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

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.

scholarly journals Eicosapentaenoic Acid Increases Browning Markers in Subcutaneous Adipose Tissue and Primary Adipocytes from Wild Type and UCP-1 Deficient Mice (P15-007-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shasika Jayarathne ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
Naima Moustaid-Moussa
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
Subcutaneous Adipose Tissue ◽  
Uncoupling Protein ◽  
Fibroblast Growth Factor 21 ◽  
Chow Diet ◽  
Mrna Levels ◽  
Wild Type ◽  
Brown Adipose ◽  
Subcutaneous Adipose

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.

scholarly journals Subcutaneous adipose tissue accumulation protects systemic glucose tolerance and muscle metabolism

Adipocyte ◽  
2018 ◽  
Vol 7 (4) ◽  
pp. 261-272 ◽  
Author(s):  
A.D. Booth ◽  
A.M. Magnuson ◽  
J. Fouts ◽  
Y. Wei ◽  
D. Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Subcutaneous Adipose Tissue ◽  
Muscle Metabolism ◽  
Tissue Accumulation ◽  
Subcutaneous Adipose

scholarly journals Thermoneutrality Reduces the Beneficial Metabolic Effects of Eicosapentaenoic Acid on White Adipose Tissue in Diet-Induced Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1254-1254
Author(s):  
Bimba Goonapienuwala ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Kembra Albracht-Schulte ◽  
William Festuccia ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Eicosapentaenoic Acid ◽  
Uncoupling Protein ◽  
Serum Triglyceride ◽  
Metabolic Effects ◽  
Omega 3 ◽  
Adipocyte Size ◽  
Mitochondrial Energy Metabolism ◽  
Significant Difference

Abstract Objectives At ambient temperature (23°C), eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid reduces visceral adipose tissue (VAT) inflammation, adipocyte size and improves overall metabolic profile in diet-induced obese (DIO) mice, potentially through upregulation of uncoupling protein 1 (UCP-1). The goal of this study is to determine whether effects of EPA are maintained at thermoneutrality, and/or mediated by UCP-1, and if so through which cellular mechanisms. Methods Wild type (WT) and UCP-1 knockout (KO) B6 male mice were housed at thermoneutral temperature (28–30°C) and fed high fat (HF, 45% kcal fat) supplemented with or without EPA (36 g/kg diet). Serum, VAT (epididymal fat) and cecal microbiome specimens were analyzed. Results EPA reduced adiposity and improved glucose tolerance in EPA-fed KO mice (P &lt; 0.05), but not in EPA-fed WT mice. EPA supplementation lowered VAT mass in both genotypes (P &lt; 0.05); however, there were no diet or genotype-related differences in adipocyte size or serum triglyceride levels. Both genotypes fed EPA had lower serum resistin levels compared to respective HF (P &lt; 0.01). EPA showed trends towards increased serum adiponectin levels compared to HF fed mice in both genotypes, with KO-EPA group having the highest concentration. There was no significant difference in the expression of IL-6 in VAT among the groups, while MCP-1 mRNA was expressed more in KO groups compared to WT groups (P &lt; 0.01). Diet had no effect on expression of anti-inflammatory markers in both WT and KO mice. There were no genotype or diet effects on expression of genes involved in lipid metabolism and mitochondrial energy metabolism. Cecal microbiome showed no differences in the species diversity (Shannon index) between genotypes or diet types. However, only in the KO group, the Bacteroidetes/Firmicutes ratio was increased by EPA. Conclusions Compared to previous work at ambient temperatures, VAT does not mediate protective effects of EPA in DIO mice at thermoneutral temperature. Moreover, EPA effects are independent of UCP-1 as it produced beneficial effects on glucose tolerance and adiposity in KO mice, which may be in part mediated by changes in microbiome. Further mechanistic studies are ongoing to understand the mechanisms mediating EPA and UCP-1 effects in VAT. Funding Sources Funded by NIH (NCCIH and NIA).

scholarly journals Deficiency of lymphotoxin-α does not exacerbate high-fat diet-induced obesity but does enhance inflammation in mice

2012 ◽  
Vol 302 (8) ◽  
pp. E961-E971 ◽  
Author(s):  
Nathalie Pamir ◽  
Timothy S. McMillen ◽  
Kimberly A. Edgel ◽  
Francis Kim ◽  
Renée C. LeBoeuf
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Tissue Level ◽  
Specific Gene ◽  
High Fat ◽  
Tissue Macrophage ◽  
Diet Induced Obesity ◽  
Inflammatory Status ◽  
Lymphotoxin Α

Lymphotoxin-α (LTα) is secreted by lymphocytes and acts through tumor necrosis factor-α receptors and the LTβ receptor. Our goals were to determine whether LT has a role in obesity and investigate whether LT contributes to the link between obesity and adipose tissue lymphocyte accumulation. LT deficient (LT−/−) and wild-type (WT) mice were fed standard pelleted rodent chow or a high-fat/high-sucrose diet (HFHS) for 13 wk. Body weight, body composition, and food intake were measured. Glucose tolerance was assessed. Systemic and adipose tissue inflammatory statuses were evaluated by quantifying plasma adipokine levels and tissue macrophage and T cell-specific gene expression in abdominal fat. LT−/− mice were smaller (20%) and leaner (25%) than WT controls after 13 wk of HFHS diet feeding. LT−/− mice showed improved glucose tolerance, suggesting that, in WT mice, LT may impair glucose metabolism. Surprisingly, adipose tissue from rodent chow- and HFHS-fed LT−/− mice exhibited increased T lymphocyte and macrophage infiltration compared with WT mice. Despite the fact that LT−/− mice exhibited an enhanced inflammatory status at the systemic and tissue level even when fed rodent chow, they were protected from enhanced diet-induced obesity and insulin resistance. Thus, LT contributes to body weight and adiposity and is required to modulate the accumulation of immune cells in adipose tissue.

Monocyte-associated chemokine expression in cells from subcutaneous adipose tissue isolated from operation material in patients during abdominoplasty

2017 ◽  
pp. 70-78
Author(s):  
А.Е. Копасов ◽  
С.Н. Блохин ◽  
С.Г. Морозов
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Aesthetic Surgery ◽  
Normal Body ◽  
Chemokine Expression ◽  
Normal Body Weight ◽  
Functional Features ◽  
Subcutaneous Adipose ◽  
The Relationship

Цель работы - изучение взаимосвязи между уровнем хемокинов и интенсивностью воспалительного процесса в подкожно-жировой ткани (ПЖТ) у лиц с ожирением и нормальной массой тела. Задача работы - определение уровня экспрессии хемокинов, сопряженных с моноцитами/макрофагами, и их рецепторов в клетках ПЖТ, выделенных при проведении абдоминопластики. Пациенты. В период с 2013 по 2017 гг. в Клинике пластической и эстетической хирургии проведены операции абдоминопластики у 262 женщин, биологический материал которых использован в работе. Методы. Состав тела и процент жировой массы определяли методом биоимпедансного анализа. Из образцов ПЖТ из операционного материала выделяли клетки, окрашивали их меченными флуоресцеинами антителами к хемокинам и анализировали на проточном цитометре FACSCalibur по программе SimulSet. Статистический анализ проводили по программе ANOVA. Результаты. Показано, что наличие ожирения оказывает влияние на клеточный состав ПЖТ. Экспрессия хемокинов семейства CC, а также рецепторов хемокинов CCR1, CCR2 и CCR5 в ПЖТ у пациентов с ожирением достоверно выше, чем у пациентов с нормальной массой тела. Заключение. Различия в экспрессии хемокинов на клетках ПЖТ у пациентов с ожирением или с нормальной массой тела отражают функциональные особенности ПЖТ и могут оказывать влияние на развитие осложнений после проведения операции абдоминопластики. AIM: we study the relationship between chemokines and intensity of the inflammatory process in the subcutaneous adipose tissue (SAT) in individuals with obesity and normal body weight. Objective: we determined the expression levels of chemokines associated with monocyte/macrophages, as well as their receptors on the cells of SAT, that were obtained during abdominoplasty. Patients. In this work we have used the biological material of 262 women to whom has been performed an abdominoplasty in the Clinic of plastic and aesthetic surgery from 2013 to 2017 years. Methods. Body composition and the weight of body fat were determined by bioimpedance analysis. SATs have been obtained during abdominoplasty surgery. SAT cells were isolated followed by the staining with fluoresceine labeled antibodies which fluorescence was analyzed using a flow cytometer FACSCalibur according to the program SimulSet. Statistical analysis was carried out using ANOVA. Results. It has been shown that the progressing obesity may affect the SAT cellular composition. The expression of chemokines from CC family and its receptors (CCR1, CCR2 and CCR5) on cells from SAT were significantly higher in patients with obesity compared to the normal body weight patients. Conclusions. Differences in the chemokine expression on SAT cells between patients with obesity and with normal body weight may reflect the functional features of SAT itself and can modify the complication developments after abdominoplasty.

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