Further studies on the role of bile salts in cholesterol esterification and absorption from the gut,☆☆

https://doi.org/10.1016/0003-9861(71)90182-2Get rights and content

Abstract

The object of this investigation was to study the effectiveness of varying amounts of taurocholate and of high doses of other unconjugated and conjugated bile salts on the appearance of 4-14C-cholesterol in the lymph. A preparation was used which consists of a modification of Bollman's technique for the cannulation of the abdominal thoracic duct in the rat; a uniform lymph flow rate was assured by infusion of isotonic saline at a constant rate into the duodenum.

Experimentally, individual unconjugated or conjugated bile salts were administered by stomach tube in an emulsion containing protein, carbohydrate, monoolein, and 4-14C-cholesterol. Lymph was collected hourly for at least 12 hr after feeding. The radioactivity of free cholesterol and cholesterol esters was analyzed in a liquid scintillation counter after separation by glass fiber paper chromatography.

The appearance of both dietary and endogenous cholesterol in the thoracic duct lymph, measured 6 hr after feeding, was related to the type of bile salt administered with the emulsion.

In experiments in which only a trace amount of 14-cholesterol was fed, the critical micellar concentration of taurocholate was produced by administration of 225 mg or more of the bile salt. Taurocholate supported the absorption of total cholesterol similarly to that observed with natural bile. In addition, taurocholate was the most effective bile salt in aiding cholesterol absorption. Glycocholate and glycodeoxycholate were significantly less effective than the corresponding taurine conjugates. Absorption was not enhanced by combining bile salts in various proportions as to make a total of 250 mg.

After administration of 3α,7α,12α-trihydroxy-5β-unconjugated and conjugated bile salts, 65–75% of the cholesterol in the lymph was found to be esterified. Both 3α, 12β-dihydroxy-5β- and 3α,7α-dihydroxy-5β-conjugated bile salts were capable of activating the absorption mechanism, but they supported the esterification of only 50% of the exogenous or endogenous cholesterol in the lymph. Esterified cholesterol almost disappears from the lymph of those animals dosed with taurodeoxycholate.

These findings have been interpreted as indicative that certain specific conjugated bile salts play a special role in the esterification of the sterol during intestinal absorption and that the appearance of unesterified and of esterified cholesterol in the lymph is the result of at least two independent mechanism.

After feeding the same emulsion with either natural bile, taurocholate, or glycocholate and a trace dose of oleic acid-9,10-3H, biphasic kinetics for the appearance of radioactive triglycerides in the lymph was demonstrated.

References (53)

  • S.K. Murthy et al.

    Biochim. Biophys. Acta

    (1963)
  • M.D. Siperstein et al.

    J. Biol. Chem

    (1952)
  • H.H. Hernandez et al.

    J. Biol. Chem

    (1957)
  • G.V. Vahouny et al.

    Biochem. Biophys. Res. Commun

    (1964)
  • G.V. Vahouny et al.

    Biochim. Biophys. Acta

    (1965)
  • G.V. Vahouny et al.

    Arch. Biochem. Biophys

    (1968)
  • H.E. Gallo-Torres et al.

    Biochim. Biophys. Acta

    (1969)
  • J.E. Muldrey et al.

    Anal. Biochem

    (1965)
  • J.G. Hamilton et al.

    Biochem. Biophys. Res. Commun

    (1961)
  • L.A. Baillie

    Int. J. Appl. Radiat. Isotop

    (1960)
  • F. Kern et al.

    Gastroenterology

    (1965)
  • B. Borgström

    J. Lipid Res

    (1968)
  • A.F. Hofmann

    Gastroenterology

    (1966)
  • L. Swell et al.

    J. Biol. Chem

    (1958)
  • J.R. Senior

    J. Lipid Res

    (1964)
  • C. Sylvén et al.

    J. Lipid Res

    (1969)
  • J.D. Wilson et al.

    J. Lipid Res

    (1968)
  • H.H. Hernandez et al.

    J. Biol. Chem

    (1954)
  • L. Swell et al.

    Arch. Biochem. Biophys

    (1962)
  • N.H. Bell et al.

    Amer. J. Clin. Nutr

    (1969)
  • E.G. Daskalakis et al.

    Arch. Biochem. Biophys

    (1955)
  • W.J. Simmonds

    Amer. J. Clin. Nutr

    (1969)
  • A. Karmen et al.

    J. Lipid Res

    (1963)
  • C.R. Treadwell et al.
  • De W.S. Goodman

    Physiol. Rev

    (1965)
  • C.R. Treadwell et al.
  • Cited by (23)

    • Efficient reabsorption of transintestinally excreted cholesterol is a strong determinant for cholesterol disposal in mice

      2019, Journal of Lipid Research
      Citation Excerpt :

      Together, these findings indicate that the abrogated intestinal cholesterol absorption in Asbt−/− mice primarily resulted from strongly reduced biliary BA secretion. Apparently, the decreased biliary BA secretion could not be compensated for by a more hydrophobic BA composition, despite the notion that hydrophobic BAs are more effective in aiding the micellar solubilization and subsequent absorption of cholesterol (40, 42). Theoretically, the decreased cholesterol absorption in Asbt−/− mice could be due to the downregulation of Npc1l1 expression in the duodenum, but the unaffected steady-state mRNA levels did not support this possibility (Fig. 5A).

    • Meta-analysis of the influence of dietary glycine and serine, with consideration of methionine and cysteine, on growth and feed conversion of broilers

      2015, Poultry Science
      Citation Excerpt :

      Furthermore, one molecule of Ser is required to synthesize one molecule of cysteine (Cys) from one molecule of methionine (Met) when L-homocysteine is metabolized to L,L-cystathione (Braunstein et al., 1969; Velíšek and Cejpek, 2006). Other metabolic pathways that require Gly or Ser are the synthesis of glutathione (Bartlett et al., 1956) and creatine (Bloch and Schoenheimer, 1940), bile activity (Gallo-Torres et al., 1971), and protein synthesis in the liver (Ngo et al., 1977). Numerous studies, in particular those investigating reduced-protein diets, have observed the performance-enhancing effects of Gly supplementation (e.g., Corzo et al., 2004; Dean et al., 2006; Jiang et al., 2005).

    View all citing articles on Scopus

    This work includes material from a thesis submitted by Hugo E. Gallo-Torres to the Graduate School of Tulane University in partial fulfillment of the requirements for the degree of Doctor of Philosophy. The research was supported by Grants-in-Aid TIAM 5369 and H 4150 from the National Institutes of Health, Bethesda, Maryland, and by a Grant from Hoffmann-La Roche Inc., Nutley, New Jersey.

    ☆☆

    Part of this work was presented at the Eighth International Congress of Nutrition, Prague, September 1969.

    3

    Present address: Department of Vitamin and Nutritional Research, Hoffmann-La Roche & Co., Basle, Switzerland.

    4

    Present address: Department of Biochemical Nutrition, Hoffmann-La Roche Inc., Nutley, New Jersey 07110.

    View full text