Research Article| Volume 121, P30-39, June 2017

Dietary Salba (Salvia hispanica L) improves the altered metabolic fate of glucose and reduces increased collagen deposition in the heart of insulin-resistant rats


      • Chia seeds improve lipotoxicity and glucose metabolism of insulin-resistant rat heart.
      • Mechanisms involved in the altered cardiac glucose fate are improved by chia seeds.
      • Beneficial effects of chia seeds on hypertension and cardiac collagen deposition.


      This study reports the effects of dietary Salba (chia) seeds on the mechanisms underlying impaired glucose metabolism in the heart of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD). Wistar rats were fed a SRD for 3 months. Afterwards, half the animals continued with the SRD; in the other half's diet chia seeds replaced corn oil (CO) for three months (SRD+chia). In the control group, corn starch replaced sucrose. The replacement of CO by chia seeds in the SRD restored the activities of key enzymes involved in heart glucose metabolism decreasing fatty acid oxidation. Chia seeds normalized insulin stimulated GLUT-4 transporter, the abundance of IRS-1 and pAMPK, changed the profile of fatty acid phospholipids, reduced left-ventricle collagen deposition and normalized hypertension and dyslipidemia. New evidence is provided concerning the effects of dietary chia seeds in improving the altered metabolic fate of glucose in the heart of dyslipemic insulin-resistant rats.


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        • Bruce K.D.
        • Hanson M.A.
        The developmental origins, mechanisms, and implications of metabolic syndrome.
        J. Nutr. 2010; 140: 648-652
        • Zhou Y.T.
        • Grayburn P.
        • Karim A.
        • Shimabukuro M.
        • Higa M.
        • Baetens D.
        • Orci L.
        • Unger R.H.
        Lipotoxic heart disease in obese rats: implications for human obesity.
        Proc. Natl. Acad. Sci. USA. 2000; 97: 1784-1789
        • Randle P.J.
        • Newsholmet E.A.
        • Garland P.B.
        Regulation of glucose uptake by muscle 8.
        Biochem. J. 1964; 93: 652-665
        • Hue L.
        • Taegtmeyer H.
        The Randle cycle revisited: a new head for an old hat.
        AJP Endocrinol. Metab. 2009; 297: E578-E591
        • Neves F.A.
        • Cortez E.
        • Bernardo A.F.
        • Mattos A.B.M.
        • Vieira A.K.
        • Malafaia T.O.
        • Thole A.A.
        • Alessandra A.C.
        • Garcia-Souza É.P.
        • Sichieri R.
        • Moura A.S.
        Heart energy metabolism impairment in western-diet induced obese mice.
        J. Nutr. Biochem. 2014; 25: 50-57
        • Bonen A.
        • Holloway G.P.
        • Tandon N.N.
        • Han X.
        • McFarlan J.
        • Glatz J.F.C.
        • Luiken J.J.F.P.
        Cardiac and skeletal muscle fatty acid transport and transporters and triacylglycerol and fatty acid oxidation in lean and Zucker diabetic fatty rats.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009; 297: R1202-R1212
        • Ménard S.L.
        • Croteau E.
        • Sarrhini O.
        • Gélinas R.
        • Brassard P.
        • Ouellet R.
        • Bentourkia M.
        • van Lier J.E.
        • Des Rosiers C.
        • Lecomte R.
        • Carpentier A.C.
        Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats.
        Am. J. Physiol. Endocrinol. Metab. 2010; 298: E1049-E1057
        • Chatham J.C.
        • Seymour A.M.
        Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.
        Cardiovasc Res. 2002; 55: 104-112
        • Hein G.J.
        • Bernasconi A.M.
        • Montanaro M.A.
        • Pellon-Maison M.
        • Finarelli G.
        • Chicco A.
        • Lombardo Y.B.
        • Brenner R.R.
        Nuclear receptors and hepatic lipidogenic enzyme response to a dyslipidemic sucrose-rich diet and its reversal by fish oil n-3 polyunsaturated fatty acids.
        Am. J. Physiol. Endocrinol. Metab. 2010; 298: E429-E439
        • Chicco A.
        • Basabe J.C.
        • Karabatas L.
        • Ferraris N.
        • Fortino A.
        • Lombardo Y.B.
        Troglitazone (CS-045) normalizes hypertriglyceridemia and restores the altered patterns of glucose-stimulated insulin secretion in dyslipidemic rats.
        Metabolism. 2000; 49: 1346-1351
        • Poudyal H.
        • Panchal S.K.
        • Ward L.C.
        • Waanders J.
        • Brown L.
        Chronic high-carbohydrate, high-fat feeding in rats induces reversible metabolic, cardiovascular, and liver changes.
        Am. J. Physiol. - Endocrinol. Metab. 2012; 302: E1472-E1482
        • Chicco A.
        • Soria A.
        • Fainstein-Day P.
        • Gutman R.
        • Lombardo Y.B.
        Multiphasic metabolic changes in the heart of rats fed a sucrose-rich diet.
        Horm. Metab. Res. 1994; 26: 397-403
        • Montes M.
        • Chicco A.
        • Lombardo Y.B.
        The effect of insulin on the uptake and metabolic fate of glucose in isolated perfused hearts of dyslipemic rats.
        J. Nutr. Biochem. 2000; 11: 30-37
        • Jump D.B.
        • Depner C.M.
        • Tripathy S.
        Omega-3 fatty acid supplementation and cardiovascular disease.
        J. Lipid Res. 2012; 53: 2525-2545
        • Djoussé L.
        • Arnett D.K.
        • Pankow J.S.
        • Hopkins P.N.
        • Province M.A.
        • Curtis Ellison R.
        Dietary linolenic acid is associated with a lower prevalence of hypertension in the NHLBI family heart study.
        Hypertension. 2005; 45: 368-373
        • Barceló-Coblijn G.
        • Murphy E.J.
        Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels.
        Prog. Lipid Res. 2009; 48: 355-374
        • Marineli R. da S.
        • Moraes E.A.
        • Lenquiste S.A.
        • Godoy A.T.
        • Eberlin M.N.
        • Marostica M.R.
        Chemical characterization and antioxidant potential of Chilean chia seeds and oil (Salvia hispanica L.).
        LWT - Food Sci. Technol. 2014; 59: 1304-1310
        • Valdivia-Lopez M.A.
        Chia (Salvia hispanica): a review of native Mexican seed and its nutritional and functional properties.
        Adv. Food Nutr. Res. 2015; 75: 53-75
        • Vuksan V.
        • Jenkins A.
        • Dias A.
        • Lee A.
        • Jovanovski E.
        • Rogovik A.
        • Hanna A.
        Reduction in postprandial glucose excursion and prolongation of satiety: possible explanation of the long-term effects of whole grain Salba (Salvia hispanica L.).
        Eur. J. Clin. Nutr. 2010; 64: 436-438
        • Vuksan V.
        • Dana W.
        • Sievenpiper J.L.
        • Jenkins A.L.
        • Rogovik A.L.
        • Bazinet R.P.
        • Vidgen E.
        • Hanna A.
        Supplementation of conventional therapy with the novel grain salba (Salvia hispanica L.) improves major and emerging cardiovascular risk factors in type 2 diabetes.
        Diabetes Care. 2007; 30: 2804-2810
        • Ho H.
        • Lee A.S.
        • Jovanovski E.
        • Jenkins A.L.
        • DeSouza R.
        • Vuksan V.
        Effect of whole and ground Salba seeds (Salvia hispanica L.) on postprandial glycemia in healthy volunteers: a randomized controlled, dose-response trial.
        Eur. J. Clin. Nutr. 2013; 67: 786-788
        • Creus A.
        • Ferreira M.R.
        • Oliva M.E.
        • Lombardo Y.B.
        Mechanisms involved in the improvement of lipotoxicity and impaired lipid metabolism by dietary α-linolenic acid rich salvia hispanica L (Salba) seed in the heart of dyslipemic insulin-resistant rats.
        J. Clin. Med. 2016; 5: 1-18
        • Oliva M.E.
        • Ferreira M.R.
        • Chicco A.
        • Lombardo Y.B.
        Dietary salba (salvia hispanica L) seed rich in alpha-linolenic acid improves adipose tissue dysfunction and the altered skeletal muscle glucose and lipid metabolism in dyslipidemic insulin-resistant rats.
        Prostaglandins Leukot. Essent. Fat. Acids. 2013; 89: 279-289
        • D’Alessandro M.E.
        • Chicco A.
        • Lombardo Y.B.
        Dietary fish oil reverses lipotoxicity, altered glucose metabolism, and nPKCε translocation in the heart of dyslipemic insulin-resistant rats.
        Metabolism. 2008; 57: 911-919
        • Folch J.
        • Lees M.
        • Stanley G.H.S.
        A simple method for the isolation and purification of total lipids from animal tissues.
        J. Biol. Chem. 1957; 226: 497-509
        • Ferreira M.R.
        • Alvarez S.M.
        • Illesca P.
        • Gimenez M.S.
        • Lombardo Y.B.
        Dietary Salba (Salvia hispanica L.) ameliorates the adipose tissue dysfunction of dyslipemic insulin-resistant rats through mechanisms involving oxidative stress, inflammatory cytokines and peroxisome proliferator-activated receptor γ.
        Eur. J. Nutr. 2016; : 1-12
        • Bezerra R.M.
        • Ueno M.
        • Silva M.S.
        • Tavares D.Q.
        • Carvalho C.R.
        • Saad M.J.
        A high fructose diet affects the early steps of insulin action in muscle and liver of rats.
        J. Nutr. 2000; 130: 1531-1535
        • Neuman R.E.
        • Logan M.A.
        The determination of hydroxyproline.
        J. Biol. Chem. 1950; 184: 299-306
        • Black M.J.
        • D’Amore A.
        • Auden A.
        • Stamp L.
        • Osicka T.
        • Panagiotopoulos S.
        • Jerums G.
        Chronic type 1 diabetes in spontaneously hypertensive rats leads to exacerbated cardiac fibrosis.
        Cardiovasc. Pathol. 2010; 19: 361-370
        • Glantz S.A.
        Pimer of Biostatistics. 6th ed. McGraw Hill, New York2005
        • Snedecor G.W.
        • Cochran W.G.
        Statistical Methods Applied to Experiments in Agriculture and Biology.
        6th ed. Iowa State University Press, Ames1967
        • Desrois M.
        • Sidell R.J.
        • Gauguier D.
        • King L.M.
        • Radda G.K.
        • Clarke K.
        Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart.
        Cardiovasc Res. 2004; 61: 288-296
        • Thompson A.L.
        • Cooney G.J.
        Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance.
        Diabetes. 2000; 49: 1761-1765
        • Holness M.J.
        • Sugden M.C.
        Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation.
        Biochem. Soc. Trans. 2003; 31: 1143-1151
        • Gray S.
        • Kim J.K.
        New insights into insulin resistance in the diabetic heart.
        Trends Endocrinol. Metab. 2011; 22: 394-403
        • Rossi A.S.
        • Oliva M.E.
        • Ferreira M.R.
        • Chicco A.
        • Lombardo Y.B.
        Dietary chia seed induced changes in hepatic transcription factors and their target lipogenic and oxidative enzyme activities in dyslipidaemic insulin-resistant rats.
        Br. J. Nutr. 2012; : 1-11
        • González-Mañán D.
        • Tapia G.
        • Gormaz J.G.
        • D’Espessailles A.
        • Espinosa A.
        • Masson L.
        • Varela P.
        • Valenzuela A.
        • Valenzuela R.
        Bioconversion of α-linolenic acid to n-3 LCPUFA and expression of PPAR-alpha, acyl coenzyme A oxidase 1 and carnitine acyl transferase I are incremented after feeding rats with α-linolenic acid-rich oils.
        Food Funct. 2012; 3: 765-772
        • Longnus S.L.
        • Ségalen C.
        • Giudicelli J.
        • Sajan M.P.
        • Farese R.V.
        • Van Obberghen E.
        Insulin signalling downstream of protein kinase B is potentiated by 5′AMP-activated protein kinase in rat hearts in vivo.
        Diabetologia. 2005; 48: 2591-2601
        • Dyck J.R.B.
        • Lopaschuk G.D.
        AMPK alterations in cardiac physiology and pathology: enemy or ally?.
        J. Physiol. 2006; 574: 95-112
        • Gamble J.
        • Lopaschuk G.D.
        Insulin inhibition of 5’ adenosine monophosphate-activated protein kinase in the heart results in activation of acetyl coenzyme A carboxylase and inhibition of fatty acid oxidation.
        Metabolism. 1997; 46: 1270-1274
        • Samovski D.
        • Sun J.
        • Pietka T.
        • Gross R.W.
        • Eckel R.H.
        • Su X.
        • Stahl P.D.
        • Abumrad N.A.
        Regulation of AMPK activation by CD36 links fatty acid uptake to b-oxidation.
        Diabetes. 2015; 64: 353-359
        • Weber K.T.
        Fibrosis and hypertensive heart disease.
        Curr. Opin. Cardiol. 2000; 15: 264-272
        • Poudyal H.
        • Panchal S.K.
        • Ward L.C.
        • Brown L.
        Effects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.
        J. Nutr. Biochem. 2013; 24: 1041-1052
        • Ogawa A.
        • Suzuki Y.
        • Aoyama T.
        • Takeuchi H.
        Dietary alpha-linolenic acid inhibits angiotensin-converting enzyme activity and mRNA expression levels in the aorta of spontaneously hypertensive rats.
        J. Oleo Sci. 2009; 58: 355-360
        • Folino A.
        • Sprio A.E.
        • Di Scipio F.
        • Berta G.N.
        • Rastaldo R.
        Alpha-linolenic acid protects against cardiac injury and remodelling induced by beta-adrenergic overstimulation.
        Food Funct. 2015; 6: 2231-2239
        • Yan L.
        • Zhang J.D.
        • Wang B.
        • Lv Y.J.
        • Jiang H.
        • Liu G.L.
        • Qiao Y.
        • Ren M.
        • Guo X.F.
        Quercetin inhibits left ventricular hypertrophy in spontaneously hypertensive rats and inhibits angiotensin II-induced H9C2 cells hypertrophy by enhancing PPAR-γ expression and suppressing AP-1 activity.
        PLoS One. 2013; 8 (e72548 1-14)
        • Panchal S.K.
        • Poudyal H.
        • Brown L.
        Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats.
        J. Nutr. 2012; 142: 1026-1032
        • Vuksan V.
        • Choleva L.
        • Jovanovski E.
        • Jenkins A.L.
        • Au-Yeung F.
        • Dias A.G.
        • Ho H.V.T.
        • Zurbau A.
        • Duvnjak L.
        Comparison of flax (Linum usitatissimum) and Salba-chia (Salvia hispanica L.) seeds on postprandial glycemia and satiety in healthy individuals: a randomized, controlled, crossover study.
        Eur. J. Clin. Nutr. 2016; : 1-5
        • Poudyal H.
        • Panchal S.K.
        • Waanders J.
        • Ward L.
        • Brown L.
        Lipid redistribution by α-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats.
        J. Nutr. Biochem. 2012; 23: 153-162
        • Valenzuela B.R.
        • Barrera R.C.
        • Gonzalez-Astorga M.
        • Sanhueza C.J.
        • Valenzuela B.A.
        • Tapia G.O.
        Alpha linolenic acid (ALA) from Rosa canina, sacha inchi and chia oils may increase ALA accretion and its conversion into n-3 LCPUFA in diverse tissues of the rat.
        Food Funct. 2014; 5: 356-367
        • Storlien L.H.
        • Jenkins A.B.
        • Chisholm D.J.
        • Pascoe W.S.
        • Khouri S.
        • Kraegen E.W.
        Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid.
        Diabetes. 1991; 40: 280-289
        • Echeverría F.
        • Ortiz M.
        • Valenzuela R.
        • Videla L.A.
        Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: relationship to tissue development and aging.
        Prostaglandins Leukot. Essent. Fat. Acids. 2016; 114: 28-34
        • Vuksan V.
        • Jenkins A.L.
        • Brissette C.
        • Choleva L.
        • Jovanovski E.
        • Gibbs A.L.
        • Bazinet R.P.
        • Au-Yeung F.
        • Zurbau A.
        • Ho H.V.T.
        • Duvnjak L.
        • Sievenpiper J.L.
        • Josse R.G.
        • Hanna A.
        Salba-chia (Salvia hispanica L.) in the treatment of overweight and obese patients with type 2 diabetes: a double-blind randomized controlled trial.
        Nutr. Metab. Cardiovasc. Dis. 2017; 27: 138-146