Eicosapentaenoic acid (EPA) vs. Docosahexaenoic acid (DHA): Effects in epididymal white adipose tissue of mice fed a high-fructose diet

Objective: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. Methods: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). Results: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. Conclusion: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

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HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

Journal of Nutrition and Metabolism ◽

10.1155/2014/980547 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 18

Author(s):

Zeid Khitan ◽

Mohit Harsh ◽

Komal Sodhi ◽

Joseph I. Shapiro ◽

Nader G. Abraham

Keyword(s):

Adipose Tissue ◽

Wnt Signaling ◽

Signaling Pathway ◽

Metabolic Pathway ◽

Lipid Droplets ◽

Wnt Signaling Pathway ◽

Human Mscs ◽

Antioxidant Gene ◽

High Fructose Diet ◽

High Fructose

Background.Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS. HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes. We examined whether the fructose-mediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction of HO-1 would decrease both isoprostane levels and adipogenesis.Methods and Results.We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets (P<0.05). Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects and markedly increased HO-1 and the Wnt signaling pathway. The high fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels (P<0.05versus control). Fructose diets decreased HO-1 and adiponectin levels in adipose tissue. Induction of HO-1 by CoPP decreased isoprostane synthesis (P<0.05versus fructose).Conclusion.Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1.

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Jiang Gui Fang activated interscapular brown adipose tissue and induced epididymal white adipose tissue browning through the PPARγ/SIRT1-PGC1α pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2019.112271 ◽

2020 ◽

Vol 248 ◽

pp. 112271 ◽

Cited By ~ 4

Author(s):

Yu-xin Zu ◽

Hong-yuan Lu ◽

Wen-wu Liu ◽

Xiao-wen Jiang ◽

Yuan Huang ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

Interscapular Brown Adipose Tissue ◽

Brown Adipose ◽

Epididymal White Adipose Tissue ◽

Tissue Browning

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Plasma Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Brown Adipose Tissue Activity in Humans

Metabolites ◽

10.3390/metabo10100388 ◽

2020 ◽

Vol 10 (10) ◽

pp. 388

Author(s):

Angie S. Xiang ◽

Corey Giles ◽

Rebecca K.C. Loh ◽

Melissa F. Formosa ◽

Nina Eikelis ◽

...

Keyword(s):

Adipose Tissue ◽

Docosahexaenoic Acid ◽

Eicosapentaenoic Acid ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Surrogate Marker ◽

Omega 3 ◽

Bat Activity ◽

Brown Adipose ◽

Lipid Species

Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify individual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. Individually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.

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Effects of Ca2+ and Mg2+ on the activity of pyruvate dehydrogenase phosphate phosphatase within toluene-permeabilized mitochondria

Biochemical Journal ◽

10.1042/bj2410371 ◽

1987 ◽

Vol 241 (2) ◽

pp. 371-377 ◽

Cited By ~ 18

Author(s):

P J Midgley ◽

G A Rutter ◽

A P Thomas ◽

R M Denton

Keyword(s):

Adipose Tissue ◽

Small Molecules ◽

White Adipose Tissue ◽

Pyruvate Dehydrogenase ◽

Maximum Rate ◽

Major Effect ◽

Lag Phase ◽

Inhibitory Effects ◽

Highly Sensitive ◽

Epididymal White Adipose Tissue

Mitochondria from rat epididymal white adipose tissue were made permeable to small molecules by toluene treatment and were used to investigate the effects of Mg2+ and Ca2+ on the re-activation of pyruvate dehydrogenase phosphate by endogenous phosphatase. Re-activation of fully phosphorylated enzyme after addition of 0.18 mM-Mg2+ showed a marked lag of 5-10 min before a maximum rate of reactivation was achieved. Increasing the Mg2+ concentration to 1.8 mM (near saturating) or the addition of 100 microM-Ca2+ resulted in loss of the lag phase, which was also greatly diminished if pyruvate dehydrogenase was not fully phosphorylated. It is concluded that, within intact mitochondria, phosphatase activity is highly sensitive to the degree of phosphorylation of pyruvate dehydrogenase and that the major effect of Ca2+ may be to overcome the inhibitory effects of sites 2 and 3 on the dephosphorylation of site 1. Apparent K0.5 values for Mg2+ and Ca2+ were determined from the increases in pyruvate dehydrogenase activity observed after 5 min. The K0.5 for Mg2+ was diminished from 0.60 mM at less than 1 nM-Ca2+ to 0.32 mM at 100 microM-Ca2+; at 0.18 mM-Mg2+, the K0.5 for Ca2+ was 0.40 microM. Ca2+ had little or no effect at saturating Mg2+ concentrations. Since effects of Ca2+ are readily observed in intact coupled mitochondria, it follows that Mg2+ concentrations within mitochondria are sub-saturating for pyruvate dehydrogenase phosphate phosphatase and hence less than 0.5 mM.

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Effects of exercise training on adipogenesis of stromal-vascular fraction cells in rat epididymal white adipose tissue

Acta Physiologica ◽

10.1111/j.1748-1708.2010.02159.x ◽

2010 ◽

pp. no-no ◽

Cited By ~ 1

Author(s):

Takuya Sakurai ◽

Satohiro Endo ◽

Daisuke Hatano ◽

Junetsu Ogasawara ◽

Takako Kizaki ◽

...

Keyword(s):

Adipose Tissue ◽

Exercise Training ◽

White Adipose Tissue ◽

Stromal Vascular Fraction ◽

Epididymal White Adipose Tissue

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Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels

Journal of Endocrinology ◽

10.1677/joe-08-0278 ◽

2008 ◽

Vol 199 (1) ◽

pp. 33-40 ◽

Cited By ~ 56

Author(s):

Andrea Anedda ◽

Eduardo Rial ◽

M Mar González-Barroso

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Uncoupling Protein ◽

Acid Oxidation ◽

Protein Levels ◽

White Adipocytes ◽

Epididymal White Adipose Tissue ◽

Amp Activated Protein Kinase

Metformin is a drug widely used to treat type 2 diabetes. It enhances insulin sensitivity by improving glucose utilization in tissues like liver or muscle. Metformin inhibits respiration, and the decrease in cellular energy activates the AMP-activated protein kinase that in turn switches on catabolic pathways. Moreover, metformin increases lipolysis and β-oxidation in white adipose tissue, thereby reducing the triglyceride stores. The uncoupling proteins (UCPs) are transporters that lower the efficiency of mitochondrial oxidative phosphorylation. UCP2 is thought to protect against oxidative stress although, alternatively, it could play an energy dissipation role. The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes. We studied the effect of this drug in differentiating 3T3-L1 adipocytes and found that metformin causes oxidative stress since it increases the levels of reactive oxygen species (ROS) and lowers the aconitase activity. Variations in UCP2 protein levels parallel those of ROS. Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased. Hence, UCP2 does not appear to be needed to facilitate fatty acid oxidation. Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue. We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.

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