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Metabolism

Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women

  1. Marleen Kars1,
  2. Ling Yang2,
  3. Margaret F. Gregor2,
  4. B. Selma Mohammed1,
  5. Terri A. Pietka1,
  6. Brian N. Finck1,
  7. Bruce W. Patterson1,
  8. Jay D. Horton3,
  9. Bettina Mittendorfer1,
  10. Gökhan S. Hotamisligil2 and
  11. Samuel Klein1
  1. 1Center for Human Nutrition and Atkins Center of Excellence in Obesity Medicine, Washington University School of Medicine, St. Louis, Missouri;
  2. 2Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts;
  3. 3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
  1. Corresponding author: Samuel Klein, sklein{at}wustl.edu.
Diabetes 2010 Aug; 59(8): 1899-1905. https://doi.org/10.2337/db10-0308
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  • FIG. 1.
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    FIG. 1.

    Liver, muscle, and adipose tissue insulin sensitivity before (□) and after (Embedded Image) 4 weeks of placebo or TUDCA treatment. A: Hepatic insulin sensitivity index. B: Glucose rate of disappearance (Rd); data represent only 8 of 10 subjects who received TUDCA treatment because of technical difficulties in obtaining blood samples in two subjects. C: Palmitate rate of appearance. Values are means ± SD. *Value significantly different from corresponding value before treatment, P < 0.05. †Main effect of insulin, P < 0.0001.

  • FIG. 2.
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    FIG. 2.

    Effect of placebo (□) or TUDCA (Embedded Image) treatment on skeletal muscle IRSTyr, AktSer473, and JNKThr183/Tyr185 levels. Values are means ± SD and expressed relative to values before treatment, which were set to one for each person. *Value significantly different from corresponding placebo value, P < 0.05.

  • FIG. 3.
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    FIG. 3.

    Endoplasmic reticulum stress markers before (□) and after (Embedded Image) placebo or TUDCA therapy. A: Gene expression (relative to 18S rRNA). B: Protein content (relative to actin). Values are medians and quartiles.

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    Subjects' characteristics, metabolic variables, and body composition

    PlaceboTUDCA
    BeforeAfterBeforeAfter
    n (male/female)10 (4/6)—10 (4/6)—
    Age (years)49 ± 14—47 ± 9—
    BMI (kg/m2)37 ± 538 ± 535 ± 335 ± 3
    Total body mass (kg)109 ± 18110 ± 17100 ± 12100 ± 12
    Fat mass (%)39 ± 739 ± 739 ± 839 ± 8
    Subcutaneous abdominal fat volume (cm3)5,087 ± 1,7494,999 ± 1,6724,803 ± 1,2024,716 ± 1,188
    Intra-abdominal fat volume (cm3)2,146 ± 7892,172 ± 7162,724 ± 8462,818 ± 924
    IHTG content (%)14.0 ± 10.713.7 ± 9.68.2 ± 5.59.3 ± 7.2
    HOMA-IR4.2 ± 1.84.3 ± 1.74.4 ± 2.73.8 ± 3.4
    Plasma concentrations
        Glucose (mg/dl)97 ± 997 ± 1096 ± 994 ± 5
        Insulin (μU/ml)18 ± 718 ± 719 ± 1216 ± 15
        FFAs (mmol/l)0.59 ± 0.130.63 ± 0.150.62 ± 0.150.62 ± 0.19
        Triglycerides (mg/dl)154 ± 52145 ± 77136 ± 67141 ± 66
        AST (IU/l)25.9 ± 10.327.9 ± 14.522.4 ± 5.922.5 ± 6.1
        ALT (IU/l)30.3 ± 24.735.6 ± 34.926.9 ± 9.624.6 ± 8.1
        CRP (mg/l)5.67 ± 5.695.00 ± 3.875.40 ± 4.114.43 ± 2.94
        IL-6 (pg/ml)2.60 ± 0.952.44 ± 0.862.32 ± 0.652.60 ± 1.17
        Total adiponectin (mg/l)6.7 ± 3.86.9 ± 4.68.3 ± 3.18.3 ± 3.1
        HMW adiponectin (mg/l)2.2 ± 2.62.2 ± 2.93.1 ± 1.93.4 ± 2.4
    • Data are means ± SD. ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; HMW, high molecular weight; IL, interleukin.

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Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women
Marleen Kars, Ling Yang, Margaret F. Gregor, B. Selma Mohammed, Terri A. Pietka, Brian N. Finck, Bruce W. Patterson, Jay D. Horton, Bettina Mittendorfer, Gökhan S. Hotamisligil, Samuel Klein
Diabetes Aug 2010, 59 (8) 1899-1905; DOI: 10.2337/db10-0308

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Tauroursodeoxycholic Acid May Improve Liver and Muscle but Not Adipose Tissue Insulin Sensitivity in Obese Men and Women
Marleen Kars, Ling Yang, Margaret F. Gregor, B. Selma Mohammed, Terri A. Pietka, Brian N. Finck, Bruce W. Patterson, Jay D. Horton, Bettina Mittendorfer, Gökhan S. Hotamisligil, Samuel Klein
Diabetes Aug 2010, 59 (8) 1899-1905; DOI: 10.2337/db10-0308
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