Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease - PubMed (original) (raw)

Clinical Trial

Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease

Ciaran E Fealy et al. J Appl Physiol (1985). 2012 Jul.

Abstract

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis-plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)-in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m(2), >5% intrahepatic lipid (IHL) assessed by (1)H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (Vo(2max)) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = -0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.

PubMed Disclaimer

Figures

Fig. 1.

Fig. 1.

Short-term aerobic exercise training increases insulin sensitivity (A) and reduces circulating cytokeratin 18 (CK18) fragments (B), alanine aminotransferase (ALT) (C), and circulating soluble Fas ligand (sFasL) (D). Data are presented as means ± SE. *P < 0.05. OGTT, oral glucose tolerance test; ISIOGTT, insulin sensitivity (Matsuda) index; AU, arbitrary units.

Fig. 2.

Fig. 2.

Association between exercise training-induced percent changes in circulating CK18 and ALT in obese individuals with nonalcoholic fatty liver disease (NAFLD) (r = 0.55, P = 0.05). Δ, change.

Fig. 3.

Fig. 3.

Association between exercise training-induced changes in basal fat oxidation (FOX) and changes in circulating sFasL (rho = −0.65, P < 0.05).

Similar articles

Cited by

References

    1. American Gastroenterological Association American Gastroenterological medical position statement: nonalcoholic fatty liver disease. Gastroenterology 123: 1702–1704, 2002 - PubMed
    1. Akazawa Y, Gores GJ. Death receptor-mediated liver injury. Semin Liver Dis 27: 327–338, 2007 - PubMed
    1. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 346: 1221–1231, 2002 - PubMed
    1. Borengasser SJ, Rector RS, Uptergrove GM, Morris EM, Perfield JW, 2nd, Booth FW, Fritsche KL, Ibdah JA, Thyfault JP. Exercise and omega-3 polyunsaturated fatty acid supplementation for the treatment of hepatic steatosis in hyperphagic OLETF rats. J Nutr Metab 2012: 268680, 2012 - PMC - PubMed
    1. Bourey RE, Kohrt WM, Kirwan JP, Staten MA, King DS, Holloszy JO. Relationship between glucose tolerance and glucose-stimulated insulin response in 65-year olds. J Gerontol 48: M122–M127, 1993 - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources