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Gender-divergent profile of bile acid homeostasis during aging of mice.

Fu ZD, Csanaky IL, Klaassen CD - PLoS ONE (2012)

Bottom Line: Aging is a physiological process with a progressive decline of adaptation and functional capacity of the body.Bile acids (BAs) have been recognized as signaling molecules regulating the homeostasis of glucose, lipid, and energy.In female mice, (1) the mRNAs of hepatic BA uptake transporters, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) and the organic anion transporting polypeptide 1b2 (Oatp1b2), decreased after 12 months, and similar trends were observed for their proteins; (2) the mRNA of the rate-limiting enzyme for BA synthesis, cholesterol 7α-hydroxylase (Cyp7a1), increased from 3 to 9 months and remained high thereafter.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, United States of America.

ABSTRACT
Aging is a physiological process with a progressive decline of adaptation and functional capacity of the body. Bile acids (BAs) have been recognized as signaling molecules regulating the homeostasis of glucose, lipid, and energy. The current study characterizes the age-related changes of individual BA concentrations by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in serum and liver of male and female C57BL/6 mice from 3 to 27 months of age. Total BA concentrations in serum increased 340% from 3 to 27 months in female mice, whereas they remained relatively constant with age in male mice. During aging, male and female mice shared the following changes: (1) BA concentrations in liver remained relatively constant; (2) the proportions of beta-muricholic acid (βMCA) increased and deoxycholic acid (DCA) decreased between 3 and 27 months in serum and liver; and (3) total BAs in serum and liver became more hydrophilic between 3 and 27 months. In female mice, (1) the mRNAs of hepatic BA uptake transporters, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) and the organic anion transporting polypeptide 1b2 (Oatp1b2), decreased after 12 months, and similar trends were observed for their proteins; (2) the mRNA of the rate-limiting enzyme for BA synthesis, cholesterol 7α-hydroxylase (Cyp7a1), increased from 3 to 9 months and remained high thereafter. However, in male mice, Ntcp, Oatp1b2, and Cyp7a1 mRNAs remained relatively constant with age. In summary, the current study shows gender-divergent profiles of BA concentrations and composition in serum and liver of mice during aging, which is likely due to the gender-divergent expression of BA transporters Ntcp and Oatp1b2 as well as the synthetic enzyme Cyp7a1.

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Total BA concentrations in serum during aging of male and female mice.Data are presented as means ± SEM of 5–7 mice. Daggers (†) represent statistically significant difference from the value at 3 months of age during aging of male mice. Double daggers (‡) represent statistically significant difference from the value at 3 months of age during aging of female mice. Age-dependent differences were considered at p<0.05 by one-way ANOVA, followed by Duncan's post-hoc test. Asterisks (*) represent statistically significant difference between male and female mice at respective ages during aging (p<0.05), by student t-test.
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pone-0032551-g002: Total BA concentrations in serum during aging of male and female mice.Data are presented as means ± SEM of 5–7 mice. Daggers (†) represent statistically significant difference from the value at 3 months of age during aging of male mice. Double daggers (‡) represent statistically significant difference from the value at 3 months of age during aging of female mice. Age-dependent differences were considered at p<0.05 by one-way ANOVA, followed by Duncan's post-hoc test. Asterisks (*) represent statistically significant difference between male and female mice at respective ages during aging (p<0.05), by student t-test.

Mentions: Total BA concentrations in serum remained relatively constant in male mice, whereas in female mice, they increased 340% from 3 to 27 months of age, due to an increase in both conjugated (280%) and unconjugated (400%) BAs (Fig. 2). Female mice had higher total BA concentrations than male mice from 9 (190%) to 27 (370%) months.


Gender-divergent profile of bile acid homeostasis during aging of mice.

Fu ZD, Csanaky IL, Klaassen CD - PLoS ONE (2012)

Total BA concentrations in serum during aging of male and female mice.Data are presented as means ± SEM of 5–7 mice. Daggers (†) represent statistically significant difference from the value at 3 months of age during aging of male mice. Double daggers (‡) represent statistically significant difference from the value at 3 months of age during aging of female mice. Age-dependent differences were considered at p<0.05 by one-way ANOVA, followed by Duncan's post-hoc test. Asterisks (*) represent statistically significant difference between male and female mice at respective ages during aging (p<0.05), by student t-test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293819&req=5

pone-0032551-g002: Total BA concentrations in serum during aging of male and female mice.Data are presented as means ± SEM of 5–7 mice. Daggers (†) represent statistically significant difference from the value at 3 months of age during aging of male mice. Double daggers (‡) represent statistically significant difference from the value at 3 months of age during aging of female mice. Age-dependent differences were considered at p<0.05 by one-way ANOVA, followed by Duncan's post-hoc test. Asterisks (*) represent statistically significant difference between male and female mice at respective ages during aging (p<0.05), by student t-test.
Mentions: Total BA concentrations in serum remained relatively constant in male mice, whereas in female mice, they increased 340% from 3 to 27 months of age, due to an increase in both conjugated (280%) and unconjugated (400%) BAs (Fig. 2). Female mice had higher total BA concentrations than male mice from 9 (190%) to 27 (370%) months.

Bottom Line: Aging is a physiological process with a progressive decline of adaptation and functional capacity of the body.Bile acids (BAs) have been recognized as signaling molecules regulating the homeostasis of glucose, lipid, and energy.In female mice, (1) the mRNAs of hepatic BA uptake transporters, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) and the organic anion transporting polypeptide 1b2 (Oatp1b2), decreased after 12 months, and similar trends were observed for their proteins; (2) the mRNA of the rate-limiting enzyme for BA synthesis, cholesterol 7α-hydroxylase (Cyp7a1), increased from 3 to 9 months and remained high thereafter.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, United States of America.

ABSTRACT
Aging is a physiological process with a progressive decline of adaptation and functional capacity of the body. Bile acids (BAs) have been recognized as signaling molecules regulating the homeostasis of glucose, lipid, and energy. The current study characterizes the age-related changes of individual BA concentrations by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in serum and liver of male and female C57BL/6 mice from 3 to 27 months of age. Total BA concentrations in serum increased 340% from 3 to 27 months in female mice, whereas they remained relatively constant with age in male mice. During aging, male and female mice shared the following changes: (1) BA concentrations in liver remained relatively constant; (2) the proportions of beta-muricholic acid (βMCA) increased and deoxycholic acid (DCA) decreased between 3 and 27 months in serum and liver; and (3) total BAs in serum and liver became more hydrophilic between 3 and 27 months. In female mice, (1) the mRNAs of hepatic BA uptake transporters, the Na(+)/taurocholate cotransporting polypeptide (Ntcp) and the organic anion transporting polypeptide 1b2 (Oatp1b2), decreased after 12 months, and similar trends were observed for their proteins; (2) the mRNA of the rate-limiting enzyme for BA synthesis, cholesterol 7α-hydroxylase (Cyp7a1), increased from 3 to 9 months and remained high thereafter. However, in male mice, Ntcp, Oatp1b2, and Cyp7a1 mRNAs remained relatively constant with age. In summary, the current study shows gender-divergent profiles of BA concentrations and composition in serum and liver of mice during aging, which is likely due to the gender-divergent expression of BA transporters Ntcp and Oatp1b2 as well as the synthetic enzyme Cyp7a1.

Show MeSH
Related in: MedlinePlus