Low Dietary n6/n3 Ratio Attenuates Changes in the NRF 2 Gene Expression, Lipid Peroxidation, and Inflammatory Markers Induced by Fructose Overconsumption in the Rat Abdominal Adipose Tissue

Abstract

The objective of this study was to examine the benefits of different n6/n3 polyunsaturated fatty acid ratios on the lipid metabolism, insulin resistance, and oxidative stress in the adipose tissue of rats fed a high-fructose diet. Male and female rats were divided into four groups: a control group (CON) (n6/n3 ratio ~7), a high-fructose group (HF) (n6/n3 ratio ~7), an N6-HF group (n6/n3 ratio ~50), and the DHA-HF group (n6/n3 ratio ~1, with the addition of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid). The CON group received plain water and the HF group received 15% fructose in their drinking water. Fructose induced an increase in the content of serum triglycerides, serum cholesterol, and HOMA-IR index. Among the fatty acids, elevated proportions of C18:1n9 and C16:1n7, as well as an increase in total monounsaturated fatty acid (MUFA), were found in the adipose tissue of the HF group. Fructose treatment also changed oxidative parameters, including a marked increase in the serum malondialdehyde (MDA) content. Meanwhile, DHA supplementation caused a significant decrease in the serum MDA concentration in comparison with the HF group. In addition, DHA/EPA supplementation attenuated oxidative stress by increasing NRF 2 gene expression. Fructose treatment also significantly decreased the adiponectin level, while DHA supplementation ameliorated it. The changes observed in this trial, including the decrease in the content of DHA and EPA, the decreased EPA/ARA ratio, and the increase in the expression of inflammatory genes, are characteristics of the low-grade inflammation caused by fructose treatment. These changes in the rat adipose tissue could be prevented by dietary intervention consisting of DHA supplementation and a low n6/n3 ratio.

Different ratios of DHA/EPA reverses insulin resistance by improving adipocyte dysfunction and lipid disorders in HFD-induced IR mice

“…Research from Roškarić et al indicated that DHA supplementation caused a significant decrease in the serum MDA concentration in comparison with the HF group. 37 Moreover, research in recent years have shown that different carbon chains and double bond numbers between DHA and EPA are the contributing factors to the different effects of DHA/EPA intervention in the anti-oxidation systems, although the underlying mechanism is still unclear. 38 In addition, a higher level of DHA in serum was negatively correlated with inflammation.…”

Pancreas–Liver–Adipose Axis: Target of Environmental Cadmium Exposure Linked to Metabolic Diseases

“…TNF-α, IL-6, and IL-1β signaling increase ROS production in the adipose tissue of obese individuals [ 37 , 237 ]. In cell cultures, 3T3-L1 adipocytes treated with TNF-α decreased the expression of antioxidants, such as GST, peroxiredoxin, and GPx, resulting in protein carbonylation, ROS generation, and mitochondrial dysfunction [ 238 , 239 ]. In adipocytes, ROS can be produced by NADPH oxidase (Nox), xanthine oxidases, and mitochondria.…”