Abstract

ScopesTo investigate the effects of high-fat diet enriched with lard oil or soybean oil on liver endoplasmic reticulum (ER) stress and inflammation markers in diet-induced obese (DIO) rats and estimate the influence of following low-fat diet feeding.Methods and ResultsMale SD rats were fed with standard low-fat diet (LF, n = 10) and two isoenergentic high-fat diets enriched with lard (HL, n = 45) or soybean oil (HS, n = 45) respectively for 10 weeks. Then DIO rats from HL and HS were fed either high-fat diet continuously (HL/HL, HS/HS) or switched to low-fat diet (HL/LF, HS/LF) for another 8 weeks. Rats in control group were maintained with low-fat diet. Body fat, serum insulin level, HOMA-IR and ectopic lipid deposition in liver were increased in HL/HL and HS/HS compared to control, but increased to a greater extent in HL/HL compared to HS/HS. Markers of ER stress including PERK and CHOP protein expression and phosphorylation of eIF2α were significantly elevated in HL/HL group while phosphorylation of IRE1α and GRP78 protein expression were suppressed in both HL/HL and HS/HS. Besides, inflammatory signals (OPN, TLR2, TLR4 and TNF-α) expressions significantly increased in HL/HL compared to others. Switching to low-fat diet reduced liver fat deposition, HOMA-IR, mRNA expression of TLR4, TNF-α, PERK in both HL/LF and HS/LF, but only decreased protein expression of OPN, PERK and CHOP in HL/LF group. In addition, HL/LF and HS/LF exhibited decreased phosphorylation of eIF2α and increased phosphorylation of IRE1α and GRP78 protein expression when compared with HL/HL and HS/HS respectively.ConclusionsLard oil was more deleterious in insulin resistance and hepatic steatosis via promoting ER stress and inflammation responses in DIO rats, which may be attributed to the enrichment of saturated fatty acid. Low-fat diet was confirmed to be useful in recovering from impaired insulin sensitivity and liver fat deposition in this study.

Highlights

  • Over the decades, there has been a rapid increase in the prevalence of obesity worldwide [1,2,3]

  • Lard oil was more deleterious in insulin resistance and hepatic steatosis via promoting endoplasmic reticulum (ER) stress and inflammation responses in diet-induced obese (DIO) rats, which may be attributed to the enrichment of saturated fatty acid

  • Effect of Different Fat Types on Hepatic ER Stress higher intra-abdominal fat, body fat percentage, serum insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) compared with LF group (P,0.05) as presented in table 2

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Summary

Introduction

There has been a rapid increase in the prevalence of obesity worldwide [1,2,3]. Obesity is a known risk factor of many metabolic disease including atherosclerotic cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) [4,5] These diseases constitute the greatest current threat to global public health. Toll like receptors (TLRs) were proposed to function as free fatty acid sensor which link insulin resistance and inflammation response and result in the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-a) and interleukin 6 (IL-6) [21,22]. Despite these findings, the precise mechanism underlying inflammation and obesity remains unknown

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