Partial Replacement of Dietary Fat with Polyunsaturated Fatty Acids Attenuates the Lipopolysaccharide-Induced Hepatic Inflammation in Sprague-Dawley Rats Fed a High-Fat Diet

Abstract

In this study, we investigated whether the partial replacement of dietary fat with polyunsaturated fatty acids (PUFAs) ameliorated the lipopolysaccharide (LPS)-induced hepatic inflammation in rats fed a high-fat diet. Male Sprague-Dawley rats were divided into three groups and provided each of the following diets: (1) high-fat diet (HFD), (2) HFD with perilla oil (PO), and (3) HFD with corn oil (CO). After 12 weeks of dietary intervention, the rats were intraperitoneally injected with LPS (5 mg/kg) from Escherichia coli O55:B5 or phosphate-buffered saline (PBS). Following LPS stimulation, serum insulin levels were increased, while PO and CO lowered the serum levels of glucose and insulin. In the liver, LPS increased the triglyceride levels, while PO and CO alleviated the LPS-induced hepatic triglyceride accumulation. In the LPS injected rats, the mRNA expression of genes related to inflammation and endoplasmic reticulum (ER) stress was attenuated by PO and CO in the liver. Furthermore, hepatic levels of proteins involved in the nuclear factor kappa-light-chain-enhancer of activated B cells/mitogen-activated protein kinase pathways, antioxidant response, and ER stress were lowered by PO- and CO-replacement. Therefore, the partial replacement of dietary fat with PUFAs alleviates LPS-induced hepatic inflammation during HFD consumption, which may decrease metabolic abnormalities.

Lowering n-6/n-3 Ratio as an Important Dietary Intervention to Prevent LPS-Inducible Dyslipidemia and Hepatic Abnormalities in ob/ob Mice

“…These results may imply that a lower ratio of n -6/ n -3 PUFAs inhibits hepatic TG accumulation and inflammation; therefore, we postulate that PO may mitigate hepatic function abnormalities in LPS-injected ob/ob mice. These results were observed in other mouse LPS models in our previous study [ 33 , 34 , 38 ]. To study how pathological remodeling affects liver tissue function, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels were measured.…”

“…Other pathological stimuli for atherosclerosis may include hypertension, chronic kidney disease, aging, hyperglycemia, and inflammatory responses. Previously, we reported that the LPS injection induced hyperlipidemia accompanied by increased TG, TC, HDL-C, and non-HDL-C levels and CVD expectancy in experimental rodents [ 33 , 38 ]. The administration of LPS can lead to rapid and transitory increases in pro-inflammatory cytokines such as TNF-α and IL-6 in mammals [ 52 ].…”

Partial Replacement of Dietary Fat with Krill Oil or Coconut Oil Alleviates Dyslipidemia by Partly Modulating Lipid Metabolism in Lipopolysaccharide-Injected Rats on a High-Fat Diet

“…The fatty acid composition of the experimental diets was determined by methyl esterification of boron trifluoride (BF 3 )-methanol [ 48 ]. Briefly, 0.1 g of sample was placed in a test tube, followed by the addition of 0.5 mL of heptadecanoic acid (C17:0; 1 mg/mL hexane).…”

“…Lipids were extracted from the liver using the method of Bligh and Dyer [ 54 ] with slight modifications [ 48 ]. Briefly, 0.1 g of tissue was added to a chloroform/methanol (1:2, v / v ) solution and centrifuged at 1800× g for 5 min to obtain the lower lipid layer containing TG and TC for analysis.…”

“…Thus, several studies have investigated the anti-inflammatory effects of natural products, compounds, or drugs using LPS-induced animals as models of acute inflammation [ 44 , 45 , 46 , 47 ]. Recently, we reported that the partial replacement of SFAs in a high-fat diet (HFD) with PUFAs such as perilla oil (PO) or corn oil at a converted dose (2–8%) suppressed insulin resistance and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) signaling pathways, and enhanced antioxidant enzyme expression in rats [ 48 ]. Intriguingly, we observed that PO and corn oil exacerbated dyslipidemia by elevating triglyceride (TG), total cholesterol (TC), non-high-density lipoprotein-cholesterol (non-HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels when injected with LPS.…”