of Phytol since SCP-2 bound phytanic acid, but not its precursor Phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary Phytol and BCFA.
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Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic Phytol metabolism in mice.
Journal of lipid research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
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impact of fabp1 scp 2 scp x gene ablation tko on hepatic Phytol metabolism in mice
Journal of Lipid Research, 2017Co-Authors: Stephen M. Storey, Avery L. Mcintosh, Huan Huang, Ann B. Kier, Gregory G. Martin, Friedhelm SchroederAbstract:Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary Phytol. However, interpretation of physiological function in mice singly gene ablated in the Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound Phytol, but both had high affinity for its metabolite, phytanic acid; ii) GC-MS studies with Phytol-fed WT and Fabp1/Scp-2/SCP-x gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of Phytol metabolites in vivo in females and less so in males. Concomitantly, dietary Phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary Phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary Phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: 1) SCP-2 and FABP1 both facilitated Phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic Phytol metabolism than FABP1.
