Expression enhancement in brown adipose tissue of genes related to thermogenesis and mitochondrial dynamics after administration of pepsin egg white hydrolysate.

Nutritional compounds could be a safe and less expensive treatment for complications associated with obesity and metabolic syndrome (MetS). The aim of this study was to investigate the mechanism of action and the target tissues of a pepsin egg white hydrolysate (EWH) which had previously been demonstrated to improve some obesity-related disorders on a high-fat/high-glucose rat model. Wistar rats were used and divided into 3 groups: Control group (C), High-fat/high-glucose diet (MS) and high-fat/high-glucose diet + EWH (MSH). The rats were fed for 20 weeks and the EWH was administered from the 9th week. At the end of the study, white adipose tissue (WAT), brown adipose tissue (BAT) and muscle samples were collected for RT-qPCR analyses and immunohistochemistry. Our results showed a gene expression enhancement (2-fold basal level) in BAT of genes related to thermogenesis and mitochondrial dynamics. Mitochondrial DNA quantification and immunohistochemistry results also showed an increase of the mitochondrial content in this tissue. In conclusion, our results show the potential metabolic effect of this pepsin EWH by enhancing mitochondrial proliferation and gene expression related to thermogenesis in BAT. The EWH could be used as a functional food ingredient which is able to increase energy expenditure and counteract obesity-related MetS in a chronically obese society.

[1]  R. López-Fandiño,et al.  Pepsin Egg White Hydrolysate Improves Glucose Metabolism Complications Related to Metabolic Syndrome in Zucker Fatty Rats , 2018, Nutrients.

[2]  C. Sale,et al.  Exercise-induced ‘browning’ of adipose tissues , 2018, Metabolism: clinical and experimental.

[3]  M. Miguel,et al.  Pepsin egg white hydrolysate ameliorates metabolic syndrome in high-fat/high-dextrose fed rats. , 2018, Food & function.

[4]  A. Rescifina,et al.  Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. A comprehensive systematic review. , 2017, European journal of medicinal chemistry.

[5]  S. Madhu,et al.  Development of metabolic syndrome in high-sucrose diet fed rats is not associated with decrease in adiponectin levels , 2017, Endocrine.

[6]  J. Landrier,et al.  Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response, and associated metabolic disorders. , 2017, Molecular nutrition & food research.

[7]  D. Clegg,et al.  Non‐shivering thermogenesis as a mechanism to facilitate sustainable weight loss , 2017, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[8]  A. Cicero,et al.  Potential role of bioactive peptides in prevention and treatment of chronic diseases: a narrative review , 2017, British journal of pharmacology.

[9]  C. Schéele,et al.  Metabolic regulation and the anti-obesity perspectives of human brown fat , 2017, Redox biology.

[10]  P. Trayhurn.  Origins and early development of the concept that brown adipose tissue thermogenesis is linked to energy balance and obesity. , 2017, Biochimie.

[11]  A. Palou,et al.  A nutritional perspective on UCP1-dependent thermogenesis. , 2017, Biochimie.

[12]  U. Förstermann,et al.  Restoration of perivascular adipose tissue function in diet‐induced obese mice without changing bodyweight , 2017, British journal of pharmacology.

[13]  Ping Li,et al.  Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet* , 2017, The Journal of Biological Chemistry.

[14]  A. Engin.  Adipose Tissue Hypoxia in Obesity and Its Impact on Preadipocytes and Macrophages: Hypoxia Hypothesis. , 2017, Advances in experimental medicine and biology.

[15]  G. Flores-Mateo,et al.  Metabolic syndrome and dietary patterns: a systematic review and meta-analysis of observational studies , 2017, European Journal of Nutrition.

[16]  A. Ramírez de Molina,et al.  Dietary Strategies Implicated in the Prevention and Treatment of Metabolic Syndrome , 2016, International journal of molecular sciences.

[17]  J. P. Castro,et al.  The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction , 2016, Biological chemistry.

[18]  J. Wada,et al.  Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes. , 2016, Acta medica Okayama.

[19]  S. Grundy.  Overnutrition, ectopic lipid and the metabolic syndrome , 2016, Journal of Investigative Medicine.

[20]  Christian M. Metallo,et al.  Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism , 2016, Nature Communications.

[21]  R. López-Fandiño,et al.  Pepsin Egg White Hydrolysate Ameliorates Obesity-Related Oxidative Stress, Inflammation and Steatosis in Zucker Fatty Rats , 2016, PloS one.

[22]  M. Jensen,et al.  Differential effects of leptin on adiponectin expression with weight gain versus obesity , 2015, International Journal of Obesity.

[23]  R. Rühl,et al.  Dietary regulation of adiponectin by direct and indirect lipid activators of nuclear hormone receptors. , 2016, Molecular nutrition & food research.

[24]  X. Huang,et al.  Resistin’s, obesity and insulin resistance: the continuing disconnect between rodents and humans , 2016, Journal of Endocrinological Investigation.

[25]  Xin Wang,et al.  Redox modulation of adipocyte differentiation: hypothesis of "Redox Chain" and novel insights into intervention of adipogenesis and obesity. , 2015, Free radical biology & medicine.

[26]  J. Ruiz,et al.  Role of Exercise in the Activation of Brown Adipose Tissue , 2015, Annals of Nutrition and Metabolism.

[27]  M. Fasshauer,et al.  Adipokines in health and disease. , 2015, Trends in pharmacological sciences.

[28]  A. Palou,et al.  All-trans retinoic acid induces oxidative phosphorylation and mitochondria biogenesis in adipocytes[S] , 2015, Journal of Lipid Research.

[29]  I. López-Expósito,et al.  Egg white hydrolysates with in vitro biological multiactivities to control complications associated with the metabolic syndrome , 2015, European Food Research and Technology.

[30]  M. Amiot,et al.  Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation. , 2014, The Journal of nutritional biochemistry.

[31]  J. Granneman,et al.  Adipose tissue plasticity from WAT to BAT and in between. , 2014, Biochimica et biophysica acta.

[32]  P. Seale,et al.  Brown and beige fat: development, function and therapeutic potential , 2013, Nature Medicine.

[33]  A. Dulloo.  The search for compounds that stimulate thermogenesis in obesity management: from pharmaceuticals to functional food ingredients , 2011, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[34]  R. López-Fandiño,et al.  Effect of the long-term intake of an egg white hydrolysate on the oxidative status and blood lipid profile of spontaneously hypertensive rats. , 2008, Food chemistry.

[35]  R. López-Fandiño,et al.  Vascular effects, angiotensin I-converting enzyme (ACE)-inhibitory activity, and antihypertensive properties of peptides derived from egg white. , 2007, Journal of agricultural and food chemistry.

[36]  R. López-Fandiño,et al.  Vasodilator effects of peptides derived from egg white proteins , 2007, Regulatory Peptides.

[37]  R. López-Fandiño,et al.  Long-term intake of egg white hydrolysate attenuates the development of hypertension in spontaneously hypertensive rats. , 2006, Life sciences.

[38]  R. López-Fandiño,et al.  Short-term effect of egg-white hydrolysate products on the arterial blood pressure of hypertensive rats , 2005, British Journal of Nutrition.

[39]  A. Dávalos,et al.  Antioxidant activity of peptides derived from egg white proteins by enzymatic hydrolysis. , 2004, Journal of food protection.

[40]  R. López-Fandiño,et al.  Angiotensin I-converting enzyme inhibitory activity of peptides derived from egg white proteins by enzymatic hydrolysis. , 2004, Journal of food protection.

[41]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[42]  K. Wirtz,et al.  The Peroxisome in Oxidative Stress , 2001, IUBMB life.

[43]  A. Stewart,et al.  Inducible nitric oxide synthase (iNOS) activity promotes ischaemic skin flap survival , 2001, British journal of pharmacology.