R , L.), which ˆ ancio ıcius P. Ven ´ hispanica ,Vin 2020 Institute of Food Technologists Further reproduction without permission is prohibited C ´ ucio L ´ oska, 2016). The search for mechanisms ,HairaG.L ´ e, & Blais, 2017). Well-planned animal studies are .) effects and their These components present in chia have been considered A food alternative is ( In the current context of increased obesity and comorbidities, 2013), used by(Ayerza, Pre-Colombian 2009). This populations seed asalpha is linolenic nutritional known acid for food (ALA) itsvitamins, omega high 3 minerals, concentration (n-3), and of dietarypounds phytochemicals, fiber, (da , such Silva et as al., phenolic 2017; Marineli com- et al.,responsible 2014). for theto improvement diseases, of presenting biological properties, markers including related anti-inflammatory through which bioactive compounds would improveand obese health decrease comorbidities riskunbalanced diets, has since increased it is animaltake a pattern studies way that to fed contributes mitigateinvolving to the Rodents overweight. human Experimental are food widely studies in- usedsince their in physiology is the similar nutrition to human’s,nal research including (Hatton, gastrointesti- field Yadav, Basit, & Merchant,be 2015). considered Animal an studies important can and screening their for different testing doses newgation and into plant fractions, molecular food attempting pathways using a tissues,to deep which accomplish is investi- not in possible researchBlachier, involving Tom humans (Chalvon-demersay, considered a stepwhich before can treatment be more application successfuldesign in when efficient previous outcomes clinical data (Everitt, trials, are 2015). available to belongs to Salvia genus (Arctosto Specimen northern Database, 2018), native and southern (Busilacchi et al., plant food has been investigated as athat source of might bioactive compounds act asdiseases a (Borowska coadjutant & in Brz the prevention and treatment of , Mariana Grancieri ercia´ S. D. Martino ,andH ´ arbara P. Silva ,B ¸osa, MG 36570-900, Brazil. Authors Vol. 85, Iss. 2, 2020 doi: 10.1111/1750-3841.15003 , Carla O. B. Rosa r Salvia hispanica L The consumption of chia may improve lipid profile, insulin and glucose tolerance, and ¸osa, Vic ´ ucio, Rosa, and Martino are with Dept. of Nutrition , Luiza P. D. Moreira The aim of this review was to compile evidence and understand chia seed effects on unbalanced diet animal alpha linolenic acid, chia seed, dyslipidemia, glucose tolerance,

Journal of Food Science

effects of the seed. Sample size, chia dose, and numberthe of studies. animals evaluated Based for on eachrisk parameter experimental of were chronic found study disease to data, development, be mainly chia lacking due information has to among the bioactive antioxidant, potential, anti-inflammatory, hypoglycemic, and and hypolipidemic its daily consumption may reduce the electronic databases, following PRISMA recommendations. RiskARRIVE of guidelines. bias and Seventeen quality articles wasAMPK were assessed modulation: included. using SYRCLE improvement Throughout of toll the and Details glucose studies, about and chia’s randomization insulin main and tolerance, effects allocation lipogenesis, are concealment antioxidant were associated activity, insufficient, with and as inflammation. well as information about blind protocols. studies and the molecular mechanisms on metabolic biomarker modulation. A systematic review was conducted in than the seed. reduce risk of . Whole seed or its oil presents positive effect, but the effects of chia oil can act faster Practical Application: Keywords: Abstract: ˆ ancio and Mertens-Talcott are with Dept. of Nutrition and Food Science, Texas The “western diet” is considered an unbalanced diet, since the Noncommunicable diseases, such as cardiovascular diseases, can- ´ arbara N. Enes JFDS-2019-0214 Submitted 1/30/2019, Accepted 11/22/2019. Authors Enes, Susanne U. Mertens-Talcott morbidities, such as insulin resistance (IR), typeand 2 diabetes cardiovascular mellitus, diseases (Pozza & Isidori, 2018). which is associated with increasedflammation, oxidative and stress major and biochemical and chronic metabolic in- trigger changes, which a series of events associated with the development of co- macronutrients distribution isments not (Institute of Medicine, adequate 2005). Sedentary toanced lifestyle diets and lead human to unbal- overweight (World require- Health Organization, 2017), diet,” characterized by highrefined intakes , of and ,2011; added animal-source Popkin, foods, sugar. Nielsen, & (Popkin, Bray, 2004). Adair, & Ng, tors that may contribute toindicated weight excess, strong epidemiological correlation studies betweenfructose, and the saturated lipids––high consumption content of productsThis with pattern sugar, obesity. of food consumption is often termed as the “western cer, and diabetes, areworld (Wang responsible et for al., threeblood 2016). in pressure, These five high diseases deaths , areobesity in derived and (World Health from the ultimately Organization, high overweight 2017). and Among various fac- 226 B experimental studies: A systematic review Chia seed ( molecular mechanisms on unbalanced diet 1. INTRODUCTION A&M Univ., College Station, TX(E-mail: 77843, [email protected]). USA. Direct inquiries to author Martino Moreira, Silva, Grancieri,and L Health, FederalVen Univ. of Vic

Concise Reviews & Hypotheses in Food Science nasadrie oe fdt extraction. data of summarized model was standardized pathway information a protocol, This in chia study results. study, model, main the and animal of investigated, date, duration dose, publication and authors, fraction information study: relevant extracted each reviewers from by The followed screening. first, and examined text were identity full abstracts author and in to Titles blinded described origin. not study (as were independently who criteria two reviewers by working inclusion performed was extraction the data 2.1), fulfilled dis- Section consensus. Any that through consumption. studies resolved chia For were of of reviewers effect between eligibility the crepancies the evaluated assessed that independently studies researchers two 2009), context. diet healthy that those a and in chia, seed those as chia treatment seeds, used same chia the in containing foods We mixtures other diet). involving used (standard group that control studies a excluded have and should group of protocol diet study de- regardless unbalanced the review, an experimental this both), or in or included used, be To fiber, concentration sign. or (oil, dose fractions duration, their study with and conducted studies seeds original chia metabolic included improves results seed The mecha- chia the parameters. which investigating through of pathways purpose and of our nisms reason on The based studies. was animal choice for available, that Table if in used, presented were is Filters databases S1. electronic the in search employed Full strategy steatohepatitis”). “nonalcoholic OR disease” liver “nonalcoholic fatty OR syndrome” “metabolic OR Diseases” “Cardiovascular Hypertension OR OR OR Dyslipidemias diabetes OR OR (obesity Resistance” AND Inflammation “Insulin L.”) OR hispanica (“chia Hyperglycemia “salvia database: OR OR each seeds” in “chia search OR to Direct. seed” used were Science terms following and The Embase, Information Sciences PubMed/MEDLINE, Health (LILACS), on Center Caribbean and American been has (www.crd.york.ac.uk/prospero/): review PROSPERO CRD42019119667. The the 2009). at al., Meta- registered et and Reviews (Liberati Systematic (PRISMA) for Analysis Items Reporting Preferred to . td eeto n aacleto process collection data and selection Study 2.3 search Literature 2.2 registration and Protocol 2.1 METHODS 2. biomarker understand metabolic to on modulation. mechanisms and molecular studies the and animal effects diet the unbalanced on effects seed unknown. the remain ben- in seeds health involved chia pathways by its and diseases for of mechanisms responsible chemoprevention the synergic is that, a compound Besides in specific efits. acting a them, if between interaction or, an way is un- there (Toscano, remains if hypocholesterolemic it clear Though al., and 2015). Silva, et 2017), & (Vuksan Oliveira, Tavares, al., Toscano, hypoglycemic et 2014), Vuksan al., 2010; hy- Zarshenas, 2016), et Rosa, (Toscano & & potensive Prestes, Schmidt, Sohrabpour, (Scapin, antioxidant Ahmadi, 2016), Jamshidzadeh, (Hamedi, . . . diet unbalanced on effects seed Chia olwn h eomnain fPIM Lbrt tal., et (Liberati PRISMA of recommendations the Following Latin databases: electronic searching by identified were Studies according reported and out carried was review systematic This hs h i fti eiwwst opl vdneo chia of evidence compile to was review this of aim the Thus, a vlae n o ahciein 0 r“”wsgae for graded the was calculated. and “1” respectively, was or information, frequency “reported” “0” studies and included criterion, reported” the biol- each “not of human for Each to study. and relevance the evaluated the of and was limitations as study the well the and as in ogy results, involved of methods report discussion the the the of to conclusion attention the special to the which with title improve criteria, the 20 from and of everything consists standardize evaluate It studies. to animal reporting intended of quality are guidelines guidelines AR- The RIVE (ARRIVE) 2010). Altman, Experiment & Re- Vivo Emerson, Animal Cuthill, Browne, (Kilkenny, in the using of assessed Reporting was more search studies included or the one of quality (?, “unclear” or attended), attended). were partly were criteria criteria all if (–, . ult assessment Quality 2.4 . nlddsuisadcharacteristics and studies Included 3.1 DISCUSSION AND RESULTS 3. tes o ahicue td,tesxba ye eeclassified were types bias six ( the “high” study, as included bias, and selection each bias, bias: reporting For of bias, others. types attrition con- bias, six detection to toll bias, related RoB performance are SYRCLE that The entries an- 2011). 10 involving al., siders bias et the (Higgins measure studies to the imal and on quality based method developed was evaluate is tool to which RoB 2014), SYRCLE The (SYR- al., Collaboration. Bias et Cochrane (Hooijmans of tool Risk RoB) Experimentation CLE Animal Laboratory for tre ta. 08 otn,Oia orge,Lmad,&Chicco, Moraes, Lenquiste, & Marineli, Lombardo, 2015; &Mar al., Rodriguez, et Moura, Oliva, Silva Marineli, Fortino, da 2017; 2016; 2018; Lombardo, al., & Oliva, et Ferreira, Villafa Creus, Benmelej, 2017; Creus, bardo, 2009; Lombardo, & rodents: Oliva, with conducted were Alar- others Wistar Roco, The as 2015). (Sierra, one Medina, rabbits chia only & hybrid records, of con, Flanders included use with 17 of conducted From was 1). absence (Figure and treatment review chia, study were of excluded properties to records related technological studies Most research, included. characterization chemical studies adding the publications, snowballing 17 During by review. to identified the this was up all study in one attended included reading, studies were full-text and 16 19 full-text reading, criteria step, for full-text inclusion this retrieved were the after criteria From and inclusion reading. abstracts the was and met studies titles that remaining studies their the reading of by selection made The removed. were cates ad ta. 09,adtehgetds,4.% a bet increase to Mi- able was (de 41.7%, dose, animals highest the and the 2019), al., of et high- randa (HDL-c) between the increase cholesterol varied to able dose lipoprotein was the 3%, density dose, and lowest The seed 41.7%. used and chia 3% the used Regarding studies pathway. 11 atherosclerosis fractions, the one an- and analyzed the inflammation, study the analyzed analyzed studies studies three five effects, pathway, tioxidant lipogenesis the evaluated (Rui, 2018). mice Wan, SAMR1/SAMP8 & and Qin, 2019), Chen, Swiss Yang, al., 2019), et al., Miranda et (de (Fonte-Faria mice Waanders, mice Ward, C57BL/6 Panchal, 2012), Poudyal, Brown, & 2013; Brown, & Ward, chal, Pan- Poudyal, 2012; Brown, & Ward, Waanders, Panchal, Poudyal, oices h tegho h rsn ytmtcrve,the review, systematic present the of strength the increase To h iko iswsasse sn h ytmtcRve Cen- Review Systematic the using assessed was bias of risk The h erhyeddattlo 6 eod rmwih1 dupli- 17 which from records 165 of total a yielded search The oa fnn tde vlae lcs eaoim 0studies 10 metabolism, glucose evaluated studies nine of total A sia 05 lv,Frer,Cic,&Lmad,2013; Lombardo, & Chicco, Ferreira, Oliva, 2015; ostica, as(yra&Cae,20;Cic,DAesnr,Hein, D’Alessandro, Chicco, 2007; Coates, & (Ayerza rats ´ + foeo oeciei eentatne) “low” attended), not were criteria more or one if , o.8,Is ,2020 2, Iss. 85, Vol. r ora fFo Science Food of Journal e Lom- & ne, ˜ 227

Concise Reviews & Hypotheses in Food Science Although there are published clinical trials with chia seeds, this type 4 (GLUT-4) translocation toduced plasma the membrane, serum and also fastingTreatment re- duration insulin varied between levels 3 (Fonte-Faria andobserved et 24 positive weeks al., and effects 2019). all of studies highest known chia amount seeds of n-3, or(Ayerza ranged & oil. between 64.8% Coates, Chia and 2011), seedsults 56.9% which has found may in the explain animalpresented the in studies. Table promising A 1. re- summary of each publicationreview included is only animal studies. Ourpurpose, choice which was based was on to our through investigate which the mechanisms chia andof seed pathways the improves metabolic clinical parameters. trial Most results are limited to improvement on lipid Vol. 85, Iss. 2, 2020 r B expression), and decrease cholesterol (da Silva κ Journal of Food Science Six studies used chia oil and the doses varied between 0.15% and 228 10%. The lowest concentration (0.15%)IR, had as effects increased that glucose improved andceptor insulin substrate tolerance induced (IRS) insulin phosphorylation re- and glucose transporter (Arvola et al.,bioactive 2007) antioxidant, such and as phenolic the acids tohealth grinding cells benefits which (Rosa, allows increase Dufour, bioaccessibility Lullien-pellerin, of & Micard, 2013). particle size acts(Slavin, 2003). directly Furthermore, on the wholeponent digestion seed present flour and in has the every metabolic , com- like processes endosperm, bran, germ, and coat the antioxidant capacity, decrease thetokines and inflammatory NF- markers (cy- et al., 2018). The whole seed was offered to animals as flour since Figure 1–Flowchart of the search and selection process for articles included in the systematic review, according to PRISMA recommendation. Chia seed effects on unbalanced diet . . .

Concise Reviews & Hypotheses in Food Science Table 1–Characteristics of the animal studies. . . . diet unbalanced on effects seed Chia

Fraction and References Animal model Study protocol dose Study duration Pathway Main results Fonte-Faria et al. C57 BL/6 mice, Control (n = 8) Chia oil 19 weeks Glucose metabolism ↑ Glucose and insulin tolerance (2019) male HFD (n = 8) 0.15% Insulin signaling ↓ Serum fasting insulin levels HFD (n = 8) followed by HFD + ↓ Serum leptin chia oil ↓ Serum TG ↑ HDLc ↓ Body mass and ↑ Body lean mass ↑ pIRS-1(Tyr)/IRS-1 ↑ GLUT-4 translocation to plasma membrane da Silva et al. (2018) Wistar rats, male Control + carbonate (n = 8) Chia seed 5 weeks Antioxidant status ↓ Total LDLc and VLDLc cholesterol Control + chia seed (n = 8) 41.3% Inflammation ↑ SOD activity (liver) HFD + calcium carbonate (n = 8) ↑ CAT (plasma) HFD + chia seed (n = 8) ↑ PPAR-α ↓ NFκB mRNA expression ↓ NFκB (liver) ↓ TNF and IL-10 de Miranda et al. Swiss mice Control (n = 6) Chia seed 16 weeks Glucose metabolism Did not modify glucose metabolism (2019) Control + chia seed (n = 6) 3% Antioxidant status ↑ HDLc HFD (n = 6) Lipogenesis HFD + chia seed (n = 6) Inflammation

Rui et al. (2018) SAMR1 mice SAMR1 LFD (n = 8) Chia seed 18 weeks Glucose metabolism ↓ Insulin (plasma) SAMP8 mice SAMP8 LFD (n = 8) 10% ↓ HOMA-IR SAMP8 HFD (n = 8) SAMP8 HFD + chia seed (n = 8)

Creus et al. (2017) Wistar rats, male Control (n = 24) Chia seed 24 weeks AMPK ↓ pAMPK/AMPK SRD (n = 24) 36.2% Glucose metabolism ↓ TG, FFA, glucose (plasma) SRD (n = 24) followed by SRD + ↑ G-6-P, glycogen (heart muscle) chia seed ↑ Hexokinase and PDHa activities (heart muscle) ↑ GLUT-4, IRS-1 (heart muscle) o.8,Is ,2020 2, Iss. 85, Vol. ↓ Collagen and hydroxyproline contents in left ventricle ↓ SBP Fortino et al. (2017) Wistar rats, male Male offspring of RD-fed dams: Chia seed 20 weeks Glucose metabolism ↓ TC, TG (plasma) RD-RD (control) 20% Lipogenesis ↓ n6:n3 ratio Male offspring of SRD-fed dams: ↑ CPT-1 SRD-SRD (n = 30) ↓ ACC

r SRD-SRD Chia seed (n = 30) ↓ Glucose (plasma) ora fFo Science Food of Journal ↑ Glucose tolerance ↓ SBP and DBP Ferreira et al. (2016) Wistar rats, male Control (n = 24, 24 weeks) Chia seed 12 weeks Antioxidant status ↓ Epididymal fat and ↑ PPAR-γ (epididymal SRD (n = 24, 24 weeks) 36.2% Lipogenesis fat) SRD (n = 24) followed by SRD + Inflammation ↓ TG, FFA, uric acid, glucose, n3:n6 ratio chia seed (plasma), and ↑ GIR ↓ TNF, IL-6 (plasma) ↓ TBARS, carbonyl groups, XO activity, and ROS ↑ GPx and SOD activity ↑ 229 Nrf2 mRNA (Continued)

Concise Reviews & Hypotheses in Food Science

) Continued (

SBP ↑

S,LH L,CK ALP, LDH, AST, ↓

erprtna dps tissue) adipose retroperitoneal

3n hat ie,seea muscle, skeletal liver, (heart, n3:n6 ↑

lcs n nui tolerance insulin and Glucose ↑

nui (plasma) Insulin ↓

C G n EA(plasma) NEFA and TG, TC, ↓

12) n ( oil muscle =

Chia HFHF by followed HFHF ii otn nlvr er,adskeletal and heart, liver, in content Lipid + ↓

12) n ( HFHF ie weight Liver = ↓

12) n ( oil tissue =

3% chia control by followed Control icmeec,adrtoeioeladipose retroperitoneal and circumference, +

Wistar (2013) al. et Poudyal 6wesLipogenesis weeks 16 oil Chia 12) n ( Control male rats, icrlaioiy() abdominal (%), adiposity Visceral = ↓

gsrceismuscle) (gastrocnemius

G ogcanay o,adDG and CoA, acyl long-chain TG, ↓

eoiae Da(atonmu muscle) (gastrocnemius PDHa Hexokinase, ↑

A,GP,mlcenzyme malic G6PD, FAS, ↓

haseed chia G(adipocyte) TG ↓

)floe ySRD by followed 6) n ( SRD pddmlAT Epididymal + = ↓

6) n ( SRD GIR = ↑

hase 4wesGuoemetabolism Glucose weeks 24 seed Chia G F,guoe(plasma) glucose FFA, TG, Wistar (2013) al. et Oliva 6) n ( Control male rats, ↓ =

8) n ( 1% cholesterol oil Chia nitni Iadnoradrenaline and II Angiotensin = + ↓

8) n ( 1% cholesterol Control nohlu relaxation Endothelium = + ↑

rabbits 10% 8) n ( oil Chia L (plasma) ALA = ↑

Flanders (2015) al. et Sierra ek Atherosclerosis weeks 6 oil Chia 8) n ( Control hybrids G(plasma) TG = ↓

6) n ( oil chia HFHF L AST e ALT = + ↓

6) n ( seed chia HFHF NEFA = + ↓

6) n ( oil xrsino PGC-1 of Expression = α ↑

chia HFHF by followed HFHF TAC + ↑

6) n ( seed 2weeks 12 4% O n GPx and SOD = ↑

chia HFHF by followed HFHF ogtreatment: Long oil Chia S6 seea muscle) (skeletal HSP60 Lipogenesis + ↓

FF( HFHF 6) n 13.3% lcs metabolism Glucose weeks 6 xrsino S7,HSP25 HSP70, of Expression ta.(2015) al. et = ↑

6) n haseed Chia nixdn status Antioxidant treatment: Short lcs n nui tolerance insulin and Glucose aiei Moura, Marineli, as aeCnrl( Control male rats, Wistar = ↑

HFHF 6) n ( oil Chia = +

HFHF 6) n ( seed Chia = +

i ( oil 6) n 8-isoprostane = ↓

FFfloe yHFHF by followed HFHF Chia BR (plasma) TBARS + ↓

ed( seed 6) n 4% 2weeks 12 RP(ie n plasma) and (liver FRAP = ↑

FFfloe yHFHF by followed HFHF Chia haoil Chia ogtreatment: Long R P lvradplasma) and (liver GPx GR, + ↑

ta.(2015) al. et FF( HFHF 6) n 13.3% weeks 6 GSH = ↑

aiei Lenquiste Marineli, as aeCnrl( Control male rats, Wistar 6) n haseed Chia nixdn status Antioxidant treatment: Short A (plasma) TAC = ↑

Vol. 85, Iss. 2, 2020

SBP r ↓

lcs oxidation Glucose ↑

ada lipotoxicity Cardiac ↓

FAT/CD36 ↑

CPT-1 ↑

itaycrillipid) (intramyocardial

haseed chia TG,LCA-CoA,DAG,and PDHa ↓ ↑

0 olwdb SRD by followed 20) n ( SRD G F,coetrl lcs (plasma) glucose cholesterol, FFA, TG, = + ↓

20) n ( SRD 36.2% GIR = ↑

ru ta.(2016) al. et Creus as aeCnrl( Control male rats, Wistar 20) n 4wesLipogenesis weeks 24 seed Chia icrlAioiyIdx(%) Index Adiposity Visceral = ↓

Journal of Food Science eeecsAia oe td protocol Study model Animal References oeSuydrto aha anresults Main Pathway duration Study dose rcinand Fraction

230 Chia seed effects on unbalanced diet . . . al 1–Continued. Table Concise Reviews & Hypotheses in Food Science hase fet nublne it... . . diet unbalanced on effects seed Chia

Table 1–Continued.

Fraction and References Animal model Study protocol dose Study duration Pathway Main results Poudyal, Panchal, Wistar rats, male Control (n = 12) Chia seed 24 weeks Lipogenesis ↓Visceral adiposity (%), retroperitoneal and Waanders, et al. Control + chia (n = 12) 5% Glucose metabolism omental adipose tissue (2012) HFHF (n = 12) ↓ Lipid content in liver and ↑ in heart HFHF + chia seed (n = 12) ↑ TG and ↓ NEFA (plasma) ↑ n3:n6 (plasma and retroperitoneal AT) ↑ Glucose and insulin tolerance ↓ ALT and ↑ ALP ↓ Inflammatory cells in the left ventricle, collagen deposition, diastolic rigidity, fibrosis ↑ SBP Poudyal, Panchal, Wistar rats, male Control (n = 12) Chia seed 8 weeks Lipogenesis ↓ Visceral adiposity (%), body fat (%), abdominal Ward, et al. (2012) Control + Chia seed (n = 12) 5% Glucose metabolism circumference, retroperitoneal and omental HFHF (n = 12) adipose tissue, and ↑ total body lean mass HFHF + Chia seed (n = 12) 8 ↓ Lipid content in skeletal muscle weeks ↑ Lipid content in heart ↑ Glucose and insulin tolerance ↓ Uric acid, LDH, CRP, AST ↑ TG, ALP, and n3:n6 ratio (plasma) ↓ Liver fibrosis ↑ SBP Chicco et al. (2008) Wistar rats, male Experimental design 1: Chia seed Experimental design 1: Lipogenesis ↓Epididymal and retroperitoneal AT Control (n = 24) 36.2% 3 weeks ↓ TG, NEFA, TC (plasma) SRD (n = 24) Experimental design ↓ TG (liver) SRD + chia seed (n = 24) 2: ↓ Glucose Experimental design 2: 20 weeks ↑ Glucose tolerance Control (n = 24) ↑ n3 total SRD (n = 72) divided into three ↓ n6:n3 ratio (plasma)

o.8,Is ,2020 2, Iss. 85, Vol. subgroups: 1. immediately killed (n = 24) 2. SRD (n = 24) 3. SRD + chia seed (n = 24) Ayerza & Coates Wistar rats, male Control (n = 8, 4 weeks) Chia seed: 4 weeks Lipogenesis ↓ TG, total SFA (plasma) (2007) Whole chia seed (n = 8) 16% ↑ HDLc and n3 (plasma) Ground chia seed (n = 8) Chia oil: Chia oil (n = 8) 5.34% r ora fFo Science Food of Journal ↑,increase;↓, decrease; ACC, acetyl-CoA carboxylase; ALA, alpha linolenic acid; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AMPK, adenosine monophosphate-activated protein kinase; AST, aspartate aminotransferase; AT, adipose tissue; CAT, catalase; CK, creatinine; CPT-1, carnitine-palmitoyl transferase-1; CRP, C-reactive protein; DBP, diastolic blood pressure; DG, diacylglyceride; FAS, synthase; FAT/DC36, fatty acid translocase; FFA, free fatty acid; FRAP, ferric reducing ability of plasma; G-6-P, glucose-6-phosphate; G6PD, glucose-6-phosphate dehydrogenase; GIR, glucose infusion rate; GLUT-4, glucose transporter type 4; GPx, glutathione peroxidase; GR, glutathione reductase; GSH, reduced glutathione; HDLc, high-density lipoprotein; HFD, high-fat diet; HOMA-IR, homeostasis model assessment: insulin resistance; HSP25, heat shock protein 25; HSP60, heat shock protein 60; HSP70, heat shock protein 70; IL-10, interleukin 10; IL-6, interleukin 6; IRS-1, insulin receptor substrate 1; LCA-CoA, long-chain acyl-CoA; LDH, lactate dehydrogenase; LDLc, low-density lipoprotein; n3, omega 3; n6, omega 6; NEFA, nonesterified fatty acid; NF-κB, factor nuclear kappa B; Nrf2, nuclear factor (erythroid-derived 2)-like 2; pAMPK, phosphorylation of adenosine monophosphate-activated protein kinase; PDHa, pyruvate dehydrogenase E1 component subunit alpha; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator; pIRS-1(Tyr)/IRS-1, phosphorylation on Tyr989 of IRS-1; PPAR-α, peroxisome proliferator-activated receptor alpha; PPAR-γ , peroxisome proliferator-activated receptor gamma; RD, reference diet; RD-RD, offspring from dams fed a reference diet (RD) and fed the RD after weaning; ROS, reactive oxygen species; SAMP8 HFD, enescence accelerated mouse - fed a high-fat diet; SAMP8 LFD, senescence accelerated mouse- acknowledgments fed a low-fat diet; SAMR1 LFD, senescence-accelerated mouse-resistant 1 – fed a low-fat diet; SBP, systolic blood pressure; SD, standard diet; SFA, saturated fatty acid; SOD, superoxide dismutase; SRD, sucrose rich diet; SRD-SRD, offspring from SRD-fed dams fed an SRD after weaning; SRD-SRDC, offspring from SRD-fed dams fed an SRD+chia after weaning; TAC, total antioxidant capacity; TBARS, thiobarbituric acid reactive substance; TC, total cholesterol; TG, triacylglycerol; TNF-α, tumor necrosis factor alpha; VLDLc, very low-density lipoprotein; XO, xanthine oxidase. 231

Concise Reviews & Hypotheses in Food Science α -linoleic (n-6) fatty protein mass (Creus expression (Marineli, α α α The consumption of chia 3.2.2 Lipid profile and lipolysis. Among plant foods, chia seed is the major source of n-3 (Ayerza, Moreover, the modulation of glucose metabolism markers by Regarding lipogenesis, rats fed a high-fat diet (HFD) had im- Our review allowed us to develop a hypothesis about how chia improved the lipid profile indiets animals (high in fed simple nutritionally carbohydratesin inadequate like saturate sucrose and fat, fructose,plasma high or cholesterol both). These profile2018; results (Creus de are Miranda et related etet al., al., to al., 2019; improving 2016; 2013; Fonte-Faria daerides et Sierra (Ayerza al., Silva et & 2019; Coates, et al., Poudyal 2016; 2007; 2015) al., Creus Chicco et and et al., al., decreasing2017; 2017; 2009; Oliva plasma Fonte-Faria et Creus al., triglyc- et et 2013; al., al.,Poudyal Poudyal, Panchal, 2019; et Waanders, et Fortino al., al., et 2013; 2012; increased al., Sierra the et plasmatic al.,acids, 2015). levels eicosapentaenoic acid Additionally, of (EPA), chia docosahexaenoic n-3 seed acidn-3/saturated (DHA), and fatty acids,2007; and Chicco et n-3/n-6 al., 2009; ratioOliva Creus et (Ayerza et al., al., & 2013; 2017; Poudyal, Panchal, Coates, Fortinoet Waanders, et et al., al., al., 2015). 2017; 2012; Sierra 2009; Ayerza & Coates,being 2005; the da primary Silvato fatty et EPA al., acid and DHA 2017) of has& and the been Galli, despite n-3 widely 2009). held pathway, Studies itsbeen as demonstrating inefficient with conversion that (Ratnayake chia its seed physiologicalthat effects produced as by are a EPA different and than source DHAThey in of also rats showed ALA that with although metabolic have ALA syndrome. total was not body efficient fat in reducing (Poudyal,et Panchal, Waanders, al., et 2013), al., it 2012;dominal has area Poudyal (Fonte-Faria induced et fat al.,Panchal, 2019; redistribution Oliva Waanders, et away et al., from 2013; al., the Poudyal, 2012; ab- 2012; Poudyal et Poudyal, Panchal, al.,diseases. 2013), Ward, et decreasing al., the risk of cardiovascular chia seed had impact onperoxisome lipogenesis, proliferator-activated evidenced receptor by (PPAR) the2016; (Creus increase da et of Silva al., etreduction al., of 2018), visceral improvement inpose adiposity, serum and tissue lipid decrease weight profile, et of (Ayerza epididymal & al., adi- Coates, 2009;et 2007) al., Creus (Figure 2016; et Fortino 2;2015). et Chicco al., al., 2017; 2016; Oliva Creus et al., et 2013;paired Sierra al., et recruitment 2017; al., of Ferreira activity FAT/CD36 by (Creus insulin etet as al., al., well 2016) 2016; as and dachronic CTP-1 PPAR- Silva high et exposure al., toing fatty 2018). the balance These acids between findings provided lipidof oxidation-storage. by are FAT/CD36 The HFD, by related recruitment disrupt- insulin to and is for a key restoring mechanismrevert mitochondrial this for condition activity. beta-oxidation by Chia recruitingthrough FAT/CD36 seed insulin to signaling the was (Creus sarcolemma able et(da al., to Silva 2016), increasing et PPAR- al.,Moura, et 2018), al., increasing 2015), and PGC1- decreasing2016; visceral adiposity Ferreira (Creus et et al., al.,Poudyal 2016; et al., Poudyal, Panchal, 2013). Ward, et al., 2012; seed can improve lipidsulin biomarkers. intolerance Unbalanced and diets this isreversed induce abnormal a in- key glucose event homeostasis forsensitivity and lipogenesis. peripheral (Chicco Chia insulin seed et in- al.,2017; Ferreira 2009; et Creus al., et 2016;2017; Fonte-Faria al., Marineli, et 2016; al., Moura, 2019; Creus et Fortino2015; et Oliva et al., et al., al., 2015; al., 2013; Marineli, Poudyal, Panchal, Lenquiste, Waanders, et et al., al., 2012; ) and HSP ex- α ´ enez, & Lombardo, The introduction of chia to Vol. 85, Iss. 2, 2020 r expression, and peritoneal glucose toler- α coactivator 1-alpha (PGC-1 γ Journal of Food Science From the included studies, we hypothesize that chia and its 3.2.1 Glucose metabolism. AMPK is one of the most important proteins involved to fractions mitigate obesity-induceding insulin AMPK sensitivity and IRS-1 by phosphorylation,translocation regulat- which improve and GLUT-4 increaseenzymatic hexokinase activity and (Chicco glucose etreira al., 6-phosphate et 2009; al., Creus2015; 2016; et Oliva Fortino al., et et 2017; al.,which Fer- al., would 2013; 2017; restore Poudyal, glucose Marineli, Panchal, utilizationhypothesis Moura, as Ward, is et an et supported energetic al., al., by fuel.et the 2012), This al., increase in 2016), CPT-1 PGC-1 activity (Creus pression (Marineli, Moura, etin mitochondrial al., activity 2015), pattern, fatty signalingsis acid control, improvement oxidation, and adipogene- prevention ofmediators the (Creus overexpression et of al., inflammatory 2016;& da Chang, Silva 2004). et al., 2018; Musch, Kapil, ance as a response toMoura, consumption et of al., chia 2015) seed (Figure and 2). oil (Marineli, the cellular energydeprivation. balance Its decrease and leadsergy to it metabolism, noticeable among works effects which on are ascose animal the and oxidative sensor en- pathways lipids of (Nelson of glu- & Cox,that energy- 2014). diets It high is already in wellholm fat established et and al., 2013; sucrose Yang, (or Miyahara,HSP Takeo, both) & expression Katayama, reduce (Chung 2012) AMPK et and al., (Lind- compounds 2008). present a Therefore, promising chia role seed inanimals and energetic fed metabolism its unbalanced since diets, when fedrylation chia, had restored AMPK phospho- as controlother animals. markers, Besides including carnitine that, palmitoyltransferase chia(Creus 1 et modulates (CTP-1) al., 2017; Fortinoactivated et receptor- al., 2017), peroxisome proliferator- rats fed with aninsulin unbalanced sensitivity diet (Chicco improved et glucoseet al., tolerance al., 2009; and Creus 2017; et2016; Ferreira, al., Fonte-Faria 2016; Alvarez, et Creus Illesca,Moura, al., et Gim al., 2019; 2015; Marineli, Fortino2013; Lenquiste, Poudyal, et et Panchal, Waanders, al., et al., 2015; al.,Ward, Oliva 2012; 2017; et et Poudyal, al., Panchal, Marineli, al.,firmed 2012; Rui by additional etexpression data al., of of 2018). chia heat Thesesoleus seed shock effects muscle intake, (Marineli, were proteins such Moura, con- stimulated as 25 et increased phosphorylation (HSP25) al., on 2015), andtion increased on IRS-1 HSP70 insulin- gastrocnemius and (Fonte-Faria in etet GLUT-4 al., al., 2019) transloca- 2017), and increased hearttein adenosine (Creus kinase(AMPK) monophosphate-activated pro- phosphorylationFaria et on al., 2019), gastrocnemius cardiac musclesand (Fonte- (Creus subcutaneous et al., adipose 2017), tissues epididymal, (Rui et al., 2018). 232 3.2 Impact of chia on metabolic and associated disorders profile (Nieman et al., 2009;2014; Nieman Toscano et et al., al., 2012;(Toscano 2015; et Toscano et Vuksan al., al., et 2014; al.,blood Vuksan 2017), pressure et oxidative (Toscano al., stress et 2007;weight al., Vuksan loss et 2014; (Toscano al., et Vuksanthese 2017), parameters et al., were al., not 2015; reproducible. 2007),may This Vuksan lack be and et of due major al., to results can feasible 2017), be doses considered but of low when all chia compared(20 used to g/kg doses in body offered these to weight) studies, animals seed (Creus which (as et food) al., expected 2017).too to The high improve amount for metabolic human of parameters consumption. chia may be Chia seed effects on unbalanced diet . . .

Concise Reviews & Hypotheses in Food Science ee mrvmn Cese l,21;Cese l,21;Ferreira 2017; al., et Creus lipid 2016; plasmatic al., and et (Creus produc- decrease improvement ROS level glycemia and simultaneously peroxidation found its tion al. or et glucose lipids, evaluated Miranda that plasma review de this metabolism, of in included exception studies the the all (Marineli, With (2019), levels 2015). plasmatic al., its oxida- on et reduction lipoprotein Lenquiste, a low-density to of due probably decrease tion, the with that associated chia of lipid is effect plasma hypoglycemic to the connected of be decrease may The peroxidation 2015). al., 2016; reactive et al., decreasing Lenquiste, et Marineli, (Ferreira and peroxidation lipid 2015), and (ROS) al., species al., oxygen et et Lenquiste, Moura, Marineli, Marineli, 2018; 2015; al., restoring et capacity, Silva antioxidant (da enzymes total antioxidant increasing by stress oxidative for mation. triggers reverse may seed chia by normal- lipogenesis. response recovering the insulin events Thus, lipogenesis, of utilization. important ization on fuel most improvement balancing the and seed of beta-oxidation normal- chia one the is in that response involved is insulin hypothesis in- of Our and ization membrane. 2018) 2016) plasmatic al., al., et the (Creus et FAT/CD36 to of Rui translocation 2012; the induced al., sulin et Ward, Panchal, Poudyal, sub receptor insulin IRS1, peroxidase; dismutase. CTA, superoxide gluthatione kinase; SOD, GPx, protein species; phosphate; AMP-activated oxygen 6 AMPK, reactive glucose studies. G6PD, experimental I; diet PGC1- transferase unbalanced 1; on palmitoyl based carnitine action CTP-1, of acid; mechanism tricarboxylic seeds chia’s of 2–Hypothesis Figure . . . diet unbalanced on effects seed Chia .. mato hao xdtv tesadinflam- and stress oxidative on chia of Impact 3.2.3 α eoioepoieao-ciae eetrgmacatvtr1apa PPAR- 1-alpha; coactivator gamma receptor proliferator-activated peroxisome , eea uhr ecie hasefcso decreasing on effects chia’s described authors Several e hwdrdcino namto imres(ru tal., et (Creus biomarkers inflammation on reduction showed ies locations 2017). different al., from et chia Silva be (da of may conditions composition studies cultivation and distinct the between the observed to compounds variability due lipophilic The the oil. the in chia between components in activity chemical synergistic the and between may seed, interactions fractions both to al., for due et demonstrated be Lenquiste, effect (Marineli, beneficial al., stress The oil oxidative et 2015). and of seed (Oliveira-Alves modulation both different of the effects in are similar highlighted oil have studies and 2017), Oliveira-Alves seeds quantities 2010; chia compound al., phenolic between and Valdivia-L et activity & Ixtaina antioxidant Tecante, Although Reyes-Caudillo, 2017; 2017; ef- al., al., antioxidant et et with Silva associated (da were fects ALA), and tocopherols, phospholipids, and (carotenoids, compounds myricetin, lipophilic quercetin, and acid, kaempferol) chlorogenic danshensu, acid, feic 2015; al., peroxida- et 2015). Moura, al., in Marineli, et decrease Lenquiste, 2016; showed Poudyal al., Marineli, et papers 2012; (Ferreira other al., markers Oliva Three tion et 2017; 2013). Waanders, al., Panchal, et al., Poudyal, Fortino et 2019; 2013; al., al., et et Fonte-Faria 2016; al., et eadn h feto hase niflmain oestud- some inflammation, on seed chia of effect the Regarding caf- acid, (rosmarinic acids phenolic as such chia, in Compounds γ eoioepoieao-ciae eetrgma ROS, gamma; receptor proliferator-activated peroxisome , o.8,Is ,2020 2, Iss. 85, Vol. r ora fFo Science Food of Journal pz 2008). opez, ´ strate 233

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Concise Reviews & Hypotheses in Food Science ui ciiynraiainadpstv fet fci edon seed chia of effects in- positive about and health. hypothesis normalization previous activity con- our improve- lipogenesis sulin strengthens and other finding tolerance with This insulin and trol. associated glucose were as such interestingly 2018). ments, inflamma- Amaya-Farfan, them & of of Morato, overexpression All Lollo, which the (Moura, upregulation, mediators preventing HSP72 tory Pan- with and (Poudyal, 2012), associated fibrolisis al., is liver et al., 20132012), Waanders, et Ward, al., chal, Panchal, Poudyal, et Poudyal, Poudyal 2015; 2012; 2012; al., al., et et Waanders, Moura, Panchal, or ala- (Marineli, transaminase, 2012) aminotransferase glutamic-oxalacetic al., as Panchal, nine et Poudyal, such Ward, 2018; ones, Panchal, associated al., Poudyal, on et 2012; Silva al., da et 2017; Waanders, al., et Creus 2016; . . . diet unbalanced on effects seed Chia . mato hasbociecmonso metabolic on compounds bioactive chia’s of Impact 3.3 eadn hase,i shr oln h feto eaoimto metabolism on effect the link to hard Nevertheless, is 2017). Sadeghi, it seed, 2012; Meshkani, chia Ghosh, & regarding di- a & Golestani, Pal unbalanced play Ebrahimi, 2012; by others Seyyed al., triggered and et conditions (Gonzalez-Manan ALA), health ets example, acid), repairing (for rosmarinic in acid role and fatty acid, fiber, example, caffeic bioactive action. dietary (for acid, isolated specific compounds chlorogenic or a phenolic quercetin, sources for that food responsible evidenced other as compounds using compound studies able a are Previous out them of point none disorders However, to metabolic diets. improving unbalanced in by potential developed as seed chia of pounds l tde nlddi hsrve etoe h iatv com- bioactive the mentioned review this in included studies All n soitddisorders associated and o.8,Is ,2020 2, Iss. 85, Vol. uget bu ahrs fba tmfreach for study. item included bias of risk each about authors’ judgments review summary: bias of 3–Risk Figure r ora fFo Science Food of Journal 235

Concise Reviews & Hypotheses in Food Science ıvel ´ ıcius P. ´ ´ arbara P.Silva ` a Pesquisa do Estado de ¸oamento de Pessoal de N ´ ogico (CNPq) for the financial ˜ ao de Amparo ¸ ´ ercia S.D. Martino reviewed critically the ˜ ao de Aperfeic ¸ ıfico e Tecnol ´ ´ arbara N. Enes researched prior studies, evaluated each study, ˆ ancio drafted and reviewed critically the manuscript. Su- Wethank Coordenac The authors state they have no conflict of interest. B This review supports the prospective use of chia in the preven- Moreover, about the risk of bias (Figure 3), none of the studies ´ ucio researched prior studies and compiled data. Vin tion and treatment ofdiets. comorbidities Despite associated the withmans, limitations unbalanced in we extrapolating considerrealistic the chia consumption results seed of to chia avent hu- seeds potential and and attenuate bioactive oil metabolic food,data could about changes. be as which able We compound the highlight would todownregulate be the pre- the responsible to pathways lack stimulate discussed of or indose this that review would as present wellhealth. an as We efficient the reinforce and the secure needsider effect of the on future dose clinical human ofthat studies chia best impacts that seed health. con- Thus, consumed the dailyits biological effects and components of the the can seed seed and bedietary fraction clinically strategy to confirmed prevent and anduse treat may of chronic health represent tools problems. a for The that quality assessment suggest identified operational methodological improvementsresearch gaps on for running future high-quality experimental controlled trials. compiled data, interpreted the results,Luiza and P. drafted D. Moreira the researched manuscript. priorinterpreted studies, the evaluated results, each and study, drafted thecompiled manuscript. B data anddrafted drafted the the manuscriptL manuscript. and reviewed Mariana theVen Grancieri manuscript. Haira G. sanne U. Mertens-Talcott andcally the Carla manuscript. O.B. H Rosamanuscript and reviewed approved criti- the final andhave read revised version. and All approved authors the final manuscript. regarding experimental and statisticsregarding methods animals applied and in in publications. research reported about blinding the investigatorsOnly involved in one the study research. (daanimal’s Silva randomization to et groups. al., Sixteeninformation 2018) studies reported failed about details to allocation about report of the concealment information reported strategies.comings in The on studies designing lack may animalthe reveal studies, scientific significant which short- community instudies, turn to generating may obtain a impair reliable negativedata effect data about on from lack laboratorystrating previous research. of little Our blinding blinding in areLanfear, & experimental consent Jennions, research with 2015). (Holman,be Selection findings Head, solved and with demon- randomization measurement and bias(Macleod blinded can et assessment of al., outcome 2015),of since outcomes. We they suggest are researchersfollow involved related in the to animal ARRIVE studies the guidelines to reports. randomness to avoid misinformation in their ACKNOWLEDGMENTS CONFLICT OF INTEREST AUTHOR CONTRIBUTION 4. CONCLUSIONS Superior (CAPES), Fundac support. Minas Gerais (FAPEMIG),volvimento and Cient Conselho Nacional de Desen- , CTP-1, and CTP- α α -Tocotrienol, β , reducing the lipogenesis, α -Tocopherol, δ Vol. 85, Iss. 2, 2020 r -Tocopherol, γ + β ) related to lipogenesis and mitochondrial activity. α -Tocotrienol compared with nonroasted seeds, regardless of Journal of Food Science γ Based on the few studies that evaluated the effects of chia on Therefore, it still remains unclear if there is a specific bioactive Among the 17 studies evaluated, one study did not show the The fractions of the seed have different components that result -Tocopherol, ¨ Ozcan, Al-Juhaimi, Ahmed, Osman, & Gassem, 2019b). ¨ metabolic pathways, wecrease hypothesized AMPK that expression, which chia increases the compounds PGC1- in- and PGC1- 1, increasing the expressionincreasing of mitochondrial PPAR activity, and consequentlyidation. fatty Therefore, acid the ox- AMPKtranslocation together of with GLUT-4 IRS to stimulatesentrance plasmatic the of membrane glucose and inside allowsAMPK the allows the the cells, translocation reducing ofin the FAT/CD36 to IR. muscle the Moreover, sarcolemma cells,Chia’s effects facilitating on restoring the antioxidant FA defenseimprovement may on oxidation come glucose from by tolerance, the from mitochondria.tive stress, the or reduction the of improvement on oxida- it mitochondrial is dysfunction, unknown but how chiaenzymes seed (Figure is 2). able to increase these antioxidative compound or the synergism ofment them of is biomarkers implicated evidenced in by the thea improve- studies. direct None association of with them make atained. certain However, compound most with of theaction the results of ob- studies chia mentionedof on that glucose health the uptake, conditions major itsinsulin, is oxidation and due and its to restored regulation tissue the of sensibility improvement gene to expression (PPAR and the method used to obtain theRecent oil: data cold showed press that or heat Soxhlet acts extraction. and negatively bioactive on properties of physical-chemical chia oil, whereand the content phenolic of fatty compounds acids ( was decreased by microwave roasting dose of chiaNone administered to of the themand/or animals compounds discussed used (Chicco in potential et theinformation adverse intervention, al., as on effects well 2009). the as limitations insufficient of ofextrapolation the of the data study, especially doses to concerning humans2017; (Creus Oliva et et al., al., 2017; 2013; FortinoPoudyal, Poudyal, Panchal, et Panchal, Ward, et Waanders, al., al., et 2012; al., Poudyal et 2012; Sierra al., 2013) et (Table 2; al., 2015).(2009), Our findings who are claim consistent that to there Kilkenny et is al. a lack of important information 236 3.4 Reporting quality and risk of bias in distinct actions. Apparentlyas hydrolyzed extracts extracts from of the chia(Oliveira-Alves seed as et al., and well 2017), its and fiber flavonoidimpaired bioaccessibility present by may higher be the antioxidants seed’sstudies fat conducted with (Pellegrini chia et oilmation presented al., improvement in (Poudyal, 2018). inflam- Panchal, Nevertheless, Waanders,the et antioxidant system al., (Marineli, 2012) Lenquiste,that et compared and al., chia’s restored 2015). fraction Studies chia during oil different presents times aet showed faster that al., action than 2015; chiaies Marineli, seed must Lenquiste, (Marineli, be conducted et Moura, be to al., superior confirm 2015), it. to but Althoughserved the chia more in seed, oil order stud- to the seemsOzcan, avoid to extraction Al-Juhaimi, losses Ahmed, methods regarding Osman, antioxidant should and compounds. that Gassem be chia (2019a) oil showed ob- obtained fromα roasted seeds presents lower content of one specific compound. Evenoil the or studies fiber that cannot usedthat discern action. fractions which like “compound” is associated with Chia seed effects on unbalanced diet . . .

Concise Reviews & Hypotheses in Food Science IS1Tr/R- hshrlto nTr8 fIRS-1 of Tyr989 on phosphorylation pIRS-1(Tyr)/IRS-1 NOMENCLATURE . . . diet unbalanced on effects seed Chia OAI oesai oe seset insulin assessment: model homeostasis HOMA-IR A/C6ftyai translocase acid fatty FAT/DC36 C-o ogcanacyl-CoA long-chain LCA-CoA RIEaia eerhrprigo nvv exper- vivo in of reporting research animal ARRIVE RSApeerdrprigiesfrsseai re- systematic for items reporting preferred PRISMA LT4guoetasotrtp 4 type transporter glucose GLUT-4 PPAR- PPAR- PGC-1 AP hshrlto faeoiemonoph- adenosine of phosphorylation pAMPK IASLtnAeia n aiba etron Center Caribbean and American Latin LILACS NF- P- antn-amty transferase-1 carnitine-palmitoyl CPT-1 pro- monophosphate-activated adenosine AMPK S7 etsokpoen70 protein shock heat 60 protein shock HSP70 heat 25 protein shock HSP60 heat HSP25 -- glucose-6-phosphate G-6-P EAnnseie at acids fatty nonesterified NEFA RPfri euigaiiyo plasma of ability reducing ferric FRAP 6Dguoe6popaedehydrogenase glucose-6-phosphate G6PD Dchg-est iorti cholesterol lipoprotein high-density HDLc Daprvt eyrgns 1component E1 dehydrogenase pyruvate PDHa R- nui eetrsbtae1 substrate receptor insulin IRS-1 Dclwdniylipoprotein density low LDLc L1 nelui 10 interleukin IL-10 D att dehydrogenase lactate LDH C ctlCAcarboxylase acetyl-CoA ACC R -ecieprotein C-reactive CRP F ihftdiet high-fat HFD S eue glutathione reduced GSH A catalase CAT B isoi lo pressure blood diastolic DBP r2ncerfco eyhoddrvd2-ie2 2)-like (erythroid-derived factor nuclear Nrf2 L lh ioei acid linolenic alpha ALA I lcs nuinrate infusion glucose GIR S satt aminotransferase aspartate AST L lnn aminotransferase alanine ALT P lttin peroxidase glutathione GPx L laiephosphatase alkaline ALP L6itrekn6 interleukin IL-6 F reftyacid fatty free FFA A at cdsynthase acid fatty FAS Rguahoereductase glutathione GR Gdiacylglyceride DG Kcreatinine CK Taioetissue adipose AT κ 6oea6 omega 3 n6 omega n3 γ atrncerkpaB kappa nuclear factor B α α gamma receptor proliferator-activated peroxisome alpha receptor proliferator-activated peroxisome elhSine Information Sciences Health iw n meta-analysis and views γ receptor- proliferator-activated peroxisome alpha subunit kinase protein osphate-activated resistance iment kinase tein coactivator hn,J,Nue,A,Hntig,D . oms .G,Ca,M .S,Ms,J . . . . L., J. Mesa, S., Villafa A., H. Benmelej, M. A., Creus, Chan, G., A. Holmes, C., D. Henstridge, A., Nguyen, J., Chung, hco .G,DAesnr,M . en .J,Oia .E,&Lmad,Y .(09.Dietary (2009). B. Y. Lombardo, & E., M. Oliva, J., G. Hein, E., M. D’Alessandro, G., A. Chicco, hco .G,DAesnr,M . en .J,Oia .E,&Lmad,Y .(2008). B. Y. Lombardo, & E., M. Oliva, J., G. Hein, E., M. D’Alessandro, G., A. Chicco, Eval- (2013). Tom F., Blachier, C. T., Chalvon-demersay, Severin, & V., Flores, O., Sapio, Di M., Bueno, M., Quiroga, H., Busilacchi, oosa . Brz & chia S., lipids Borowska, from derived plasma acid fatty on alpha-linolenic effects dietary of oil Effect (2007). W. chia Coates, & and J., R. seed Ayerza, chia Ground (2005). W. Coates, & R., potential Ayerza, as profiles acid fatty and content oil content, Protein (2011). W. Coates, & R., Ayerza, cycle growing and composition, acid fatty content, oil and protein seed’s The (2009). R. Ayerza, L A., Arvola, (2018). Database. 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