Effects of plant and animal high protein diets on immune-inflammatory biomarkers: A 6-week intervention trial

  • Author Footnotes
    1 The authors contributed equally to the manuscript writing.
    Mariya Markova
    Correspondence
    Corresponding author. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Fax: +49 33200 88 2777.
    Footnotes
    1 The authors contributed equally to the manuscript writing.
    Affiliations
    Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Germany
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  • Author Footnotes
    1 The authors contributed equally to the manuscript writing.
    Liselot Koelman
    Footnotes
    1 The authors contributed equally to the manuscript writing.
    Affiliations
    Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
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  • Silke Hornemann
    Affiliations
    Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Germany
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  • Olga Pivovarova
    Affiliations
    Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Germany

    Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
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  • Stephanie Sucher
    Affiliations
    Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Germany
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  • Juergen Machann
    Affiliations
    University of Tübingen, Experimental Radiology, Tübingen, Germany
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  • Natalia Rudovich
    Affiliations
    Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Germany

    Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany

    Division of Endocrinology and Diabetology, Clinic of Internal Medicine, Hospital of Buelach, Buelach, Switzerland
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  • Ralph Thomann
    Affiliations
    Institut für Getreideverarbeitung GmbH, Nuthetal, Germany
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  • Rosemarie Schneeweiss
    Affiliations
    Institute for Food and Environmental Research, Nuthetal, Germany
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  • Sascha Rohn
    Affiliations
    Institute for Food and Environmental Research, Nuthetal, Germany

    Institute of Food Chemistry, Hamburg School of Food Science, University of Hamburg, Hamburg, Germany
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  • Andreas F.H. Pfeiffer
    Affiliations
    Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    German Center for Diabetes Research (DZD), Germany

    Department of Endocrinology, Diabetes and Nutrition, Campus Benjamin Franklin, Charité University Medicine, Berlin, Germany
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  • Krasimira Aleksandrova
    Correspondence
    Corresponding author. Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. Fax: +49 33200 88 2721.
    Affiliations
    Senior Scientist Group Nutrition, Immunity and Metabolism, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

    University of Potsdam, Institute of Nutritional Science, Potsdam, Germany
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  • Author Footnotes
    1 The authors contributed equally to the manuscript writing.
Published:March 27, 2019DOI:https://doi.org/10.1016/j.clnu.2019.03.019

      Summary

      Background & aims

      Pro-inflammatory biomarkers are well-established contributors to insulin resistance and represent valid targets for diabetes management and prevention. Yet, little is known whether nutrition could play a role in modulating various aspects of immune-inflammatory responses. Our aim is to assess the effect of isocaloric animal and plant protein dietary interventions on selected biomarkers representing various immune-inflammatory pathways.

      Methods

      We enrolled 37 participants with type 2 diabetes (age 64 ± 6 years, body mass index 30.2 ± 3.6 kg/m2, glycated hemoglobin 7.0 ± 0.6%) who underwent an either high-animal protein (AP) or high-plant protein (PP) diet (30 E% protein, 40 E% carbohydrates, 30 E% fat) for 6-weeks. Clinical examinations were performed at beginning and end of the study. Levels of pro-inflammatory adipokines [chemerin, progranulin], cytokines [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble urokinase-type plasminogen activator receptor (suPAR), transforming growth factor beta 1 (TGF-β1)], and proteins [calprotectin, lactoferrin and growth differentiation factor 15 (GDF-15)] were determined in blood serum using enzyme-linked immunosorbent assay.

      Results

      Chemerin and progranulin concentrations decreased following AP and PP diets. TGF-β1 increased in AP and decreased in PP, whereas calprotectin increased in PP and decreased in AP. No statistically significant differences in the concentrations of IL-6, TNF-α, suPAR, lactoferrin and GDF-15 could be seen in either of the protein diet arms.

      Conclusions

      These results suggest that both AP and PP diets may effectively reduce the levels of the pro-inflammatory adipokines chemerin and progranulin. The effects on the additional immune-inflammatory biomarkers seem to be more complex.

      Clinical trial registry number

      Keywords

      Abbreviations:

      AP (Animal protein), BMI (Body mass index), CID (Clinical investigation day), CRP (C-reactive protein), E% (Percent of total daily energy intake), ELISA (Enzyme-linked immunosorbent assay), GDF-15 (Growth differentiation factor 15), GGT (Gamma-glutamyltransferase), HbA1c (Glycated hemoglobin), HDL (High density lipoprotein), HP (High protein), IL (Interleukin), PP (Plant protein), SuPAR (Soluble urokinase-type plasminogen activator receptor), T2D (Type 2 diabetes), TGF-β1 (Transforming growth factor beta 1), TNF-α (Tumor necrosis factor alpha), WC (Waist circumference)
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      References

        • Cornell S.
        Continual evolution of type 2 diabetes: an update on pathophysiology and emerging treatment options.
        Therapeut Clin Risk Manag. 2015; 11: 621-632
        • Shu C.J.
        • Benoist C.
        • Mathis D.
        The immune system's involvement in obesity-driven type 2 diabetes.
        Semin Immunol. 2012; 24: 436-442
        • Samuel V.T.
        • Shulman G.I.
        Mechanisms for insulin resistance: common threads and missing links.
        Cell. 2012; 148: 852-871
        • Samuel V.T.
        • Shulman G.I.
        The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux.
        J Clin Investig. 2016; 126: 12-22
        • Lackey D.E.
        • Olefsky J.M.
        Regulation of metabolism by the innate immune system.
        Nat Rev Endocrinol. 2016; 12: 15-28
        • Sell H.
        • Habich C.
        • Eckel J.
        Adaptive immunity in obesity and insulin resistance.
        Nat Rev Endocrinol. 2012; 8: 709-716
        • Thomas D.
        • Apovian C.
        Macrophage functions in lean and obese adipose tissue.
        Metabolism. 2017; 72: 120-143
        • Larsen T.M.
        • Dalskov S.M.
        • van Baak M.
        • Jebb S.A.
        • Papadaki A.
        • Pfeiffer A.F.
        • et al.
        Diets with high or low protein content and glycemic index for weight-loss maintenance.
        N Engl J Med. 2010; 363: 2102-2113
        • Soenen S.
        • Bonomi A.G.
        • Lemmens S.G.
        • Scholte J.
        • Thijssen M.A.
        • van Berkum F.
        • et al.
        Relatively high-protein or 'low-carb' energy-restricted diets for body weight loss and body weight maintenance?.
        Physiol Behav. 2012; 107: 374-380
        • Nuttall F.Q.
        • Gannon M.C.
        Metabolic response of people with type 2 diabetes to a high protein diet.
        Nutr Metabol. 2004; 1: 6
        • Gannon M.C.
        • Nuttall F.Q.
        Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes.
        Diabetes. 2004; 53: 2375-2382
        • Sucher S.
        • Markova M.
        • Hornemann S.
        • Pivovarova O.
        • Rudovich N.
        • Thomann R.
        • et al.
        Comparison of the effects of diets high in animal or plant protein on metabolic and cardiovascular markers in type 2 diabetes: a randomized clinical trial.
        Diabetes Obes Metab. 2017; 19: 944-952
        • Kim K.O.
        • Park H.
        • Kim H.S.
        Effects of high-protein diet and/or resveratrol supplementation on the immune response of irradiated rats.
        Prev Nutr Food Sci. 2014; 19: 156-163
        • Burris R.L.
        • Ng H.P.
        • Nagarajan S.
        Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-kappaB and AKT signaling pathway in apolipoprotein E-deficient mice.
        Eur J Nutr. 2014; 53: 135-148
        • Sellmann C.
        • Jin C.J.
        • Degen C.
        • De Bandt J.P.
        • Bergheim I.
        Oral glutamine supplementation protects female mice from nonalcoholic steatohepatitis.
        J Nutr. 2015; 145: 2280-2286
        • Markova M.
        • Pivovarova O.
        • Hornemann S.
        • Sucher S.
        • Frahnow T.
        • Wegner K.
        • et al.
        Isocaloric diets high in animal or plant protein reduce liver fat and inflammation in individuals with type 2 diabetes.
        Gastroenterology. 2016; 152: 571-585 e8
        • Gogebakan O.
        • Kohl A.
        • Osterhoff M.A.
        • van Baak M.A.
        • Jebb S.A.
        • Papadaki A.
        • et al.
        Effects of weight loss and long-term weight maintenance with diets varying in protein and glycemic index on cardiovascular risk factors: the diet, obesity, and genes (DiOGenes) study: a randomized, controlled trial.
        Circulation. 2011; 124: 2829-2838
        • Pasiakos S.M.
        • Cao J.J.
        • Margolis L.M.
        • Sauter E.R.
        • Whigham L.D.
        • McClung J.P.
        • et al.
        Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial.
        FASEB J – Off Publ Fed Am Soc Exp Biol. 2013; 27: 3837-3847
        • Bauer J.
        • Biolo G.
        • Cederholm T.
        • Cesari M.
        • Cruz-Jentoft A.J.
        • Morley J.E.
        • et al.
        Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group.
        J Am Med Dir Assoc. 2013; 14: 542-559
        • Guadagni M.
        • Biolo G.
        Effects of inflammation and/or inactivity on the need for dietary protein.
        Curr Opin Clin Nutr Metab Care. 2009; 12: 617-622
        • Holmer-Jensen J.
        • Karhu T.
        • Mortensen L.S.
        • Pedersen S.B.
        • Herzig K.H.
        • Hermansen K.
        Differential effects of dietary protein sources on postprandial low-grade inflammation after a single high fat meal in obese non-diabetic subjects.
        Nutr J. 2011; 10: 115
        • Tomayko E.J.
        • Kistler B.M.
        • Fitschen P.J.
        • Wilund K.R.
        Intradialytic protein supplementation reduces inflammation and improves physical function in maintenance hemodialysis patients.
        J Ren Nutr. 2015; 25: 276-283
        • Lopez-Legarrea P.
        • de la Iglesia R.
        • Abete I.
        • Navas-Carretero S.
        • Martinez J.A.
        • Zulet M.A.
        The protein type within a hypocaloric diet affects obesity-related inflammation: the RESMENA project.
        Nutrition. 2014; 30: 424-429
        • Lachine N.A.
        • Elnekiedy A.A.
        • Megallaa M.H.
        • Khalil G.I.
        • Sadaka M.A.
        • Rohoma K.H.
        • et al.
        Serum chemerin and high-sensitivity C reactive protein as markers of subclinical atherosclerosis in Egyptian patients with type 2 diabetes.
        Ther Adv Endocrinol Metab. 2016; 7: 47-56
        • Habib S.S.
        • Eshki A.
        • AlTassan B.
        • Fatani D.
        • Helmi H.
        • AlSaif S.
        Relationship of serum novel adipokine chemerin levels with body composition, insulin resistance, dyslipidemia and diabesity in Saudi women.
        Eur Rev Med Pharmacol Sci. 2017; 21: 1296-1302
        • Du J.
        • Li R.
        • Xu L.
        • Ma R.
        • Liu J.
        • Cheng J.
        • et al.
        Increased serum chemerin levels in diabetic retinopathy of type 2 diabetic patients.
        Curr Eye Res. 2016; 41: 114-120
        • Weigert J.
        • Neumeier M.
        • Wanninger J.
        • Filarsky M.
        • Bauer S.
        • Wiest R.
        • et al.
        Systemic chemerin is related to inflammation rather than obesity in type 2 diabetes.
        Clin Endocrinol (Oxf). 2010; 72: 342-348
        • Xu L.
        • Zhou B.
        • Li H.X.
        • Liu J.L.
        • Du J.H.
        • Zang W.J.
        • et al.
        Serum levels of progranulin are closely associated with microvascular complication in type 2 diabetes.
        Dis Markers. 2015; : 1-9
        • Nicoletto B.B.
        • Pedrollo E.F.
        • Carpes L.S.
        • Coloretti N.G.
        • Krolikowski T.C.
        • Souza G.C.
        • et al.
        Progranulin serum levels in human kidney transplant recipients: a longitudinal study.
        PLoS One. 2018; 13e0192959
        • Al-Shukaili A.
        • AL-Ghafri S.
        • Al-Marhoobi S.
        • Al-Abri S.
        • Al-Lawati J.
        • Al-Maskari M.
        Analysis of inflammatory mediators in type 2 diabetes patients.
        Int J Endocrinol. 2013; 2013: 7
        • Darko S.N.
        • Yar D.D.
        • Owusu-Dabo E.
        • Awuah A.A.-A.
        • Dapaah W.
        • Addofoh N.
        • et al.
        Variations in levels of IL-6 and TNF-α in type 2 diabetes mellitus between rural and urban Ashanti Region of Ghana.
        BMC Endocr Disord. 2015; 15: 50
        • Hossain M.
        • Faruque M.O.
        • Kabir G.
        • Hassan N.
        • Sikdar D.
        • Nahar Q.
        • et al.
        Association of serum TNF-α and IL-6 with insulin secretion and insulin resistance in IFG and IGT subjects in a Bangladeshi population.
        Int J Diabetes Mellitus. 2010; 2: 165-168
        • Shikano M.
        • Sobajima H.
        • Yoshikawa H.
        • Toba T.
        • Kushimoto H.
        • Katsumata H.
        • et al.
        Usefulness of a highly sensitive urinary and serum IL-6 assay in patients with diabetic nephropathy.
        Nephron. 2000; 85: 81-85
        • Guthoff M.
        • Wagner R.
        • Randrianarisoa E.
        • Hatziagelaki E.
        • Peter A.
        • Häring H.-U.
        • et al.
        Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus.
        Sci Rep. 2017; 7: 40627
        • Aslan S.
        • Demirdal T.
        • Nemli A.
        • Erbak H.
        • Aslan C.
        • Vardar I.
        • et al.
        The diagnostic role of suPAR for diabetic foot infections.
        Open Forum Infec Dis. 2015; 2: 1523
        • Moreno-Navarrete J.M.
        • Ortega F.J.
        • Bassols J.
        • Ricart W.
        • Fernandez-Real J.M.
        Decreased circulating lactoferrin in insulin resistance and altered glucose tolerance as a possible marker of neutrophil dysfunction in type 2 diabetes.
        J Clin Endocrinol Metab. 2009; 94: 4036-4044
        • Hong J.H.
        • Chung H.K.
        • Park H.Y.
        • Joung K.H.
        • Lee J.H.
        • Jung J.G.
        • et al.
        GDF15 is a novel biomarker for impaired fasting glucose.
        Diabetes Metab J. 2014; 38: 472-479
        • Pavo N.
        • Wurm R.
        • Neuhold S.
        • Adlbrecht C.
        • Vila G.
        • Strunk G.
        • et al.
        GDF-15 is associated with cancer incidence in patients with type 2 diabetes.
        Clin Chem. 2016; 62: 1612-1620
        • Shin M.Y.
        • Kim J.M.
        • Kang Y.E.
        • Kim M.K.
        • Joung K.H.
        • Lee J.H.
        • et al.
        Association between growth differentiation factor 15 (GDF15) and cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus.
        J Korean Med Sci. 2016; 31: 1413-1418
        • Shaker Y.M.
        • Soliman H.A.
        • Ezzat E.
        • Hussein N.S.
        • Ashour E.
        • Donia A.
        • et al.
        Serum and urinary transforming growth factor beta 1 as biochemical markers in diabetic nephropathy patients.
        Beni-Suef Univ J Basic Appl Sci. 2014; 3: 16-23
        • Zorena K.
        • Malinowska E.
        • Raczynska D.
        • Mysliwiec M.
        • Raczynska K.
        Serum concentrations of transforming growth factor-Beta 1 in predicting the occurrence of diabetic retinopathy in juvenile patients with type 1 diabetes mellitus.
        J Diabetes Res. 2013; 2013: 614908
        • Schaan B.D.
        • Quadros A.S.
        • Sarmento-Leite R.
        • De Lucca Jr., G.
        • Bender A.
        • Bertoluci M.
        Correction:' Serum transforming growth factor beta-1 (TGF-beta-1) levels in diabetic patients are not associated with pre-existent coronary artery disease.
        Cardiovasc Diabetol. 2007; 6: 19
        • Roohi A.
        • Tabrizi M.
        • Abbasi F.
        • Ataie-Jafari A.
        • Nikbin B.
        • Larijani B.
        • et al.
        Serum IL-17, IL-23, and TGF-beta levels in type 1 and type 2 diabetic patients and age-matched healthy controls.
        BioMed Res Int. 2014; 2014: 718946
        • Szczepaniak L.S.
        • Nurenberg P.
        • Leonard D.
        • Browning J.D.
        • Reingold J.S.
        • Grundy S.
        • et al.
        Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population.
        Am J Physiol Endocrinol Metab. 2005; 288: E462-E468
        • Kitabchi A.E.
        • McDaniel K.A.
        • Wan J.Y.
        • Tylavsky F.A.
        • Jacovino C.A.
        • Sands C.W.
        • et al.
        Effects of high-protein versus high-carbohydrate diets on markers of beta-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial.
        Diabetes Care. 2013; 36: 1919-1925
        • Katsuki A.
        • Sumida Y.
        • Murashima S.
        • Murata K.
        • Takarada Y.
        • Ito K.
        • et al.
        Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus.
        J Clin Endocrinol Metab. 1998; 83: 859-862
        • Pei R.
        • DiMarco D.M.
        • Putt K.K.
        • Martin D.A.
        • Gu Q.
        • Chitchumroonchokchai C.
        • et al.
        Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial.
        Br J Nutr. 2017; 118: 1043-1051
        • Labonté M.-È.
        • Cyr A.
        • Abdullah M.M.
        • Lépine M.-C.
        • Vohl M.-C.
        • Jones P.
        • et al.
        Dairy product consumption has No impact on biomarkers of inflammation among men and women with low-grade systemic inflammation.
        J Nutr. 2014; 144: 1760-1767
        • Tavenier J.
        • Haupt T.H.
        • Andersen A.L.
        • Buhl S.F.
        • Langkilde A.
        • Andersen J.R.
        • et al.
        A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS.
        Nutr Res. 2017; 41: 56-64
        • Eichelmann F.
        • Schwingshackl L.
        • Fedirko V.
        • Aleksandrova K.
        Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials.
        Obes Rev. 2016; 17: 1067-1079
        • Pedersen A.N.
        • Kondrup J.
        • Borsheim E.
        Health effects of protein intake in healthy adults: a systematic literature review.
        Food Nutr Res. 2013; 57
        • Eichelmann F.
        • Weikert C.
        • di Giuseppe R.
        • Biemann R.
        • Isermann B.
        • Schulze M.B.
        • et al.
        Methodological utility of chemerin as a novel biomarker of immunity and metabolism.
        Endocr Connect. 2017; 6: 340-347
        • Pfeiffer A.
        • Middelberg-Bisping K.
        • Drewes C.
        • Schatz H.
        Elevated plasma levels of transforming growth factor-beta 1 in NIDDM.
        Diabetes Care. 1996; 19: 1113-1117
        • Ziyadeh F.N.
        Mediators of diabetic renal disease: the case for tgf-Beta as the major mediator.
        J Am Soc Nephrol – JASN. 2004; 15: S55-S57
        • Yan J.
        • Zhang H.
        • Yin Y.
        • Li J.
        • Tang Y.
        • Purkayastha S.
        • et al.
        Obesity- and aging-induced excess of central transforming growth factor-beta potentiates diabetic development via an RNA stress response.
        Nat Med. 2014; 20: 1001-1008
        • Wakefield A.P.
        • House J.D.
        • Ogborn M.R.
        • Weiler H.A.
        • Aukema H.M.
        A diet with 35% of energy from protein leads to kidney damage in female Sprague-Dawley rats.
        Br J Nutr. 2011; 106: 656-663
        • Tovar-Palacio C.
        • Tovar A.R.
        • Torres N.
        • Cruz C.
        • Hernandez-Pando R.
        • Salas-Garrido G.
        • et al.
        Proinflammatory gene expression and renal lipogenesis are modulated by dietary protein content in obese Zucker fa/fa rats.
        Am J Physiol Renal Physiol. 2011; 300: F263-F271
        • Yoshiji H.
        • Noguchi R.
        • Ikenaka Y.
        • Kaji K.
        • Aihara Y.
        • Douhara A.
        • et al.
        Combination of branched-chain amino acid and angiotensin-converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis.
        Mol Med Rep. 2012; 5: 539-544
        • Takegoshi K.
        • Honda M.
        • Okada H.
        • Takabatake R.
        • Matsuzawa-Nagata N.
        • Campbell J.S.
        • et al.
        Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model.
        Oncotarget. 2017; 8: 18191-18205
        • Cypers H.
        • Varkas G.
        • Beeckman S.
        • Debusschere K.
        • Vogl T.
        • Roth J.
        • et al.
        Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis.
        Ann Rheum Dis. 2015; 75: 1357-1362
        • Hang I.
        • Heilmann R.M.
        • Grützner N.
        • Suchodolski J.S.
        • Steiner J.M.
        • Atroshi F.
        • et al.
        Impact of diets with a high content of greaves-meal protein or carbohydrates on faecal characteristics, volatile fatty acids and faecal calprotectin concentrations in healthy dogs.
        BMC Vet Res. 2013; 9: 201
        • Ohlsson B.
        • Roth B.
        • Larsson E.
        • Hoglund P.
        Calprotectin in serum and zonulin in serum and feces are elevated after introduction of a diet with lower carbohydrate content and higher fiber, fat and protein contents.
        Biomed Rep. 2017; 6: 411-422
        • Yang D.
        • Elner S.G.
        • Bian Z.M.
        • Till G.O.
        • Petty H.R.
        • Elner V.A.
        Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells.
        Exp Eye Res. 2007; 85: 462-472
        • Eichelmann F.
        • Rudovich N.
        • Pfeiffer A.F.
        • Schulze M.B.
        • Giuseppe R.D.
        • Boeing H.
        • et al.
        Novel adipokines: methodological utility in human obesity research.
        Int J Obes (Lond). 2017; 41: 976-981