Top

Acta Diabetologica

Published in:

01-07-2018 | Review Article

The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Authors: Azam Rezaei Farimani, Mitra Hariri, Mohsen Azimi-Nezhad, Abasalt Borji, Sadegh Zarei, Elham Hooshmand

Published in: Acta Diabetologica | Issue 7/2018

Abstract

Aim

N-3 PUFAs can potentially influence levels of inflammatory and non-inflammatory adipokines. Given the contradictory effects of n-3 PUFAs on serum levels of adipokines in type 2 diabetes, we conducted a systematic review and meta-analysis study of randomized placebo-controlled clinical trials that examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in patients with type 2 diabetes.

Methods

The electronic databases, without regard to language restrictions including PubMed/Medline, Google Scholar, SCOPUS and ISI Web of Science until August 2017, were used to identify randomized controlled trials that assessed the effect of n-3 PUFAs on serum leptin and adiponectin concentrations in type 2 diabetes. Outcomes were extracted based on the mean ± SD as effect size at baseline and end of the intervention. Between-study heterogeneity was evaluated by the I² estimates and their 95% CIs. Funnel plot asymmetry was used to investigate the existence of publication bias. Stata software and Review Manager were used for statistical data analysis.

Results

Data from 10 eligible articles involved 494 subjects with type 2 diabetes mellitus (intervention groups = 254 and control groups = 240), with age between 44 and 70 years, treated with doses of 0.52–7.4 g/day n-3 PUFAs. Adiponectin concentration nonsignificantly increased by a MD = 0.17 µg/mL (95% CI − 0.11, 0.44). Also, leptin concentration nonsignificantly reduced by a MD = − 0.31 ng/mL (95% CI − 0.69, 0.07).

Conclusion

Plant and marine sources of n-3 PUFAs can modify serum leptin and adiponectin levels by increasing adiponectin and decreasing leptin levels in patients with type 2 diabetes. Due to some limitations in this study, further studies are needed to reach a definitive conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin in T2DM.

Power C, Pereira SMP, Law C, Ki M (2014) Obesity and risk factors for cardiovascular disease and type 2 diabetes: investigating the role of physical activity and sedentary behaviour in mid-life in the 1958 British cohort. Atherosclerosis 233:363–369CrossRefPubMed

Qin L, Knol MJ, Corpeleijn E, Stolk RP (2010) Does physical activity modify the risk of obesity for type 2 diabetes: a review of epidemiological data. Eur J Epidemiol 25:5–12CrossRefPubMed

Finkelstein EA, Khavjou OA, Thompson H et al (2012) Obesity and severe obesity forecasts through 2030. Am J Prev Med 42:563–570CrossRefPubMed

Kwon H, Pessin JE (2013) Adipokines mediate inflammation and insulin resistance. Front Endocrinol 4:71CrossRef

Khan M, Joseph F (2014) Adipose tissue and adipokines: the association with and application of adipokines in obesity. Scientifica. https://doi.org/10.1155/2014/328592 CrossRefPubMedPubMedCentral

Arner P (2005) Insulin resistance in type 2 diabetes-role of the adipokines. Curr Mol Med 5:333–339CrossRefPubMed

Das P, Bhattacharjee D, Bandyopadhyay SK, Bhattacharya G, Singh R (2013) Association of obesity and leptin with insulin resistance in type 2 diabetes mellitus in Indian population. Indian J Physiol Pharmacol 57(1):45–50PubMed

Nomura S, Shouzu A, Omoto S et al (2009) Effects of eicosapentaenoic acid on endothelial cell-derived microparticles, angiopoietins and adiponectin in patients with type 2 diabetes. J Atheroscler Thromb 16:83–90CrossRefPubMed

Kang YE, Kim JM, Joung KH et al (2016) The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS ONE 11:e0154003CrossRefPubMedPubMedCentral

10.

Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85CrossRefPubMedPubMedCentral

11.

Evert AB, Boucher JL, Cypress M et al (2014) Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care 37:S120–S143CrossRefPubMed

12.

Simopoulos AP (2002) Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 21:495–505CrossRefPubMed

13.

von Frankenberg AD, Silva FM, de Almeida JC et al (2014) Effect of dietary lipids on circulating adiponectin: a systematic review with meta-analysis of randomised controlled trials. Br J Nutr 112:1235–1250CrossRef

14.

Wu JH, Cahill LE, Mozaffarian D (2013) Effect of fish oil on circulating adiponectin: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 98:2451–2459CrossRefPubMedPubMedCentral

15.

Hariri M, Ghiasvand R, Shiranian A, Askari G, Iraj B, Salehi-Abargouei A (2015) Does omega-3 fatty acids supplementation affect circulating leptin levels? A systematic review and meta-analysis on randomized controlled clinical trials. Clin Endocrinol 82:221–228CrossRef

16.

Balfegó M, Canivell S, Hanzu FA et al (2016) Effects of sardine-enriched diet on metabolic control, inflammation and gut microbiota in drug-naïve patients with type 2 diabetes: a pilot randomized trial. Lipids Health Dis 15:78CrossRefPubMedPubMedCentral

17.

Gomes PM, Hollanda-Miranda WR, Beraldo RA et al (2015) Supplementation of α-linolenic acid improves serum adiponectin levels and insulin sensitivity in patients with type 2 diabetes. Nutrition 31:853–857CrossRefPubMed

18.

Hashemi S, Sarbolouki S, Djalali M et al (2014) Adiponectin and glycemic profiles in type 2 diabetes patients on eicosapentaenoic acid with or without vitamin E. Acta Endocrinol (1841–0987). https://doi.org/10.4183/aeb.2014.84 CrossRef

19.

Jacobo-Cejudo MG, Valdés-Ramos R, Guadarrama-López AL, Pardo-Morales R-V, Martínez-Carrillo BE, Harbige LS (2017) Effect of n-3 polyunsaturated fatty acid supplementation on metabolic and inflammatory biomarkers in type 2 diabetes mellitus patients. Nutrients 9:573CrossRefPubMedCentral

20.

Kabir M, Skurnik G, Naour N et al (2007) Treatment for 2 mo with n − 3 polyunsaturated fatty acids reduces adiposity and some atherogenic factors but does not improve insulin sensitivity in women with type 2 diabetes: a randomized controlled study. Am J Clin Nutr 86:1670–1679CrossRefPubMed

21.

Lee TC, Ivester P, Hester AG et al (2014) The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population. Lipids Health Dis 13:196CrossRefPubMedPubMedCentral

22.

Mansoori A, Sotoudeh G, Djalali M et al (2015) Docosahexaenoic acid-rich fish oil supplementation improves body composition without influence of the PPARγ Pro12Ala polymorphism in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial. J Nutrigenet Nutrigenomics 8:195–204CrossRefPubMed

23.

Mazaherioun M, Saedisomeolia A, Javanbakht MH, Koohdani F, Eshraghian MR, Djalali M (2017) Beneficial effects of n-3 polyunsaturated fatty acids on adiponectin levels and AdipoR gene expression in patients with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blind clinical trial. Arch Med Sci 13:716CrossRefPubMed

24.

Taylor CG, Noto AD, Stringer DM, Froese S, Malcolmson L (2010) Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type 2 diabetes. J Am Coll Nutr 29:72–80CrossRefPubMed

25.

Veleba J, Kopecky J, Janovska P et al (2015) Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism. Nutr Metab 12:52CrossRef

26.

Moher D, Liberati A, Tetzlaff J, Altman DG, Prisma Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097CrossRefPubMedPubMedCentral

27.

Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13CrossRefPubMedPubMedCentral

28.

Verhagen AP, de Vet HC, de Bie RA et al (1998) The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 51:1235–1241CrossRefPubMed

29.

Mostad IL, Bjerve KS, Basu S, Sutton P, Frayn KN, Grill V (2009) Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus. Metabolism 58:1753–1761CrossRefPubMed

30.

Stirban A, Nandrean S, Götting C, Stratmann B, Tschoepe D (2014) Effects of n-3 polyunsaturated fatty acids (PUFAs) on circulating adiponectin and leptin in subjects with type 2 diabetes mellitus. Horm Metab Res 46:490–492PubMed

31.

Müllner E, Plasser E, Brath H et al (2014) Impact of polyunsaturated vegetable oils on adiponectin levels, glycaemia and blood lipids in individuals with type 2 diabetes: a randomised, double-blind intervention study. J Hum Nutr Diet 27:468–478CrossRefPubMed

32.

Nomura S, Inami N, Shouzu A et al (2009) The effects of pitavastatin, eicosapentaenoic acid and combined therapy on platelet-derived microparticles and adiponectin in hyperlipidemic, diabetic patients. Platelets 20:16–22CrossRefPubMed

33.

Ghorbani M, Hassani A, Donyaie A, Ghadiri M (2017) Effect of 8-week combined exercises with Omega 3 and l-carnitine supplements on serum visfatin levels in type 2 diabetic women. J Endocrinol Metab Res Center 19:18–25

34.

Hajianfar H, Hosseinzadeh MJ, Bahonar A et al (2011) The effect of omega-3 on the serum visfatin concentration in patients with type II diabetes. J Res Med Sci 16:490PubMedPubMedCentral

35.

Poreba M, Mostowik M, Siniarski A et al (2017) Treatment with high-dose n-3 PUFAs has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol 16:50CrossRefPubMedPubMedCentral

36.

Gray B, Steyn F, Davies P, Vitetta L (2013) Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management. Eur J Clin Nutr 67:1234–1242CrossRefPubMed

37.

Raclot T, Groscolas R, Langin D, Ferre P (1997) Site-specific regulation of gene expression by n-3 polyunsaturated fatty acids in rat white adipose tissues. J Lipid Res 38:1963–1972PubMed

38.

Reseland JE, Haugen F, Hollung K et al (2001) Reduction of leptin gene expression by dietary polyunsaturated fatty acids. J Lipid Res 42:743–750PubMed

39.

Pérez-Matute P, Pérez-Echarri N, Martínez JA, Marti A, Moreno-Aliaga MJ (2007) Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α. Br J Nutr 97:389–398CrossRefPubMed

40.

Peyron-Caso E, Taverna M, Guerre-Millo M et al (2002) Dietary (n-3) polyunsaturated fatty acids up-regulate plasma leptin in insulin-resistant rats. J Nutr 132:2235–2240CrossRefPubMed

41.

Moreno-Aliaga MJ, Lorente-Cebrián S, Martínez JA (2010) Regulation of adipokine secretion by n-3 fatty acids. Proc Nutr Soc 69:324–332CrossRefPubMed

42.

Ramel A, Parra D, Martinéz JA, Kiely M, Thorsdottir I (2009) Effects of seafood consumption and weight loss on fasting leptin and ghrelin concentrations in overweight and obese European young adults. Eur J Nutr 48:107–114CrossRefPubMed

43.

Monk JM, Turk HF, Liddle DM et al (2014) n-3 polyunsaturated fatty acids and mechanisms to mitigate inflammatory paracrine signaling in obesity-associated breast cancer. Nutrients 6:4760–4793CrossRefPubMedPubMedCentral

44.

Banga A, Unal R, Tripathi P et al (2009) Adiponectin translation is increased by the PPARγ agonists pioglitazone and ω-3 fatty acids. Am J Phys-Endocrinol Metab 296:E480–E489CrossRef

45.

Sukumar P, Sedo A, Li J et al (2012) Constitutively active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin. Circ Res CIRCRESAHA 112:270751

46.

Rosicka M, Krsek M, Matoulek M et al (2003) Serum ghrelin levels in obese patients: the relationship to serum leptin levels and soluble leptin receptors levels. Physiol Res 52:61–66PubMed

47.

Flachs P, Mohamed-Ali V, Horakova O et al (2006) Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 49:394–397CrossRefPubMed

48.

Itoh M, Suganami T, Satoh N et al (2007) Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 27:1918–1925CrossRefPubMed

49.

Tomas E, Tsao T-S, Saha AK et al (2002) Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl–CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci 99:16309–16313CrossRefPubMedPubMedCentral

50.

Yamauchi T, Kamon J, Ito Y et al (2003) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423:762–769CrossRefPubMed

51.

Adamia N, Virsaladze D, Charkviani N, Skhirtladze M, Khutsishvili M (2007) Effect of metformin therapy on plasma adiponectin and leptin levels in obese and insulin resistant postmenopausal females with type 2 diabetes. Georgian Med News 145:52–55

52.

Sharma PK, Bhansali A, Sialy R, Malhotra S, Pandhi P (2006) Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus. Clin Endocrinol 65:722–728CrossRef

Title: The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials
Authors: Azam Rezaei Farimani
Mitra Hariri
Mohsen Azimi-Nezhad
Abasalt Borji
Sadegh Zarei
Elham Hooshmand
Publication date: 01-07-2018
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 7/2018
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-018-1110-6

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Abstract

Aim

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aim

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2018

Characterization of circulating leukocytes and correlation of leukocyte subsets with metabolic parameters 1 and 5 years after diabetes diagnosis

Higher admission fasting plasma glucose levels are associated with a poorer short-term neurologic outcome in acute ischemic stroke patients with good collateral circulation

The relationship between the thickness of glomerular basement membrane and renal outcomes in patients with diabetic nephropathy

Insulin-mimetic effects of short-term rapamycin in type 1 diabetic patients prior to islet transplantation

Reply to Letter to the Editor “The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial”

Effect of resveratrol in type 2 diabetes oxidative stress markers: a reassessment

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page