Eicosapentaenoic acid reduces adipocyte hypertrophy and inflammation in diet-induced obese mice in an adiposity-independent manner.
BACKGROUND
Obesity is associated with an overexpansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation, and thrombosis. Research to develop nutritional interventions to prevent or treat obesity and its associated diseases is greatly needed. Previously, we demonstrated the ability of eicosapentaenoic acid (EPA) to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation in mice.


OBJECTIVE
The objective of the current study was to determine the mechanisms mediating the anti-inflammatory and antilipogenic actions of EPA.


METHODS
In a previous study, male C57BL/6J mice were fed a low-fat diet (10% of energy from fat), an HF diet (45% of energy from fat), or an HF diet supplemented with EPA (45% of energy from fat; 36 g/kg EPA; HF+EPA) for 11 wk or an HF diet for 6 wk and then switched to the HF+EPA diet for 5 wk. In this study, we used histology/immunohistochemistry, gene expression, and metabolomic analyses of white adipose tissue from these mice. In addition, cultured mouse 3T3-L1 adipocytes were treated with 100 μM EPA for 48 h and then used for extracellular flux assays with untreated 3T3-L1 adipocytes used as a control.


RESULTS
Compared with the HF diet, the HF+EPA diet significantly reduced body weight, adiposity, adipocyte size, and macrophage infiltration into adipose tissue. No significant differences in overall body weight or fat pad weights were observed between HF-fed mice vs. those fed the HF+EPA diet for a short time after first inducing obesity with the HF diet. Interestingly, both histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed the HF diet and then switched to the HF+EPA diet vs. those fed HF diets only. This indicated that EPA was able to prevent as well as reverse HF-diet-induced adipocyte inflammation and hypertrophy and that some of the metabolic effects of EPA were independent of body weight or adiposity. In addition, adipose tissue metabolomic data and cultured adipocyte extracellular flux bioenergetic assays indicated that EPA also regulated mitochondrial function by increasing fatty acid oxidation and oxygen consumption, respectively.


CONCLUSIONS
With the use of mice and cultured adipocytes, we showed that EPA ameliorates HF-diet effects at least in part by increasing oxygen consumption and fatty acid oxidation and reducing adipocyte size, adipogenesis, and adipose tissue inflammation, independent of obesity.
Department of Nutritional Sciences, College of Human Sciences and Obesity Research Cluster, Texas Tech University, Lubbock, TX; and.
Monique J
MJ
LeMieux
Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
Nishan S
NS
Kalupahana
Department of Nutritional Sciences, College of Human Sciences and Obesity Research Cluster, Texas Tech University, Lubbock, TX; and.
Shane
S
Scoggin
Department of Nutritional Sciences, College of Human Sciences and Obesity Research Cluster, Texas Tech University, Lubbock, TX; and naima.moustaid-moussa@ttu.edu.
Naima
N
Moustaid-Moussa
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects*; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D052436:Adipose Tissue, White; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006984:Hypertrophy / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism
D052242:Adiponectin; D004041:Dietary Fats; D017382:Reactive Oxygen Species; D015118:Eicosapentaenoic Acid
adipocyte; diet-induced obesity; eicosapentaenoic acid; inflammation; omega-3 fatty acids