Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets

Stephen D. Turley, Margrit Schwarz, David K. Spady, John M. Dietschy

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

These studies were undertaken to determine whether in young adult outbred CD-1 mice there were any gender-related differences in basal bile acid metabolism that might be important in determining how males and females in this species responded to a dietary cholesterol challenge. When fed a plain cereal-based rodent diet without added cholesterol, 3-month-old females, compared with age-matched males, manifested a significantly larger bile acid pool (89.1 vs. 54.1 μmol/100 g body weight), a higher rate of fecal bile acid excretion (13.6 vs. 8.5 μmol/d/100 g body weight), a more efficient level of intestinal cholesterol absorption (41.1% vs. 25.3%), and a lower rate of hepatic sterol synthesis (338 vs. 847 nmol/h/g). Similar results were found in C57BL/6 and 129Sv inbred mice. In matching groups of CD-1 mice fed a diet containing 1% cholesterol for 21 days, hepatic cholesterol levels increased much more in the females (from 2.4 to 9.1 mg/g) than in the males (from 2.1 to 5.2 mg/g). This occurred even though the level of stimulation of cholesterol 7α-hydroxylase activity in the females (79%) exceeded that in the males (55%), as did the magnitude of the increase in fecal bile acid excretion (females: 262% vs. males: 218%). However, in both sexes, bile acid pool size expanded only modestly and by a comparable degree (females: 19% vs. males: 26%) so that in the cholesterol-fed groups, the pool remained substantially larger in the females than in the males (102.3 vs. 67.6 μmol/100 g body weight). Together, these data demonstrate that while male and female CD-1 mice do not differ qualitatively in the way cholesterol feeding changes their bile acid metabolism, the inherently larger bile acid pool in the female likely facilitates the delivery of significantly more dietary cholesterol to the liver than is the case in males, thereby resulting in higher steady-state hepatic cholesterol levels.

Original languageEnglish (US)
Pages (from-to)1088-1094
Number of pages7
JournalHepatology
Volume28
Issue number4 I
DOIs
StatePublished - 1998

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Sterols
Bile Acids and Salts
Cholesterol
Diet
Dietary Cholesterol
Liver
Body Weight
Cholesterol 7-alpha-Hydroxylase
Intestinal Absorption
Young Adult
Rodentia

ASJC Scopus subject areas

  • Hepatology

Cite this

Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets. / Turley, Stephen D.; Schwarz, Margrit; Spady, David K.; Dietschy, John M.

In: Hepatology, Vol. 28, No. 4 I, 1998, p. 1088-1094.

Research output: Contribution to journalArticle

Turley, Stephen D. ; Schwarz, Margrit ; Spady, David K. ; Dietschy, John M. / Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets. In: Hepatology. 1998 ; Vol. 28, No. 4 I. pp. 1088-1094.
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abstract = "These studies were undertaken to determine whether in young adult outbred CD-1 mice there were any gender-related differences in basal bile acid metabolism that might be important in determining how males and females in this species responded to a dietary cholesterol challenge. When fed a plain cereal-based rodent diet without added cholesterol, 3-month-old females, compared with age-matched males, manifested a significantly larger bile acid pool (89.1 vs. 54.1 μmol/100 g body weight), a higher rate of fecal bile acid excretion (13.6 vs. 8.5 μmol/d/100 g body weight), a more efficient level of intestinal cholesterol absorption (41.1{\%} vs. 25.3{\%}), and a lower rate of hepatic sterol synthesis (338 vs. 847 nmol/h/g). Similar results were found in C57BL/6 and 129Sv inbred mice. In matching groups of CD-1 mice fed a diet containing 1{\%} cholesterol for 21 days, hepatic cholesterol levels increased much more in the females (from 2.4 to 9.1 mg/g) than in the males (from 2.1 to 5.2 mg/g). This occurred even though the level of stimulation of cholesterol 7α-hydroxylase activity in the females (79{\%}) exceeded that in the males (55{\%}), as did the magnitude of the increase in fecal bile acid excretion (females: 262{\%} vs. males: 218{\%}). However, in both sexes, bile acid pool size expanded only modestly and by a comparable degree (females: 19{\%} vs. males: 26{\%}) so that in the cholesterol-fed groups, the pool remained substantially larger in the females than in the males (102.3 vs. 67.6 μmol/100 g body weight). Together, these data demonstrate that while male and female CD-1 mice do not differ qualitatively in the way cholesterol feeding changes their bile acid metabolism, the inherently larger bile acid pool in the female likely facilitates the delivery of significantly more dietary cholesterol to the liver than is the case in males, thereby resulting in higher steady-state hepatic cholesterol levels.",
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