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Polyphenol‐Rich Extract of Syzygium cumini Leaf Reduces Non‐alcoholic Fatty Liver Disease in MSG‐obese Mice by a Joint Action on Insulin Resistance and Endoplasmic Reticulum Stress
Author(s) -
França Lucas Matins,
Santos Pâmela Costa,
Flister Karla Frida Torres,
Vale Caroline Castro,
Sanches Jonas Rodrigues,
Benevides Renata Ohana Alves,
Ribeiro Nathalee Liberal Xavier,
Laurindo Francisco Rafael Martins,
Andrade Paes Antonio Marcus
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.646.45
Subject(s) - endocrinology , medicine , fatty liver , insulin resistance , lipogenesis , unfolded protein response , white adipose tissue , endoplasmic reticulum , adipose tissue , lipid metabolism , chemistry , diet induced obese , insulin , biochemistry , disease
The hepatic endoplasmic reticulum stress (ER stress) sustains non‐alcoholic fatty liver disease (NAFLD) putting hepatic de novo lipogenesis into a vicious cycle. Early studies from our group have shown that polyphenol‐rich extract of S. cumini leaf (HESc) improves NAFLD in monosodium L‐glutamate (MSG)‐obese rats. Thus, this study aimed to investigate the effects of HESc on lipid metabolism and ER stress markers in the liver of MSG‐obese mice. MSG‐obese mice were orally treated with HESc (Obese+HESc, 0,5 g/kg/day) for 4 weeks, whereas other MSG‐Obese and Lean mice received saline. Weight gain, food intake, feed efficiency and Lee index (LI) were measured for obesity development assessment. At the end of treatment, glucose (GTT) and insulin (ITT) tolerance tests were performed. Blood, white adipose tissues (WAT) and liver were collected upon euthanasia of anesthetized animals. Serum glucose (GL), triglycerides (TG), total cholesterol (TC), free fatty acids (FFA) and insulin levels were determined and used to calculate HOMA‐IR and TyG indexes. WAT was weighed and their lipolytic activity assessed. Hepatic tissue was used to determine the lipid profile and gene expression of markers associated to TG synthesis (SREBP1c, PPARs, FAS, SCD1 and DGAT2) and exportation (APOB, PDI and MTTP). Expression of ER stress‐related genes (ATF6, IRE1α, PERK, NRF2 and CHOP) were also measured. HESc reduced the body weight (12%), LI (6%) and WAT (20%) as compared to Obese non‐treated mice. GL, TG, insulin and FFA levels were diminished in 38, 37, 29 and 30%, respectively. HESc improved insulin sensitivity by reducing both HOMA‐IR (56%) and TyG (9%) indexes, meanwhile increased k ITT (87%). Lipolytic activity of Obese+HESc was increased in both basal (72%) and isoproterenol‐stimulated (42%) conditions. Total fat liver and TG content were reduced in 29 and 22%, respectively. HESc decreased the expression of PPARγ (35%), SREBP1c (52%), PPARα (56%), FAS (63%), DGAT2 (50%), ApoB (50%), MTTP (45%), PERK (66%) and NRF2 (50%), as compared to Obese non‐treated mice. On the other hand, hepatic expression of IRE1α, ATF6, PDI and CHOP genes did not change among groups. Therefore, our data suggest that HESc amelliorates NAFLD in MSG‐obese mice by improving insulin sensitivity and downregulating gene expression of hepatic lipogenesis markers, as well as PERK downstream pathway, an important lipogenic inducer of ER stress in the liver. Support or Funding Information FAPEMA, UFMA and CAPES