Whey Peptides Stimulate Differentiation and Lipid Metabolism in Adipocytes and Ameliorate Lipotoxicity-Induced Insulin Resistance in Muscle Cells
"> Figure 1
<p>Effect of whey peptides on 3T3-L1 adipocyte differentiation. 3T3-L1 preadipocytes were differentiated in the presence of 2.5 mg/mL WPI, WPH, BPI or BPH. Immunoblotting and densitometric analysis of (<b>A</b>,<b>B)</b> PPARγ, (<b>A</b>,<b>C</b>) C/EBPα, and (<b>A</b>,<b>D</b>) adiponectin (<span class="html-italic">n</span> = 6). mRNA levels of PPARγ (<b>E</b>) and PPARγ target genes, (<b>F</b>) adiponectin and (<b>G</b>) stearoyl-CoA desaturase (Scd1) (<span class="html-italic">n</span> = 8) were determined. TG levels (<b>H</b>) were measured using a targeted lipidomics approach in adipocytes incubated with BSA protein isolate or whey peptides (<span class="html-italic">n</span> = 8). (<b>B</b>–<b>H</b>): * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001 vs. protein isolate controls. BPI, BSA protein isolate; BPH, BSA peptide hydrolysate; WPI, whey protein isolate; WPH, whey peptide hydrolysate; PPARγ, peroxisome proliferator-activated receptor γ; C/EBPα, CCAAT/enhancer-binding protein α; PS, protein stain; Scd1, stearoyl-Coenzyme A desaturase 1; A.U., arbitrary units.</p> "> Figure 2
<p>Influence of whey peptides on lipolysis in 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated in presence of 2.5 mg/mL WPI, WPH, BPI, or BPH. (<b>A</b>) <span class="html-italic">PPARδ</span> mRNA levels were determined (<span class="html-italic">n</span> = 8). Immunoblotting and densitometric analysis were performed to assess protein levels of (<b>B</b>,<b>C</b>) pHSL<sup>S660</sup>, (<b>B</b>,<b>D</b>) HSL, (<b>B</b>,<b>E</b>) ATGL, and (<b>B</b>,<b>F</b>) perilipin-1 (<span class="html-italic">n</span> = 6). (<b>G</b>) Basal and isoproterenol-stimulated lipolysis and (<b>H</b>,<b>I</b>) insulin-mediated suppression of lipolysis was determined in adipocytes incubated with BSA protein isolate or whey peptides (<span class="html-italic">n</span> = 6). <b>A</b>, <b>C</b>–<b>I</b>: * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001 vs. protein isolate controls or as indicated. <sup>#</sup> <span class="html-italic">p</span> < 0.05, <sup>####</sup> <span class="html-italic">p</span> < 0.0001 in peptide vs. protein-treated adipocytes. HSL, hormone-sensitive lipase; ATGL, adipose triglyceride lipase; PS, protein stain; NEFA, non-esterified fatty acids; A.U., arbitrary units.</p> "> Figure 3
<p>Effect of whey peptides on mitochondrial function in adipocytes. 3T3-L1 preadipocytes were differentiated in the presence of 2.5 mg/mL WPI, WPH, BPI, or BPH. (<b>A</b>) <span class="html-italic">Pgc1α</span> mRNA levels and (<b>B</b>) citrate synthase activity (<span class="html-italic">n</span> = 7–8). (<b>C</b>) Fatty acid-linked mitochondrial respiration and (<b>D</b>) uncoupled respiration was assessed in permeabilized adipocytes incubated with BSA protein isolate or whey peptides (<span class="html-italic">n</span> = 7). (<b>A</b>–<b>D</b>): **** <span class="html-italic">p</span> < 0.0001 vs. protein controls or as indicated. <sup>####</sup> <span class="html-italic">p</span> < 0.0001 for peptide vs. protein-treated adipocytes. Pgc1α, PPARγ coactivator 1-α; Pc, palmitoylcarnitine; M, malate; D, ADP.</p> "> Figure 4
<p>Effect of whey peptides on insulin signaling in C2C12 myotubes. C2C12 myotubes were incubated in the presence or absence of 0.4 mM palmitate and co-incubated with 2.5 mg/mL BPI, BPH, WPI, or WPH. Immunoblotting and densiometric analysis were performed to assess (<b>A</b>,<b>B</b>) AKT phosphorylation at S473 and (<b>C</b>,<b>D</b>) Glut4 protein levels (<span class="html-italic">n</span> = 6). (<b>B</b>,<b>D</b>): *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001 as indicated. <sup>#</sup> <span class="html-italic">p</span> < 0.05, <sup>###</sup> <span class="html-italic">p</span> < 0.001 for peptide vs. protein treated myotubes. A.U., arbitrary units.</p> "> Figure 5
<p>Influence of whey peptides on palmitate-induced ER stress, inflammation, and DG accumulation in C2C12 myotubes. C2C12 myotubes were incubated in the presence or absence of 0.4 mM palmitate and co-incubated with 2.5 mg/mL BPI, BPH, WPI or WPH. Immunoblotting and densiometric analysis were performed to assess (<b>A</b>,<b>B</b>) protein levels of CHOP and (<b>A</b>,<b>C</b>) phosphorylation JNK at T183/Y185 (<span class="html-italic">n</span> = 6). mRNA levels of inflammatory markers, (<b>D</b>) <span class="html-italic">Mcp1</span> and (<b>E</b>) <span class="html-italic">Tnfα</span> (<span class="html-italic">n</span> = 8) were determined. Levels of (<b>F</b>) DGs were measured using a targeted lipidomic approach (<span class="html-italic">n</span> = 6–8). (<b>B</b>–<b>E</b>): * <span class="html-italic">p</span> < 0.05, ** <span class="html-italic">p</span> < 0.01, *** <span class="html-italic">p</span> < 0.001, **** <span class="html-italic">p</span> < 0.0001 vs. no palmitate controls or as indicated. <sup>#</sup> <span class="html-italic">p</span> < 0.05, <sup>###</sup> <span class="html-italic">p</span> < 0.001, <sup>####</sup> <span class="html-italic">p</span> < 0.0001 as indicated. CHOP, C/EBP homologous protein; JNK, c-Jun N-terminal kinase; <span class="html-italic">Mcp1</span>, monocyte chemoattractant protein 1; <span class="html-italic">Tnfα</span>, tumor necrosis factor α; Palm, palmitate; A.U., arbitrary units.</p> "> Figure 6
<p>Effect of whey peptides on fatty acid transporter levels, TG accumulation, and mitochondrial abundance. C2C12 myotubes were incubated in the presence or absence of 0.4 mM palmitate and co-incubated with 2.5 mg/mL BPI, BPH, WPI, or WPH. (<b>A</b>) mRNA levels of <span class="html-italic">Fatp1</span> (<span class="html-italic">n</span> = 8) were assessed. (<b>B</b>) TG levels were measured using a targeted lipidomics approach (<span class="html-italic">n</span> = 8). (<b>C</b>) <span class="html-italic">Pgc1α</span> mRNA levels (<span class="html-italic">n</span> = 8), (<b>D</b>) citrate synthase activity (<span class="html-italic">n</span> = 3), and (<b>E</b>) uncoupled respiration (<span class="html-italic">n</span> = 7) were determined in myotubes treated with BSA protein isolate or whey peptides. ** <span class="html-italic">p</span> < 0.01, **** <span class="html-italic">p</span> < 0.0001 vs. no palmitate controls or as indicated, <sup>####</sup> <span class="html-italic">p</span> < 0.0001 as indicated. <span class="html-italic">Fatp1</span>, fatty acid transport protein 1; <span class="html-italic">Pgc1α</span>, peroxisome proliferator-activated receptor γ coactivator 1-α; A.U., arbitrary units.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals and Reagents
2.2. Preparation of Protein and Peptide Mixtures
2.3. Cell Culture
2.4. Gene Expression Analysis
2.5. Immunoblotting Analysis
2.6. Lipid Analysis
2.7. Lipolysis Assay
2.8. Mitochondrial Analysis
2.9. Citrate Synthase Activity Assay
2.10. Statistical Analysis
3. Results
3.1. Profile of Peptides in Whey Protein Hydrolysate
3.2. Whey Peptides Promote Differentiation of 3T3-L1 Adipocytes
3.3. Whey Peptides Increase Lipolysis in 3T3-L1 Adipocytes
3.4. Whey Peptides Enhance Mitochondrial Fatty Acid Oxidation in 3T3-L1 Adipocytes
3.5. Whey Peptides Ameliorate Palmitate-Induced Insulin Resistance in C2C12 Myotubes
3.6. Whey Peptides Protect from Palmitate-Induced Inflammation and Endoplasmic Reticulum (ER) Stress, Which is Associated with Decreased DG Accumulation in C2C12 Myotubes
3.7. Whey Peptides Increase TG Accumulation in C2C12 Myotubes
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- DeFronzo, R.A.; Tripathy, D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009, 32 (Suppl. 2), S157–S163. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baron, A.D.; Brechtel, G.; Wallace, P.; Edelman, S.V. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am. J. Physiol. 1988, 255 (6 Pt 1), E769–E774. [Google Scholar] [CrossRef] [PubMed]
- Rutkowski, J.M.; Stern, J.H.; Scherer, P.E. The cell biology of fat expansion. J. Cell. Biol. 2015, 208, 501–512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Griffin, M.E.; Marcucci, M.J.; Cline, G.W.; Bell, K.; Barucci, N.; Lee, D.; Goodyear, L.J.; Kraegen, E.W.; White, M.F.; Shulman, G.I. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 1999, 48, 1270–1274. [Google Scholar] [CrossRef]
- Kim, J.Y.; van de Wall, E.; Laplante, M.; Azzara, A.; Trujillo, M.E.; Hofmann, S.M.; Schraw, T.; Durand, J.L.; Li, H.; Li, G.; et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. J. Clin. Invest. 2007, 117, 2621–2637. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ouchi, N.; Parker, J.L.; Lugus, J.J.; Walsh, K. Adipokines in inflammation and metabolic disease. Nat. Rev. Immunol. 2011, 11, 85–97. [Google Scholar] [CrossRef]
- Scheja, L.; Heeren, J. The endocrine function of adipose tissues in health and cardiometabolic disease. Nat. Rev. Endocrinol. 2019, 15, 507–524. [Google Scholar] [CrossRef]
- Freitas Lima, L.C.; Braga, V.A.; do Socorro de Franca Silva, M.; Cruz, J.C.; Sousa Santos, S.H.; de Oliveira Monteiro, M.M.; Balarini, C.M. Adipokines, diabetes and atherosclerosis: An inflammatory association. Front. Physiol. 2015, 6, 304. [Google Scholar] [CrossRef]
- Makki, K.; Froguel, P.; Wolowczuk, I. Adipose tissue in obesity-related inflammation and insulin resistance: Cells, cytokines, and chemokines. ISRN Inflamm. 2013, 2013, 139239. [Google Scholar] [CrossRef] [Green Version]
- Wu, H.; Ballantyne, C.M. Skeletal muscle inflammation and insulin resistance in obesity. J. Clin. Invest. 2017, 127, 43–54. [Google Scholar] [CrossRef]
- Anderson, E.J.; Lustig, M.E.; Boyle, K.E.; Woodlief, T.L.; Kane, D.A.; Lin, C.T.; Price, J.W., 3rd; Kang, L.; Rabinovitch, P.S.; Szeto, H.H.; et al. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J. Clin. Invest. 2009, 119, 573–581. [Google Scholar] [CrossRef] [PubMed]
- Kang, L.; Ayala, J.E.; Lee-Young, R.S.; Zhang, Z.; James, F.D.; Neufer, P.D.; Pozzi, A.; Zutter, M.M.; Wasserman, D.H. Diet-induced muscle insulin resistance is associated with extracellular matrix remodeling and interaction with integrin alpha2beta1 in mice. Diabetes 2011, 60, 416–426. [Google Scholar] [CrossRef] [Green Version]
- Koh, H.J.; Toyoda, T.; Didesch, M.M.; Lee, M.Y.; Sleeman, M.W.; Kulkarni, R.N.; Musi, N.; Hirshman, M.F.; Goodyear, L.J. Tribbles 3 mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. Nat. Commun. 2013, 4, 1871. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adams, J.M., 2nd; Pratipanawatr, T.; Berria, R.; Wang, E.; DeFronzo, R.A.; Sullards, M.C.; Mandarino, L.J. Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes 2004, 53, 25–31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Szendroedi, J.; Yoshimura, T.; Phielix, E.; Koliaki, C.; Marcucci, M.; Zhang, D.; Jelenik, T.; Muller, J.; Herder, C.; Nowotny, P.; et al. Role of diacylglycerol activation of PKCtheta in lipid-induced muscle insulin resistance in humans. Proc. Natl. Acad. Sci. USA 2014, 111, 9597–9602. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Udenigwe, C.C.; Rouvinen-Watt, K. The Role of Food Peptides in Lipid Metabolism during Dyslipidemia and Associated Health Conditions. Int. J. Mol. Sci. 2015, 16, 9303–9313. [Google Scholar] [CrossRef] [Green Version]
- Udenigwe, C.C.; Aluko, R.E. Food protein-derived bioactive peptides: Production, processing, and potential health benefits. J. Food. Sci. 2012, 77, R11–R24. [Google Scholar] [CrossRef]
- Chakrabarti, S.; Wu, J. Milk-derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) promote adipocyte differentiation and inhibit inflammation in 3T3-F442A cells. PLoS ONE 2015, 10, e0117492. [Google Scholar] [CrossRef] [Green Version]
- Sawada, Y.; Sakamoto, Y.; Toh, M.; Ohara, N.; Hatanaka, Y.; Naka, A.; Kishimoto, Y.; Kondo, K.; Iida, K. Milk-derived peptide Val-Pro-Pro (VPP) inhibits obesity-induced adipose inflammation via an angiotensin-converting enzyme (ACE) dependent cascade. Mol. Nutr. Food. Res. 2015, 59, 2502–2510. [Google Scholar] [CrossRef]
- Jahandideh, F.; Chakrabarti, S.; Davidge, S.T.; Wu, J. Egg white hydrolysate shows insulin mimetic and sensitizing effects in 3T3-F442A preadipocytes. PLoS ONE 2017, 12, e0185653. [Google Scholar] [CrossRef] [Green Version]
- Li, S.; Liu, L.; He, G.; Wu, J. Molecular targets and mechanisms of bioactive peptides against metabolic syndromes. Food. Funct. 2018, 9, 42–52. [Google Scholar] [CrossRef] [PubMed]
- De Campos Zani, S.C.; Wu, J.; Chan, C.B. Egg and Soy-Derived Peptides and Hydrolysates: A Review of Their Physiological Actions against Diabetes and Obesity. Nutrients 2018, 10, 549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ewert, J.; Luz, A.; Volk, V.; Stressler, T.; Fischer, L. Enzymatic production of emulsifying whey protein hydrolysates without the need of heat inactivation. J. Sci. Food. Agric. 2019, 99, 3443–3450. [Google Scholar] [CrossRef]
- Ichinoseki-Sekine, N.; Kakigi, R.; Miura, S.; Naito, H. Whey peptide ingestion suppresses body fat accumulation in senescence-accelerated mouse prone 6 (SAMP6). Eur. J. Nutr. 2015, 54, 551–556. [Google Scholar] [CrossRef] [PubMed]
- Gao, J.; Song, J.; Du, M.; Mao, X. Bovine alpha-Lactalbumin Hydrolysates (alpha-LAH) Ameliorate Adipose Insulin Resistance and Inflammation in High-Fat Diet-Fed C57BL/6J Mice. Nutrients 2018, 10, 242. [Google Scholar] [CrossRef] [Green Version]
- Mohammed-Geba, K.; Arrutia, F.; Do-Huu, H.; Borrell, Y.J.; Galal-Khallaf, A.; Ardura, A.; Riera, F.A.; Garcia-Vazquez, E. VY6, a beta-lactoglobulin-derived peptide, altered metabolic lipid pathways in the zebra fish liver. Food. Funct. 2016, 7, 1968–1974. [Google Scholar] [CrossRef] [Green Version]
- Morifuji, M.; Sakai, K.; Sanbongi, C.; Sugiura, K. Dietary whey protein increases liver and skeletal muscle glycogen levels in exercise-trained rats. Br. J. Nutr. 2005, 93, 439–445. [Google Scholar] [CrossRef] [Green Version]
- Kanda, A.; Morifuji, M.; Fukasawa, T.; Koga, J.; Kanegae, M.; Kawanaka, K.; Higuchi, M. Dietary whey protein hydrolysates increase skeletal muscle glycogen levels via activation of glycogen synthase in mice. J. Agric. Food. Chem. 2012, 60, 11403–11408. [Google Scholar] [CrossRef]
- Morifuji, M.; Koga, J.; Kawanaka, K.; Higuchi, M. Branched-chain amino acid-containing dipeptides, identified from whey protein hydrolysates, stimulate glucose uptake rate in L6 myotubes and isolated skeletal muscles. J. Nutr. Sci. Vitaminol. 2009, 55, 81–86. [Google Scholar] [CrossRef] [Green Version]
- Tyanova, S.; Temu, T.; Cox, J. The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nat. Protoc. 2016, 11, 2301–2319. [Google Scholar] [CrossRef]
- D’Souza, K.; Kane, D.A.; Touaibia, M.; Kershaw, E.E.; Pulinilkunnil, T.; Kienesberger, P.C. Autotaxin is Regulated by Glucose and Insulin in Adipocytes. Endocrinology 2017, 158, 791–803. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Souza, K.; Nzirorera, C.; Cowie, A.M.; Varghese, G.P.; Trivedi, P.; Eichmann, T.O.; Biswas, D.; Touaibia, M.; Morris, A.J.; Aidinis, V.; et al. Autotaxin-Lysophosphatidic Acid Signaling Contributes to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism. J. Lipid. Res. 2018, 59, 1805–1817. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Perez, L.J.; Rios, L.; Trivedi, P.; D’Souza, K.; Cowie, A.; Nzirorera, C.; Webster, D.; Brunt, K.; Legare, J.F.; Hassan, A.; et al. Validation of optimal reference genes for quantitative real time PCR in muscle and adipose tissue for obesity and diabetes research. Sci. Rep. 2017, 7, 3612. [Google Scholar] [CrossRef] [PubMed]
- Matyash, V.; Liebisch, G.; Kurzchalia, T.V.; Shevchenko, A.; Schwudke, D. Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J. Lipid. Res. 2008, 49, 1137–1146. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Breitkopf, S.B.; Ricoult, S.J.H.; Yuan, M.; Xu, Y.; Peake, D.A.; Manning, B.D.; Asara, J.M. A relative quantitative positive/negative ion switching method for untargeted lipidomics via high resolution LC-MS/MS from any biological source. Metabolomics 2017, 13, 30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boudina, S.; Sena, S.; O’Neill, B.T.; Tathireddy, P.; Young, M.E.; Abel, E.D. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 2005, 112, 2686–2695. [Google Scholar] [CrossRef] [Green Version]
- Agyei, D.; Tsopmo, A.; Udenigwe, C.C. Bioinformatics and peptidomics approaches to the discovery and analysis of food-derived bioactive peptides. Anal. Bioanal. Chem. 2018, 410, 3463–3472. [Google Scholar] [CrossRef]
- Larsen, S.; Nielsen, J.; Hansen, C.N.; Nielsen, L.B.; Wibrand, F.; Stride, N.; Schroder, H.D.; Boushel, R.; Helge, J.W.; Dela, F.; et al. Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects. J. Physiol. 2012, 590, 3349–3360. [Google Scholar] [CrossRef]
- Sadeghi, A.; Seyyed Ebrahimi, S.S.; Golestani, A.; Meshkani, R. Resveratrol Ameliorates Palmitate-Induced Inflammation in Skeletal Muscle Cells by Attenuating Oxidative Stress and JNK/NF-kappaB Pathway in a SIRT1-Independent Mechanism. J. Cell. Biochem. 2017, 118, 2654–2663. [Google Scholar] [CrossRef]
- Perry, B.D.; Rahnert, J.A.; Xie, Y.; Zheng, B.; Woodworth-Hobbs, M.E.; Price, S.R. Palmitate-induced ER stress and inhibition of protein synthesis in cultured myotubes does not require Toll-like receptor 4. PLoS ONE 2018, 13, e0191313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Samuel, V.T.; Shulman, G.I. Mechanisms for insulin resistance: Common threads and missing links. Cell 2012, 148, 852–871. [Google Scholar] [CrossRef] [Green Version]
- Xu, S.P.; Mao, X.Y.; Ren, F.Z.; Che, H.L. Attenuating effect of casein glycomacropeptide on proliferation, differentiation, and lipid accumulation of in vitro Sprague-Dawley rat preadipocytes. J. Dairy. Sci. 2011, 94, 676–683. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, Y.M.; Kim, I.H.; Choi, J.W.; Lee, M.K.; Nam, T.J. The anti-obesity effects of a tuna peptide on 3T3-L1 adipocytes are mediated by the inhibition of the expression of lipogenic and adipogenic genes and by the activation of the Wnt/beta-catenin signaling pathway. Int. J. Mol. Med. 2015, 36, 327–334. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.X. PPARs: Diverse regulators in energy metabolism and metabolic diseases. Cell. Res. 2010, 20, 124–137. [Google Scholar] [CrossRef]
- Roberts, L.D.; Murray, A.J.; Menassa, D.; Ashmore, T.; Nicholls, A.W.; Griffin, J.L. The contrasting roles of PPARdelta and PPARgamma in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue. Genome. Biol. 2011, 12, R75. [Google Scholar] [CrossRef] [Green Version]
- Matsusue, K.; Peters, J.M.; Gonzalez, F.J. PPARbeta/delta potentiates PPARgamma-stimulated adipocyte differentiation. FASEB J. 2004, 18, 1477–1479. [Google Scholar] [CrossRef] [PubMed]
- Cox, R.L. Rationally designed PPARdelta-specific agonists and their therapeutic potential for metabolic syndrome. Proc. Natl. Acad. Sci. USA 2017, 114, 3284–3285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baer, D.J.; Stote, K.S.; Paul, D.R.; Harris, G.K.; Rumpler, W.V.; Clevidence, B.A. Whey protein but not soy protein supplementation alters body weight and composition in free-living overweight and obese adults. J. Nutr. 2011, 141, 1489–1494. [Google Scholar] [CrossRef]
- Lopes Gomes, D.; Moehlecke, M.; Lopes da Silva, F.B.; Dutra, E.S.; D’Agord Schaan, B.; Baiocchi de Carvalho, K.M. Whey Protein Supplementation Enhances Body Fat and Weight Loss in Women Long After Bariatric Surgery: A Randomized Controlled Trial. Obes. Surg. 2017, 27, 424–431. [Google Scholar] [CrossRef]
- Tranberg, B.; Hellgren, L.I.; Lykkesfeldt, J.; Sejrsen, K.; Jeamet, A.; Rune, I.; Ellekilde, M.; Nielsen, D.S.; Hansen, A.K. Whey protein reduces early life weight gain in mice fed a high-fat diet. PLoS ONE 2013, 8, e71439. [Google Scholar] [CrossRef] [Green Version]
- Lu, J.; Zeng, Y.; Hou, W.; Zhang, S.; Li, L.; Luo, X.; Xi, W.; Chen, Z.; Xiang, M. The soybean peptide aglycin regulates glucose homeostasis in type 2 diabetic mice via IR/IRS1 pathway. J. Nutr. Biochem. 2012, 23, 1449–1457. [Google Scholar] [CrossRef] [PubMed]
- Soga, M.; Ohashi, A.; Taniguchi, M.; Matsui, T.; Tsuda, T. The di-peptide Trp-His activates AMP-activated protein kinase and enhances glucose uptake independently of insulin in L6 myotubes. FEBS Open. Bio. 2014, 4, 898–904. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kwak, S.J.; Kim, C.S.; Choi, M.S.; Park, T.; Sung, M.K.; Yun, J.W.; Yoo, H.; Mine, Y.; Yu, R. The Soy Peptide Phe-Leu-Val Reduces TNFalpha-Induced Inflammatory Response and Insulin Resistance in Adipocytes. J. Med. Food. 2016, 19, 678–685. [Google Scholar] [CrossRef] [PubMed]
- Petersen, M.C.; Shulman, G.I. Mechanisms of Insulin Action and Insulin Resistance. Physiol. Rev. 2018, 98, 2133–2223. [Google Scholar] [CrossRef] [Green Version]
- Listenberger, L.L.; Han, X.; Lewis, S.E.; Cases, S.; Farese, R.V., Jr.; Ory, D.S.; Schaffer, J.E. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc. Natl. Acad. Sci. USA 2003, 100, 3077–3082. [Google Scholar] [CrossRef] [Green Version]
- Sitnick, M.T.; Basantani, M.K.; Cai, L.; Schoiswohl, G.; Yazbeck, C.F.; Distefano, G.; Ritov, V.; Delany, J.P.; Schreiber, R.; Stolz, D.B.; et al. Skeletal muscle triacylglycerol hydrolysis does not influence metabolic complications of obesity. Diabetes 2013, 62, 3350–3361. [Google Scholar] [CrossRef] [Green Version]
- Goodpaster, B.H.; He, J.; Watkins, S.; Kelley, D.E. Skeletal muscle lipid content and insulin resistance: Evidence for a paradox in endurance-trained athletes. J. Clin. Endocrinol. Metab. 2001, 86, 5755–5761. [Google Scholar] [CrossRef]
Target | Primer Sequence (5’ to 3’) |
---|---|
Pparγ F | ACATAAAGTCCTTCCCGCTGA |
Pparγ R | TCGAAACTGGCACCCTTGAAAA |
Adipoq F | AGCCGCTTATGTGTATCGC |
Adipoq R | GTCCCGGAATGTTGCAGTAGAAC |
Scd1 F | TTACGACCGGAAGAAAGTT |
Scd1 R | ATTAACACCCCGATAGCAATA |
Pparδ F | TCATTGAGCCCAAGTTCGAGT |
Pparδ R | CCGGTCTCCACACAAAATGAT |
Pgc1α F | TTTGCCCAGATCTTCCTGAAC |
Pgc1α R | TCGCTACACCACTTCAATCCA |
Mcp1 F | TCGGAACCAAATGAGATCAGA |
Mcp1 R | CAGATTTACGGGTCAACTTC |
Tnfα F | CATCCATTCTCTACCCAGCCC |
Tnfα R | CATGAGAGGCCCACAGTCCA |
Fatp1 F | CCTCTGGGCACCATTCTATATTC |
Fatp1 R | ACACTAGCCACATCCAAGTGA |
Rpl27 F | ACGGTGGAGCCTTATGTGAC |
Rpl27 R | TCCGTCAGAGGGACTGTCTT |
Rpl41 F | GCCATGAGAGCGAAGTGG |
Rpl41 R | CTCCTGCAGGCGTCGTAG |
Rpl7 F | ACGGTGGAGCCTTATGTGAC |
Rpl7 R | TCCGTCAGAGGGACTGTCTT |
Rer1 F | GCCTTGGGAATTTACCACCT |
Rer1 R | CTTCGAATGAAGGGACGAAA |
ID | Whey Protein Groups Identified | Major Protein UniProtKB Accession Number | Number of Peptides Identified | % of Total Number of Peptides |
---|---|---|---|---|
1 | Alpha-lactalbumin | P00711 | 69 | 26.2 |
2 | Alpha-S2-casein | P02663 | 1 | 0.4 |
3 | Beta-casein | P02666 | 21 | 8.0 |
4 | Kappa-casein | P02668 | 17 | 6.5 |
5 | Serum albumin (BSA) | P02769 | 16 | 6.1 |
6 | Osteopontin | P31096 | 1 | 0.4 |
7 | Serotransferrin | Q29443 | 2 | 0.8 |
8 | Ig-like domain-containing protein | F1MLW7 | 2 | 0.8 |
9 | Alpha-amylase | Q3MHH8 | 2 | 0.8 |
10 | Folate receptor alpha | P02702 | 2 | 0.8 |
11 | Beta-lactoglobulin | P02754 | 115 | 43.7 |
12 | Lactotransferrin | P24627 | 2 | 0.8 |
13 | NPC intracellular cholesterol transporter 2 | P79345 | 4 | 1.5 |
14 | Glycosylation-dependent cell adhesion molecule 1 | P80195 | 2 | 0.8 |
15 | Lactadherin | G3MYW7 | 1 | 0.4 |
16 | Sortilin related VPS10 domain containing receptor 1 | A0A3Q1LSH9 | 1 | 0.4 |
17 | Multiple coagulation factor deficiency 2 | Q3MHJ4 | 1 | 0.4 |
18 | Uncharacterized protein | A0A3Q1M3L6 | 4 | 1.5 |
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D’Souza, K.; Mercer, A.; Mawhinney, H.; Pulinilkunnil, T.; Udenigwe, C.C.; Kienesberger, P.C. Whey Peptides Stimulate Differentiation and Lipid Metabolism in Adipocytes and Ameliorate Lipotoxicity-Induced Insulin Resistance in Muscle Cells. Nutrients 2020, 12, 425. https://doi.org/10.3390/nu12020425
D’Souza K, Mercer A, Mawhinney H, Pulinilkunnil T, Udenigwe CC, Kienesberger PC. Whey Peptides Stimulate Differentiation and Lipid Metabolism in Adipocytes and Ameliorate Lipotoxicity-Induced Insulin Resistance in Muscle Cells. Nutrients. 2020; 12(2):425. https://doi.org/10.3390/nu12020425
Chicago/Turabian StyleD’Souza, Kenneth, Angella Mercer, Hannah Mawhinney, Thomas Pulinilkunnil, Chibuike C. Udenigwe, and Petra C. Kienesberger. 2020. "Whey Peptides Stimulate Differentiation and Lipid Metabolism in Adipocytes and Ameliorate Lipotoxicity-Induced Insulin Resistance in Muscle Cells" Nutrients 12, no. 2: 425. https://doi.org/10.3390/nu12020425