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High‐sucrose Diet Time‐dependently Changes Hepatic Endoplasmic Reticulum Stress from an Adaptive to Pro‐apoptotic Pattern in Young Mice
Author(s) -
Andrade Paes Antonio Marcus,
Flister Karla Frida Torres,
Santos Pâmela Costa,
Pinto Bruno Araújo Serra,
Vale Caroline Castro,
Kajihara Daniela,
Laurindo Francisco Rafael Martins,
França Lucas Martins
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.31.4
Subject(s) - medicine , endocrinology , endoplasmic reticulum , unfolded protein response , adipose tissue , white adipose tissue , insulin , chemistry , atf6 , chop , fatty liver , biology , biochemistry , disease
The relationship between excessive nutrient intake and hepatic endoplasmic reticulum stress (ER stress) is well stablished. However, mechanisms underlying the progression from adaptive to apoptotic pattern are still unclear. This study sought to investigate the effects of high‐sucrose diet on metabolic disorders associated to hepatic ER stress. Weaned Swiss mice received standard chow (CTR) or high‐sucrose diet (HSD; 25% sucrose) for distinct periods of 30 (CTR 30 and HSD 30 ) and 60 (CTR 60 and HSD 60 ) days. Weight gain, food intake, feed efficiency and Lee index (LI) were measured for obesity development assessment. At each treatment end, glucose (GTT) and insulin (ITT) tolerance tests were performed. Blood, white adipose tissue (WAT) depots and liver were collected upon euthanasia of anesthetized animals. Serum glucose (GL), triglycerides (TG), total cholesterol (TC) and free fatty acids (FFA) levels were determined. WAT depots were weighed and their lipolytic activity assessed. Hepatic tissue was used to determine the lipid profile and gene expression of ER stress (ATF6, IRE1α, PERK, GRP78, PDI, NRF2) and pro‐apoptotic (CHOP and caspase 2) markers. Only HSD 60 showed higher weight gain (8%), LI (3%) and feed efficiency (31%), as compared to CTR 60 . WAT was 2‐fold higher in HSD 60 than in HSD 30 , whereas both of them were significantly higher than their controls. Lipolytic activity under isoproterenol‐stimulation was 40% lower in HSD 60 . Serum GL and TC were increased in 20 and 40%, respectively, in both HSD groups. However, TG (43%) and FFA (25%) were increased only in HSD 60 . Area under the curve of GTT was augmented in both HSD 30 (14%) and HSD 60 (41%), as compared to their controls. Whereas only HSD 60 presented reduced k ITT (37%) and increase TyG (8%). Total fat liver content was increased in 22 and 61% for HSD 30 and HSD 60 , respectively. On the other hand, hepatic TG was augmented only in HSD 60 (69%). HSD 30 presented increased hepatic gene expression of GRP78 (57%), PERK (83%), IRE1α (49%), ATF6 (70%), PDI (41%) and NRF2 (32%), and reduced expression of CHOP (39%). An opposite pattern was found in HSD 60 , with reduced expression of PERK (34%), IRE1α (52%), ATF6 (36%) and PDI (46%), and increase expression of CHOP (72%). Notwithstanding, caspase‐2 expression did not change in any group. Therefore, our data suggest the HSD intake for up to 60 days after weaning rapidly promotes metabolic disorders associate to early onset of hepatic ER stress, which promptly progress from an adaptive to a pro‐apoptotic pattern. Support or Funding Information FAPEMA, CNPq, CAPES and UFMA.