Docosahexaenoic Acid Counteracts the Hypoxic-Induced Inflammatory and Metabolic Alterations in 3T3-L1 Adipocytes

Abstract

Background: Hypoxia is caused by the excessive expansion of the white adipose tissue (AT) and is associated with obesity-related conditions such as insulin resistance, inflammation, and oxidative stress. Docosahexaenoic acid (DHA) is an omega-3 fatty acid reported to have beneficial health effects. However, the effects of DHA in AT against hypoxia-induced immune-metabolic perturbations in adipocytes exposed to low O2 tension are not well known. Consequently, this study aimed to evaluate the impact of DHA on markers of inflammation, metabolism, apoptosis, and oxidative stress in 3T3-L1 cell adipocytes exposed to low O2 tension (1% O2) induced hypoxia. Methods: The apoptosis and reactive oxygen species (ROS) rates were evaluated. Metabolic parameters such as lactate, FFA, glycerol release, glucose uptake, and ATP content were assessed by a fluorometer. The expression of HIF-1, GLUT1 and the secretion of adipocytokines such as leptin, adiponectin, and pro-inflammatory markers was evaluated. Results: DHA-treated hypoxic cells showed significantly decreased basal free fatty acid release, lactate production, and enhanced glucose consumption. In addition, DHA-treatment of hypoxic cells caused a significant reduction in the apoptosis rate and ROS production with decreased lipid peroxidation. Moreover, DHA-treatment of hypoxic cells caused a decreased secretion of pro-inflammatory markers (IL-6, MCP-1) and leptin and increased adiponectin secretion compared with hypoxic cells. Furthermore, DHA-treatment of hypoxic cells caused significant reductions in the expression of genes related to hypoxia (HIF-1, HIF-2), anaerobic metabolism (GLUT1 and Ldha), ATP production (ANT2), and fat metabolism (FASN and PPARY). Conclusion: This study suggests that DHA can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis.

Unlocking the potential of Rosa roxburghii Tratt polyphenol: a novel approach to treating acute lung injury from a perspective of the lung-gut axis

“…Intriguingly, after early intervention with RRTP, MDA and MPO decreased significantly, while SOD and GSH increased significantly. The RRTP-regulated lipid and amino acid differential metabolites, including docosahexaenoic acid ( Tatsumi et al, 2022 ; Younes et al, 2022 ), docosapentaenoic acid ( Wang et al, 2019 ) and histidine ( Thalacker-Mercer and Gheller, 2020 ), identified in our metabolomics study, have effects on reducing inflammation and alleviating oxidative stress. Furthermore, Bacteroidota is one of the most aerobically tolerant anaerobic bacteria, and its relative abundance increases significantly under ascending levels of oxidative stress in the organism ( Zafar and Saier, 2021 ).…”

Dysbiosis of oral and gut microbiota and its association with metabolites in patients with different degrees of coronary artery stenosis

“…[ 4 ] Docosahexaenoic acid (DHA) can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis. [ 5 ] N-arachidonoyl dopamine (N-ADA) possesses anti-inflammatory properties. [ 6 ] Our results showed that, compared to the control group, the MMCS and MSCS groups had higher levels of IL-6 and 3-HA and lower levels of N-ADA.…”