Eicosapentaenoic Acid Increases Browning Markers in Subcutaneous Adipose Tissue and Primary Adipocytes from Wild Type and UCP‐1 Deficient Mice

Abstract Objectives Brown adipose tissue (BAT) regulates energy balance through thermogenesis, in part via uncoupling protein -1 (UCP-1). White adipose tissue (WAT), namely subcutaneous adipose tissue (SAT) can convert to a beige/brite adipose tissue phenotype (browning) under thermogenic conditions such as cold. We previously reported that eicosapentaenoic acid (EPA) reduced obesity and glucose intolerance, and increased UCP-1 in BAT of B6 mice at ambient temperature (22°C); and these effects were attenuated at thermoneutral environment (28–30°C). We hypothesized that EPA exerts anti-obesity effects on SAT, including increased browning, adipocyte hypotrophy; and these effects require UCP-1. Methods Six-week-old B6 wild type (WT) and UCP-1 knock-out (KO) male mice were maintained at thermoneutral environment and fed high fat diet (HF) with or without 36 g/kg of AlaskOmega EPA-enriched fish oil (800 mg/g) for 14 weeks; and SAT was collected for histological, gene and protein analyses. SAT was also prepared from chow diet-fed WT and KO mice at ambient environment to prepare stroma vascular cells, which were differentiated into adipocytes, treated with 100uM EPA for 48 hours then harvested for mRNA and protein analyses. Results KO mice fed HF diets had the highest body weight (P < 0.05) among all groups. EPA reduced fat cell size in both WT and KO mice fed the EPA diet. mRNA levels of fibroblast growth factor-21 (FGF-21) were higher in SAT of WT mice fed EPA compared to WT mice fed HF (P < 0.05), with no differences between the KO genotype. KO mice fed HF diets had lower levels of UCP-3 in SAT compared to WT mice fed HF (P < 0.05), which was rescued only in the KO mice fed EPA (P < 0.05). UCP-1 protein levels were very low in SAT tissues, and UCP-2 mRNA levels were similar across all groups in SAT. Interestingly, EPA significantly (P < 0.05) increased mRNA expression of UCP-2, UCP-3 and FGF21 in differentiated SAT adipocytes from both WT and KO compared to control. Furthermore, UCP-1 mRNA levels were significantly higher in WT adipocytes treated with EPA, compared to non-treated cells (P < 0.05). Additional mechanistic studies are currently underway to further dissect adipose depot differences in EPA effects in WT vs. KO mice. Conclusions Our data suggest that EPA increases SAT browning, independently of UCP-1. Funding Sources NIH/NCCIH.

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Divergent responses to thermogenic stimuli in BAT and subcutaneous adipose tissue from interleukin 18 and interleukin 18 receptor 1-deficient mice

Scientific Reports ◽

10.1038/srep17977 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 17

Author(s):

Patricia Pazos ◽

Luis Lima ◽

Sulay Tovar ◽

David González-Touceda ◽

Carlos Diéguez ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Interleukin 18 ◽

Subcutaneous Adipose ◽

Deficient Mice

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Temperature-Dependent Effects of Eicosapentaenoic Acid on Browning of Subcutaneous Adipose Tissue From UCP1 Knockout Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab055_072 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1262-1262

Author(s):

Yujiao Zu ◽

Mandana Pahlavani ◽

Latha Ramalingam ◽

Shane Scoggin ◽

Naima Moustaid-Moussa

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Glucose Tolerance ◽

Eicosapentaenoic Acid ◽

Ambient Temperature ◽

Subcutaneous Adipose Tissue ◽

Brown Fat ◽

Metabolic Effects ◽

Diet Induced Obesity ◽

Subcutaneous Adipose

Abstract Objectives Activation and recruitment of thermogenic cells in white adipose tissue (WAT browning), in response to cold exposure, can combat obesity and associated metabolic disorders. We have previously reported that the beneficial effects of eicosapentaenoic acid (EPA), a long-chain omega 3 polyunsaturated fatty acids, in obesity and insulin resistance are independent of UCP1. In this study, we investigate the protective effects of EPA and the role of UCP1 in the browning of subcutaneous adipose tissue (SAT) at ambient and thermoneutral environments using UCP1 knockout (KO) mice. We hypothesized that EPA promotes SAT browning to prevent diet-induced obesity at both temperatures, independently of UCP1. Methods Male and UCP1 KO and wild type (WT) B6 littermates were housed at room temperature (22°C) or thermoneutrality (28–30°C) and fed a high fat (HF) diet (45% kcal fat) supplemented with or without EPA (36g/kg) for 14 weeks. Body weight and glucose tolerance test (GTT) were measured, and browning-related markers were assessed in SAT. Data were statistically analyzed via three-way ANOVA using GraphPad to determine the individual and interactive effects of temperature, genotype, and diet. Results Compared to the WT, the body weight (BW) of KO mice increased at thermoneutrality (P < 0.01) but decreased at ambient temperature (P < 0.0001). Additionally, EPA attenuated weight and fat mass gain at thermoneutrality and improved glucose tolerance at both temperatures in both genotypes. mRNA levels for brown fat markers (Dio2 and Cidea), lipid metabolism (Elovl3, PGC1α, FASN, Cpt1b, and Gpd1), and batokines (Bmp8b and FGF21) were significantly up-regulated in KO mice, compared to WT, at ambient temperature (P < 0.01). Moreover, compared to HF-fed mice, EPA increased above markers in the KO mice at ambient temperature. Compared to HF, EPA-fed mice had significantly higher serum adiponectin levels (P < 0.01) in both genotypes and temperatures. Conclusions UCP1 KO male mice were protected from diet-induced obesity and glucose intolerance and had increased SAT browning at ambient temperature. These results indicate that alternative thermoregulatory pathways mediate protective metabolic effects of EPA, in the absence of UCP1. These findings may be translated to human subjects with obesity, who exhibit low amounts of brown fat and UCP1. Funding Sources NIH R15AT008879-01A1.

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