Abstract
Background
Obesity and liver steatosis are both currently attributed to inappropriate lifestyle and nutrition. Higher prevalence of human adenovirus Ad36 seropositivity (Ad36+) is reported only in obesity.
Aims
To investigate whether a lifestyle-nutritional intervention achieves different outcomes in NAFLD patients, i.e., if is blunted or enhanced according to Ad36 seropositivity status.
Methods
One-year nutritional intervention was planned and accomplished for 62 non-alcoholic fatty liver disease overweight–obese patients, studied by liver ultrasound, evaluating Bright Liver Score (BLS), by Homeostatic Model assessment of Insulin Resistance (HOMA), by body composition and Ad36+ assay. Lower salt/lower calories Mediterranean diet, physical activity increase, smoking withdrawal and lifestyle counseling, provided by a health psychologist, were given.
Results
Ad36 seropositive patients have baseline greater BMI with the same level of BLS. Different prevalence of post-interventional response, significantly greater among Ad36+ patients, is observed: greater decrease of obesity, assessed by BMI, greater reduction of insulin resistance, assessed by HOMA and higher prevalence of bright liver disappearance.
A BMI-adjusted multiple linear regression model explains significantly 23.8% (p < 0.04) of the variance; significant predictive variables are Ad36 seropositivity (p < 0.012) and fat mass loss (p < 0.011) accounting for the variance of the occurrence of bright liver disappearance.
Conclusions
Ad36 previous infection is significantly associated with enhanced weight loss, bright liver disappearance, and recovery of insulin sensitivity through the chosen tailored nutritional interventional treatment. Nonetheless, Ad36 seronegative NAFLD patients’ fatty liver pattern improves, at a lower extent, also without significant weight loss: an effect of dietary changes profile, Mediterranean diet, not only of lowered food caloric intake, is conceivably operating.
Similar content being viewed by others
References
Roden M. Mechanisms of disease: hepatic steatosis in type 2 diabetes—pathogenesis and clinical relevance. Nat Clin Pract Endocrinol Metab. 2006;2:335–348.
Petersen KF, Dufour S, Feng J, et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci USA. 2006;103:18273–18277.
Lewis JR, Mohanty SR. Nonalcoholic fatty liver disease: a review and update. Dig Dis Sci. 2010;55:560–578.
Kallwitz ER, Kumar M, Aggarwal R, et al. Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: the impact of triglycerides. Dig Dis Sci. 2008;53:1358–1363.
Yeh MM, Brunt EM. Pathology of nonalcoholic fatty liver disease. Am J Clin Pathol. 2007;128:837–847.
Lim YS, Kim WR. The global impact of hepatic fibrosis and end-stage liver disease. Clin Liver Dis. 2008;12:733–746. vii.
Ariz U, Mato JM, Lu SC, Martínez Chantar ML. Nonalcoholic steatohepatitis, animal models, and biomarkers: what is new? Methods Mol Biol. 2010;593:109–136.
Malhi H, Gores GJ. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis. 2008;28:360–369.
Yu AS, Keeffe EB. NAFLD and NASH: important diseases before and after liver transplantation. Hepatology. 2001;34:842–843.
Gambarin-Gelwan M, Kinkhabwala SV, Schiano TD, Bodian C, Yeh HC, Futterweit W. Prevalence of nonalcoholic fatty liver disease in women with polycystic ovary syndrome. Clin Gastroenterol Hepatol. 2007;5:496–501.
Uslan I, Acarturk G, Karaca E, et al. The effects of weight loss on normal transaminase levels in obese patients. Am J Med Sci. 2007;334:327–330.
Verna EC, Berk PD. Role of fatty acids in the pathogenesis of obesity and fatty liver: impact of bariatric surgery. Semin Liver Dis. 2008;28:407–426.
Catalano D, Trovato GM, Martines GF, Randazzo M, Tonzuso A. Bright liver, body composition and insulin resistance changes with nutritional intervention: a follow-up study. Liver Int. 2008;28:1280–1287.
Larson-Meyer DE, Newcomer BR, Heilbronn LK, et al. Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity (Silver Spring). 2008;16:1355–1362.
Kirwan JP, Solomon TP, Wojta DM, Staten MA, Holloszy JO. Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab. 2009;297:E151–E156.
St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology. 2009;50:68–76.
Johnson NA, Sachinwalla T, Walton DW, et al. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology. 2009;50:1105–1112.
Kantartzis K, Thamer C, Peter A, et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut. 2009;58:1281–1288.
Riquelme A, Arrese M, Soza A, et al. Non-alcoholic fatty liver disease and its association with obesity, insulin resistance and increased serum levels of C-reactive protein in Hispanics. Liver Int. 2009;29:82–88.
Haukeland JW, Konopski Z, Eggesbø HB, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44:853–860.
Chalasani NP, Sanyal AJ, Kowdley KV, et al. Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design. Contemp Clin Trials. 2009;30:88–96.
Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395.
Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults–the evidence report. National Institutes of Health. Obes Res. 1998;6:51S–209S.
Allison DB, Downey M, Atkinson RL, et al. Obesity as a disease: a white paper on evidence and arguments commissioned by the Council of the Obesity Society. Obesity (Silver Spring). 2008;16:1161–1177.
Abdelmalek MF, Liu C, Shuster J, Nelson DR, Asal NR. Familial aggregation of insulin resistance in first-degree relatives of patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2006;4:1162–1169.
Tan HH, Fiel MI, Sun Q, et al. Kupffer cell activation by ambient air particulate matter exposure may exacerbate non-alcoholic fatty liver disease. J Immunotoxicol. 2009;6:266–275.
Younossi ZM, Baranova A, Ziegler K, et al. A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease. Hepatology. 2005;42:665–674.
Bell LN, Theodorakis JL, Vuppalanchi R, et al. Serum proteomics and biomarker discovery across the spectrum of nonalcoholic fatty liver disease. Hepatology. 2009;51:111–120.
Puri P, Wiest MM, Cheung O, et al. The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology. 2009;50:1827–1838.
Li L, Thompson LH, Zhao L, Messina JL. Tissue-specific difference in the molecular mechanisms for the development of acute insulin resistance after injury. Endocrinology. 2009;150:24–32.
Lyons MJ, Faust IM, Hemmes RB, Buskirk DR, Hirsch J, Zabriskie JB. A virally induced obesity syndrome in mice. Science. 1982;216:82–85.
Atkinson RL. Could viruses contribute to the worldwide epidemic of obesity? Int J Pediatr Obes. 2008;3:37–43.
Greenway F. Virus-induced obesity. Am J Physiol Regul Integr Comp Physiol. 2006;290:R188–R189.
Atkinson RL, Dhurandhar NV, Allison DB, et al. Human adenovirus-36 is associated with increased body weight and paradoxical reduction of serum lipids. Int J Obes (Lond). 2005;29:281–286.
Whigham LD, Israel BA, Atkinson RL. Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals. Am J Physiol Regul Integr Comp Physiol. 2006;290:R190–R194.
Trovato GM, Castro A, Tonzuso A, et al. Human obesity relationship with Ad36 adenovirus and insulin resistance. Int J Obes (Lond). 2009;33:1402–1409.
Na HN, Hong YM, Kim J, Kim HK, Jo I, Nam JH. Association between human adenovirus-36 and lipid disorders in Korean schoolchildren. Int J Obes (Lond). 2010;34:89–93.
Atkinson RL, Lee I, Shin HJ, He J. Human adenovirus-36 antibody status is associated with obesity in children. Int J Pediatr Obes. 2010;5:157–160.
Gabbert C, Donohue M, Arnold J, Schwimmer JB. Adenovirus 36 and obesity in children and adolescents. Pediatrics. 2010;126:721–726.
McLaughlin T, Schweitzer P, Carter S, et al. Persistence of improvement in insulin sensitivity following a dietary weight loss programme. Diabetes Obes Metab. 2008;10:1186–1194.
Pasarica M, Shin AC, Yu M, et al. Human adenovirus 36 induces adiposity, increases insulin sensitivity, and alters hypothalamic monoamines in rats. Obesity. 2006;14:1905–1913.
Rogers PM, Mashtalir N, Rathod MA, et al. Metabolically favorable remodeling of human adipose tissue by human adenovirus type 36. Diabetes. 2008;57:2321–2331.
Trovato GM, Martines GF, Garozzo A, et al. Ad36 adipogenic adenovirus in human non-alcoholic fatty liver disease. Liver Int. 2010;30:184–190.
Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348:2599–2608.
Mathiesen UL, Franzén LE, Aselius H, et al. Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases. Dig Liver Dis. 2002;34:516–522.
Ratziu V, Charlotte F, Heurtier A, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–1906.
Saadeh S, Younossi ZM, Remer EM, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–750.
Wang ZQ, Cefalu WT, Zhang XH, et al. Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling. Diabetes. 2008;57:1805–1813.
Rathod M, Vangipuram SD, Krishnan B, Heydari AR, Holland TC, Dhurandhar NV. Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes. Int J Obes (Lond). 2007;31:78–86.
Vangipuram SD, Yu M, Tian J, et al. Adipogenic human adenovirus-36 reduces leptin expression and secretion and increases glucose uptake by fat cells. Int J Obes (Lond). 2007;31:87–96.
Pasarica M, Mashtalir N, McAllister EJ, et al. Adipogenic human adenovirus Ad-36 induces commitment, differentiation, and lipid accumulation in human adipose-derived stem cells. Stem Cells. 2008;26:969–978.
Rathod MA, Rogers PM, Vangipuram SD, McAllister EJ, Dhurandhar NV. Adipogenic cascade can be induced without adipogenic media by a human adenovirus. Obesity (Silver Spring). 2009;17:657–664.
Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49:1877–1887.
Coyne CB, Bergelson JM. CAR: a virus receptor within the tight junction. Adv Drug Deliv Rev. 2005;57:869–882.
Guttman JA, Finlay BB. Tight junctions as targets of infectious agents. Biochim Biophys Acta. 2009;1788:832–841.
Gonzalez-Mariscal L, Garay E, Lechuga S. Virus interaction with the apical junctional complex. Front Biosci. 2009;14:731–768.
Rothenberg M, Cheung R, Ahmed A. Adenovirus-induced acute liver failure. Dig Dis Sci. 2009;54:218–221.
Atkinson AL. Human adenovirus-36 and non-alcoholic fatty liver disease. Liver Int. 2010;30:161–162.
Lambert E, Straznicky N, Eikelis N, et al. Gender differences in sympathetic nervous activity: influence of body mass and blood pressure. J Hypertens. 2007;25:1411–1419.
Sartorio A, Maffiuletti NA, Agosti F, Lafortuna CL. Gender-related changes in body composition, muscle strength and power output after a short-term multidisciplinary weight loss intervention in morbid obesity. J Endocrinol Invest. 2005;28:494–501.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Trovato, G.M., Martines, G.F., Trovato, F.M. et al. Adenovirus-36 Seropositivity Enhances Effects of Nutritional Intervention on Obesity, Bright Liver, and Insulin Resistance. Dig Dis Sci 57, 535–544 (2012). https://doi.org/10.1007/s10620-011-1903-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-011-1903-8