Advertisement

Gender differences in medium-chain dicarboxylic aciduria in alcoholic men and women

      Abstract

      PURPOSE: Women appear to be more vulnerable to developing alcoholic liver disease than men. In rats, we previously found that the response of certain pathways of fatty acid metabolism to alcohol feeding was less efficient in females than in males, resulting in striking accumulation of fatty acids in the liver of the female rats. We sought to determine whether similar differences occurred in humans.
      PATIENTS AND METHODS: Urinary excretion of medium chain (C6-C10) dicarboxylic acids (final products of fatty acid ω-oxidation) was determined in 40 recently drinking alcoholic subjects (24 men and 16 women) and 21 nonalcoholic subjects (12 men and nine women). Sebacic (C10), suberic (C8), and adipic (C6) acids were measured in urine by gas chromatography/mass spectrometry, and their excretion was expressed per mg of creatinine.
      RESULTS: In nonalcoholic subjects, there was no gender difference in dicarboxylic aciduria. By contrast, alcoholic men (but not alcoholic women) developed dicarboxylic hyperaciduria. Alcoholic men had a marked increase in adipic acid excretion and in the adipic/sebacic (C6/C10) ratio (an index of peroxisomal β-oxidation), whereas the values in alcoholic women did not differ from those in nonalcoholic women.
      CONCLUSIONS: The lack of response in alcoholic women could contribute to an aggravation of liver injury by promoting deleterious accumulation of fatty acids.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ashley M.J
        • Olin J.S
        • Harding le Riche W
        • Kornaczewski A
        • Schmidt W
        • Rankin J.G
        Morbidity in alcoholics. Evidence for accelerated development of physical disease in women.
        Arch Int Med. 1977; 137: 883-887
        • Morgan M.Y
        • Sherlock S
        Sex-related differences among 100 patients with alcoholic liver disease.
        BMJ. 1977; 1: 939-941
        • Lieber C.S
        Gender differences in alcohol metabolism and susceptibility.
        in: Wilsnak R.W Whitfield J.B Gender and Alcohol. Rutgers Center of Alcohol Studies, Piscataway, NJ1997: 77-89
      1. Jones BM, Jones MK. Male and female intoxication levels for three alcohol doses or do women really get higher than men? Alcohol Technical Report 1976;5:544–583.

        • Frezza M
        • DiPadova C
        • Pozzato G
        • Terpin M
        • Baraona E
        • Lieber C.S
        High blood alcohol levels in women.
        N EJM. 1990; 322: 95-99
        • Mishra L
        • Sharma S
        • Potter J.J
        • Mezey E
        More rapid elimination of alcohol in women as compared to their male siblings.
        Alcoholism: Clin Exp Res. 1989; 13: 752-754
        • Eriksson C.J.P
        • Fukunaga T
        • Sarkola T
        • Linholm H
        • Ahola L
        Estrogen-related acetaldehyde elevation in women during alcohol intoxication.
        Alcoholism: Clin Exp Res. 1996; 20: 1192-1195
        • Shevchuk O
        • Baraona E
        • Ma X.-L
        • Pignon J.-P
        • Lieber C.S
        Gender difference in the response of hepatic fatty acids and cytosolic fatty acid-binding capacity to alcohol consumption in rats.
        Proc Soc Exp Biol Med. 1991; 198: 584-590
        • Ma X.L
        • Baraona E
        • Lieber C.S
        Alcohol consumption enhances fatty acid ω-oxidation, with a greater increase in male than in female rats.
        Hepatology. 1993; 18: 1247-1253
        • Kaikaus R.M
        • Chan W.K
        • Ortiz de Montellano P.R
        • Bass N.M
        Mechanisms of regulation of liver fatty acid-binding protein.
        Mol Cell Biochem. 1993; 123: 93-100
        • Mishkin S
        • Turcotte R
        Stimulation of monoacylglycerophosphate formation by Z protein.
        Biochem Biophys Res Comm. 1974; 60: 376-381
        • O’Doherty P.J.A
        • Kuksis A
        Stimulation of triacylglycerol synthesis by Z protein in rat liver and intestinal mucosa.
        FEBS Lett. 1975; 60: 256-258
        • Burnett D.A
        • Lysenko N
        • Manning J.A
        • Ockner R.K
        Utilization of long chain fatty acids by rat liver.
        Gastroenterology. 1979; 77: 241-249
        • Mavrelis P.G
        • Ammon H.V
        • Gleysteen J.J
        • Komorowski R.A
        • Charaf U.K
        Hepatic free fatty acids in alcoholic liver disease and morbid obesity.
        Hepatology. 1983; 3: 226-231
      2. Mortensen P.B. Mechanisms of dicarboxylic aciduria and dicarboxylic acid metabolism. In: Kay Tanaka, ed. Fatty Acid Oxidation:Clinical, Biochemical and Molecular Aspects. Alan R. Liss, 1990;249–264.

        • Heinegârd D
        • Tiderström G
        Determination of serum creatinine by a direct colorimetric method.
        Clin Chim Acta. 1973; 43: 305-310
        • Tanaka K
        • Hine D.G
        • West-Dull A
        • Lynn T.B
        Gas-chromatographic method of analysis for urinary organic acids. I. Retention indices of 155 metabolically important compounds.
        Clin Chem. 1980; 26: 1839-1846
        • Tanaka K
        • West-Dull A
        • Hines D.G
        • Lynn T.B
        • Lowe T
        Gas-chromatographic method of analysis for urinary organic acids. II. Description of the procedure, and its application to diagnosis of patients with organic acidurias.
        Clin Chem. 1980; 26: 1847-1853
        • Tonsgard J.H
        Urinary dicarboxylic acids in Reye syndrome.
        J Pediatrics. 1985; 107: 79-84
        • Kundu R.K
        • Tonsgard J.H
        • Getz G.S
        Induction of omega-oxidation of monocarboxylic acids in rats by acetylsalicylic acid.
        J Clin Invest. 1991; 88: 1865-1872
        • Cederbaum A.L
        • Lieber C.S
        • Beattie D.S
        • Rubin E
        Effect of chronic ethanol ingestion on fatty acid oxidation by hepatic mitochondria.
        J Biol Chem. 1975; 250: 5122-5129
        • Ontko J.A
        Effects of ethanol on the metabolism of free fatty acids in isolated liver cells.
        J Lipid Res. 1973; 14: 78-86
        • Lieber C.S
        Cytochrome P-4502E1.
        Physiol Rev. 1997; 77: 517-544
        • Amet Y
        • Berthou F
        • Goasduff T
        • Salaun J.P
        • Le Breton L
        • Menez J.F
        Evidence that cytochrome P450 2E1 is involved in the (ω-1)-hydroxylation of lauric acid in rat liver microsomes.
        Biochem Biophys Res Comm. 1994; 203: 1168-1174
        • Boleda M.D
        • Saubi N
        • Farrés J
        • Parés X
        Physiological substrates for rat alcohol dehydrogenase classes.
        Arch Biochem Biophys. 1993; 307: 85-90
        • Rubin E
        • Lieber C.S
        Early fine structural changes in the human liver induced by alcohol.
        Gastroenterology. 1967; 52: 1-13
        • Spritz N
        • Lieber C.S
        Decrease of ethanol-induced fatty liver by ethyl α-p-chlorophenoxyisobutyrate.
        Proc Soc Exp Biol Med. 1966; 121: 147-149