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01.01.2016 | Meta-Analysis

Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis

verfasst von: Stergios A. Polyzos, Konstantinos N. Aronis, Jannis Kountouras, Dimitrios D. Raptis, Maria F. Vasiloglou, Christos S. Mantzoros

Erschienen in: Diabetologia | Ausgabe 1/2016

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Abstract

Aims/hypothesis

Clinical data regarding circulating leptin levels in patients with non-alcoholic fatty liver disease (NAFLD) are conflicting. The purpose of this meta-analysis was to compare leptin levels between the following groups: patients with biopsy-proven NAFLD vs controls; simple steatosis (SS) patients vs controls; non-alcoholic steatohepatitis (NASH) patients vs controls and NASH patients vs SS patients.

Methods

We performed a systematic search in PubMed, Scopus and the Cochrane Library. We analysed 33 studies, published between 1999 and 2014, including 2,612 individuals (775 controls and 1,837 NAFLD patients).

Results

Higher circulating leptin levels were observed in NAFLD patients vs controls (standardised mean difference [SMD] 0.640; 95% CI 0.422, 0.858), SS patients vs controls (SMD 0.358; 95% CI 0.043, 0.673), NASH patients vs controls (SMD 0.617; 95% CI 0.403, 0.832) and NASH patients vs SS patients (SMD 0.209; 95% CI 0.023, 0.395). These results remained essentially unchanged after excluding studies involving paediatric or adolescent populations and/or individuals undergoing bariatric surgery. There was moderate-to-severe heterogeneity among studies in all comparisons, but no significant publication bias was detected. Meta-regression analysis demonstrated that BMI was inversely associated with leptin SMD and accounted for 26.5% (p = 0.014) and 32.7% (p = 0.021) of the between-study variance in the comparison between NASH patients and controls and NAFLD patients and controls, respectively. However, when bariatric studies were excluded, BMI did not significantly explain the between-study variance.

Conclusions/interpretation

Circulating leptin levels were higher in patients with NAFLD than in controls. Higher levels of circulating leptin were associated with increased severity of NAFLD, and the association remained significant after the exclusion of studies involving paediatric or adolescent populations and morbidly obese individuals subjected to bariatric surgery.

Nur mit Berechtigung zugänglich

Polyzos SA, Kountouras J, Zavos C (2009) Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 72:299–314CrossRef

Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34:274–285CrossRefPubMed

Kelesidis T, Kelesidis I, Chou S, Mantzoros CS (2010) Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 152:93–100PubMedCentralCrossRefPubMed

Moon HS, Dalamaga M, Kim SY et al (2013) Leptin’s role in lipodystrophic and nonlipodystrophic insulin-resistant and diabetic individuals. Endocr Rev 34:377–412PubMedCentralCrossRefPubMed

Mantzoros CS, Magkos F, Brinkoetter M et al (2011) Leptin in human physiology and pathophysiology. Am J Physiol Endocrinol Metab 301:E567–E584PubMedCentralCrossRefPubMed

Dalamaga M, Chou SH, Shields K, Papageorgiou P, Polyzos SA, Mantzoros CS (2013) Leptin at the intersection of neuroendocrinology and metabolism: current evidence and therapeutic perspectives. Cell Metab 18:29–42CrossRefPubMed

Polyzos SA, Kountouras J, Zavos C, Deretzi G (2011) The potential adverse role of leptin resistance in nonalcoholic fatty liver disease: a hypothesis based on critical review of literature. J Clin Gastroenterol 45:50–54CrossRefPubMed

Imajo K, Fujita K, Yoneda M et al (2012) Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab 16:44–54CrossRefPubMed

Polyzos SA, Kountouras J, Mantzoros CS (2015) Leptin in nonalcoholic fatty liver disease: a narrative review. Metabolism 64:60–78CrossRefPubMed

10.

Polyzos SA, Mantzoros CS (2014) Necessity for timely noninvasive diagnosis of nonalcoholic fatty liver disease. Metabolism 63:161–167CrossRefPubMed

11.

Polyzos SA, Mantzoros CS (2015) Leptin in health and disease: facts and expectations at its twentieth anniversary. Metabolism 64:5–12CrossRefPubMed

12.

Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRefPubMed

13.

Polyzos SA, Toulis KA, Goulis DG, Zavos C, Kountouras J (2011) Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism 60:313–326CrossRefPubMed

14.

Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94:2467–2474CrossRefPubMed

15.

Kleiner DE, Brunt EM, Van NM et al (2005) Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41:1313–1321CrossRefPubMed

16.

Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269CrossRefPubMed

17.

Angulo P, Alba LM, Petrovic LM, Adams LA, Lindor KD, Jensen MD (2004) Leptin, insulin resistance, and liver fibrosis in human nonalcoholic fatty liver disease. J Hepatol 41:943–949CrossRefPubMed

18.

Argentou M, Tiniakos DG, Karanikolas M et al (2009) Adipokine serum levels are related to liver histology in severely obese patients undergoing bariatric surgery. Obes Surg 19:1313–1323CrossRefPubMed

19.

Canbakan B, Tahan V, Balci H et al (2008) Leptin in nonalcoholic fatty liver disease. Ann Hepatol 7:249–254PubMed

20.

Cayon A, Crespo J, Mayorga M, Guerra A, Pons-Romero F (2006) Increased expression of Ob-Rb and its relationship with the overexpression of TGF-β1 and the stage of fibrosis in patients with nonalcoholic steatohepatitis. Liver Int 26:1065–1071CrossRefPubMed

21.

Chalasani N, Crabb DW, Cummings OW et al (2003) Does leptin play a role in the pathogenesis of human nonalcoholic steatohepatitis? Am J Gastroenterol 98:2771–2776CrossRefPubMed

22.

Charlton M, Angulo P, Chalasani N et al (2008) Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology 47:484–492PubMedCentralCrossRefPubMed

23.

Chitturi S, Farrell G, Frost L et al (2002) Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? Hepatology 36:403–409CrossRefPubMed

24.

Dasarathy S, Yang Y, McCullough AJ, Marczewski S, Bennett C, Kalhan SC (2011) Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis. Eur J Gastroenterol Hepatol 23:382–388PubMedCentralCrossRefPubMed

25.

Fitzpatrick E, Dew TK, Quaglia A, Sherwood RA, Mitry RR, Dhawan A (2012) Analysis of adipokine concentrations in paediatric non-alcoholic fatty liver disease. Pediatr Obes 7:471–479CrossRefPubMed

26.

Giannini E, Botta F, Cataldi A et al (1999) Leptin levels in nonalcoholic steatohepatitis and chronic hepatitis C. Hepatogastroenterology 46:2422–2425PubMed

27.

Gonciarz M, Bielanski W, Partyka R et al (2013) Plasma insulin, leptin, adiponectin, resistin, ghrelin, and melatonin in nonalcoholic steatohepatitis patients treated with melatonin. J Pineal Res 54:154–161CrossRefPubMed

28.

Haukeland JW, Dahl TB, Yndestad A et al (2012) Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies. Eur J Endocrinol 166:503–510CrossRefPubMed

29.

Huang XD, Fan Y, Zhang H et al (2008) Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease. World J Gastroenterol 14:2888–2893PubMedCentralCrossRefPubMed

30.

Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J (2004) Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 40:46–54CrossRefPubMed

31.

Kashyap SR, Diab DL, Baker AR et al (2009) Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring) 17:1696–1701CrossRef

32.

Koehler E, Swain J, Sanderson S, Krishnan A, Watt K, Charlton M (2012) Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients. Liver Int 32:279–286CrossRefPubMed

33.

Le D, Marks D, Lyle E et al (2007) Serum leptin levels, hepatic leptin receptor transcription, and clinical predictors of non-alcoholic steatohepatitis in obese bariatric surgery patients. Surg Endosc 21:1593–1599CrossRefPubMed

34.

Lemoine M, Ratziu V, Kim M et al (2009) Serum adipokine levels predictive of liver injury in non-alcoholic fatty liver disease. Liver Int 29:1431–1438CrossRefPubMed

35.

Machado MV, Coutinho J, Carepa F, Costa A, Proenca H, Cortez-Pinto H (2012) How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 24:1166–1172CrossRefPubMed

36.

Manco M, Giordano U, Turchetta A et al (2009) Insulin resistance and exercise capacity in male children and adolescents with non-alcoholic fatty liver disease. Acta Diabetol 46:97–104CrossRefPubMed

37.

Munoz LE, Cordero P, Torres L, Sauceda AY, Flores JP, Segura JJ (2009) Adipokines in a group of Mexican patients with nonalcoholic steatohepatitis. Ann Hepatol 8:123–128PubMed

38.

Musso G, Gambino R, Durazzo M et al (2005) Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology 42:1175–1183CrossRefPubMed

39.

Nobili V, Manco M, Ciampalini P et al (2006) Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease. Eur J Endocrinol 155:735–743CrossRefPubMed

40.

Pagano C, Soardo G, Esposito W et al (2005) Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol 152:113–118CrossRefPubMed

41.

Petta S, Amato MC, Di Marco V et al (2012) Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 35:238–247CrossRefPubMed

42.

Pirvulescu I, Gheorghe L, Csiki I et al (2012) Noninvasive clinical model for the diagnosis of nonalcoholic steatohepatitis in overweight and morbidly obese patients undergoing bariatric surgery. Chirurgia (Bucur) 107:772–779

43.

Polyzos SA, Kountouras J, Anastasilakis AD, Geladari EV, Mantzoros CS (2014) Irisin in patients with nonalcoholic fatty liver disease. Metabolism 63:207–217CrossRefPubMed

44.

Singh DK, Sakhuja P, Rastogi A, Singh A, Gondal R, Sarin SK (2013) Serum leptin levels correlate with body mass index but not with histologic disease severity in Indian patients with non-alcoholic steatohepatitis: a pilot study. Indian J Med Res 137:986–987PubMedCentralPubMed

45.

Swellam M, Hamdy N (2012) Association of nonalcoholic fatty liver disease with a single nucleotide polymorphism on the gene encoding leptin receptor. IUBMB Life 64:180–186CrossRefPubMed

46.

Tungtrongchitr R, Treeprasertsuk S, Ei NN, Thepouyporn A, Phonrat B, Huntrup A (2006) Serum leptin concentrations in chronic hepatitis. J Med Assoc Thail 89:490–499

47.

Uygun A, Kadayifci A, Yesilova Z et al (2000) Serum leptin levels in patients with nonalcoholic steatohepatitis. Am J Gastroenterol 95:3584–3589CrossRefPubMed

48.

Wong VW, Hui AY, Tsang SW et al (2006) Metabolic and adipokine profile of Chinese patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 4:1154–1161CrossRefPubMed

49.

Yalniz M, Bahcecioglu IH, Ataseven H et al (2006) Serum adipokine and ghrelin levels in nonalcoholic steatohepatitis. Mediat Inflamm 2006:34295CrossRef

50.

Egger M, Juni P, Bartlett C, Holenstein F, Sterne J (2003) How important are comprehensive literature searches and the assessment of trial quality in systematic reviews? Empirical study. Health Technol Assess 7:1–76PubMed

Titel: Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis
verfasst von: Stergios A. Polyzos
Konstantinos N. Aronis
Jannis Kountouras
Dimitrios D. Raptis
Maria F. Vasiloglou
Christos S. Mantzoros
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 1/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-015-3769-3

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Circulating leptin in non-alcoholic fatty liver disease: a systematic review and meta-analysis

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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