scholarly journals Sinapic Acid Promotes Browning of 3T3-L1 Adipocytes via p38 MAPK/CREB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
In-Seon Bae ◽  
Sang Hoon Kim
Keyword(s):  
Oxidative Phosphorylation ◽  
P38 Mapk ◽  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Sinapic Acid ◽  
Mitogen Activated Protein Kinase ◽  
Marker Genes ◽  
Peroxisome Proliferator ◽  
High Concentration ◽  
Beige Adipocytes

Sinapic acid is a plant-derived phenolic compound, which acts as an antioxidant, anticancer, and anti-inflammatory agent. Although sinapic acid is valuable in a variety of therapeutic applications, its role in the improvement of obesity-related metabolic disease is relatively unexplored. Brown-like adipocytes (beige adipocytes) are characterized by a high concentration of mitochondria and high expression of uncoupling protein 1 (UCP1), which has specific functions in energy expenditure and thermogenesis. This study assessed the browning effects of sinapic acid in 3T3-L1 adipocytes. We investigated the expression of beige marker genes in 3T3-L1 adipocytes treated with sinapic acid. Sinapic acid increased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and UCP1. Sinapic acid also promoted mitochondrial biogenesis by dose-dependently upregulating the oxygen consumption rate and enhancing the expression of representative subunits of oxidative phosphorylation complexes. In addition, treatment with p38 mitogen-activated protein kinase (MAPK) inhibitor and cAMP response element binding (CREB) inhibitor decreased the expressions of genes associated with thermogenesis, mitochondrial biogenesis, and oxidative phosphorylation. In summary, sinapic acid initiates browning 3T3-L1 adipocytes via the p38 MAPK/CREB signaling pathway. Thus, sinapic acid may have potential therapeutic implication in obesity.

scholarly journals Lipocalin 2 regulates retinoic acid-induced activation of beige adipocytes

2018 ◽  
Vol 61 (3) ◽  
pp. 115-126 ◽  
Author(s):  
Jessica A Deis ◽  
Hong Guo ◽  
Yingjie Wu ◽  
Chengyu Liu ◽  
David A Bernlohr ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Retinoic Acid ◽  
Uncoupling Protein ◽  
Oxidative Capacity ◽  
Mitogen Activated Protein Kinase ◽  
Peroxisome Proliferator ◽  
Lipocalin 2 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose ◽  
Beige Adipocytes

Lipocalin-2 (LCN2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for LCN2 in the recruitment and retinoic acid-induced activation of brown-like or ‘beige’ adipocytes. We found LCN2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived from Lcn2 −/− mice. Lcn2 −/− inguinal adipocytes have attenuated insulin-induced upregulation of thermogenic gene expression and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway activation. This is accompanied by a lower basal and maximal oxidative capacity in Lcn2 −/− inguinal adipocytes, indicating mitochondrial dysfunction. Recombinant Lcn2 was able to restore insulin-induced p38MAPK phosphorylation in both WT and Lcn2 −/− inguinal adipocytes. Rosiglitazone treatment during differentiation of Lcn2 −/− adipocytes is able to recruit beige adipocytes at a normal level, however, further activation of beige adipocytes by insulin and RA is impaired in the absence of LCN2. Further, the synergistic effect of insulin and RA on UCP1 and PGC-1α expression is markedly reduced in Lcn2 −/− inguinal adipocytes. Most intriguingly, LCN2 and the retinoic acid receptor-alpha (RAR-α) are concurrently translocated to the plasma membrane of adipocytes in response to insulin, and this insulin-induced RAR-α translocation is absent in adipocytes deficient in LCN2. Our data suggest a novel LCN2-mediated pathway by which RA and insulin synergistically regulates activation of beige adipocytes via a non-genomic pathway of RA action.

scholarly journals Dopamine directly increases mitochondrial mass and thermogenesis in brown adipocytes

2017 ◽  
Vol 58 (2) ◽  
pp. 57-66 ◽  
Author(s):  
Rose Kohlie ◽  
Nina Perwitz ◽  
Julia Resch ◽  
Sebastian M Schmid ◽  
Hendrik Lehnert ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Brown Adipocytes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Mass ◽  
Brown Adipose

Brown adipose tissue (BAT) is key to energy homeostasis. By virtue of its thermogenic potential, it may dissipate excessive energy, regulate body weight and increase insulin sensitivity. Catecholamines are critically involved in the regulation of BAT thermogenesis, yet research has focussed on the effects of noradrenaline and adrenaline. Some evidence suggests a role of dopamine (DA) in BAT thermogenesis, but the cellular mechanisms involved have not been addressed. We employed our extensively characterised murine brown adipocyte cells. D1-like and D2-like receptors were detectable at the protein level. Stimulation with DA caused an increase in cAMP concentrations. Oxygen consumption rates (OCR), mitochondrial membrane potential (Δψm) and uncoupling protein 1 (UCP1) levels increased after 24 h of treatment with either DA or a D1-like specific receptor agonist. A D1-like receptor antagonist abolished the DA-mediated effect on OCR, Δψm and UCP1. DA induced the release of fatty acids, which did not additionally alter DA-mediated increases of OCR. Mitochondrial mass (as determined by (i) CCCP- and oligomycin-mediated effects on OCR and (ii) immunoblot analysis of mitochondrial proteins) also increased within 24 h. This was accompanied by an increase in peroxisome proliferator-activated receptor gamma co-activator 1 alpha protein levels. Also, DA caused an increase in p38 MAPK phosphorylation and pharmacological inhibition of p38 MAPK abolished the DA-mediated effect on Δψm. In summary, our study is the first to reveal direct D1-like receptor and p38 MAPK-mediated increases of thermogenesis and mitochondrial mass in brown adipocytes. These results expand our understanding of catecholaminergic effects on BAT thermogenesis.

scholarly journals Bifidobacterium animalis subsp. lactis A6 Alleviates Obesity Associated with Promoting Mitochondrial Biogenesis and Function of Adipose Tissue in Mice

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1490
Author(s):  
Yanxiong Huo ◽  
Xuhong Lu ◽  
Xiaoyu Wang ◽  
Xifan Wang ◽  
Lingli Chen ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Positive Control ◽  
Peroxisome Proliferator ◽  
Adipose Tissues ◽  
Peroxisome Proliferator Activated Receptor ◽  
Bifidobacterium Animalis ◽  
Mitochondrial Biosynthesis ◽  
And Function ◽  
Estrogen Related Receptor

Probiotics are widely known for their health benefits. Mitochondrial dysfunction is related to obesity. The aim of this study was to illuminate whether Bifidobacterium animalis subsp. lactis A6 (BAA6) could improve obesity due to increased mitochondrial biogenesis and function of adipose tissues. Four-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 17 weeks. For the final eight weeks, the HFD group was divided into three groups including HFD, HFD with BAA6 (HFD + BAA6 group), and HFD with Akkermansia muciniphila (AKK) (HFD + AKK group as positive control). The composition of the microbiota, serum lipopolysaccharides (LPS), and mitochondrial biosynthesis and function of epididymal adipose tissues were measured. Compared with the HFD group, body weight, relative fat weight, the relative abundance of Oscillibacter and Bilophila, and serum LPS were significantly decreased in the HFD + BAA6 and HFD + AKK groups (p < 0.05). Furthermore, the addition of BAA6 and AKK increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) (by 21.53- and 18.51-fold), estrogen-related receptor α (ERRα) (by 2.83- and 1.24-fold), and uncoupling protein-1 (UCP-1) (by 1.51- and 0.60-fold) in epididymal adipose tissues. Our results suggest that BAA6 could improve obesity associated with promoting mitochondrial biogenesis and function of adipose tissues in mice.

Recombinant globular adiponectin inhibits lipid deposition by p38 MAPK/ATF-2 and TOR/p70 S6 kinase pathways in chicken adipocytes

2014 ◽  
Vol 92 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Yan Jun ◽  
Tan Xiao ◽  
Yan Guoyong ◽  
Feng Min ◽  
Yang Haili ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Fatty Acid Synthase ◽  
Marker Gene ◽  
Mitogen Activated Protein Kinase ◽  
Marker Genes ◽  
Lipid Deposition ◽  
S6 Kinase ◽  
P70 S6 Kinase ◽  
Mitogen Activated Protein ◽  
Globular Adiponectin

Adiponectin plays a fundamental role in lipid and carbohydrate metabolism. However, its role in adipocyte differentiation remains controversial. To investigate the effect of gAd on lipid deposition in chicken adipocytes and its related signaling pathways, 200 μg/mL recombinant globular adiponectin, isoproterenol, SB253580, leucine, and rapamycin were used to treat chicken adipocytes. Results demonstrated that gAd increased the expression of endogenous adiponectin and AdipoR1 (P < 0.01); gAd inhibited triglyceride (TG) accumulation in chicken adipocyte and increased the release of free fatty acids (FFA) in medium; gAd decreased the expression of adipogenic marker genes CCAAT/enhancer binding protein alpha (C/EBPα) and fatty acid synthase (FAS), while activating the expression of lipolytic marker gene adipose triglyceride lipase (ATGL) (P < 0.01). Meanwhile, gAd activated the phosphorylation levels of p38 mitogen-activated protein kinase (p38 MAPK) and activating transcription factor 2 (ATF-2), and suppressed the phosphorylation levels of rapamycin (TOR) and p70 S6 Kinase (P < 0.01). In conclusion, the results demonstrate that gAd has an ability to inhibit lipids deposition in chicken adipocyte, which depends on the p38 MAPK/ATF–2 and TOR/p70 S6 Kinase pathways.

scholarly journals Sesamol promotes browning of white adipocytes to ameliorate obesity by inducing mitochondrial biogenesis and inhibition mitophagy via β3-AR/PKA signaling pathway

2021 ◽  
Author(s):  
Cui Lin ◽  
Jihua Chen ◽  
Minmin Hu ◽  
Wenya Zheng ◽  
Ziyu Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Total Cholesterol ◽  
Protein Kinase A ◽  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Obese Mice ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Kinase A

Background: Obesity is defined as an imbalance between energy intake and expenditure, and it is a serious risk factor of non-communicable diseases. Recently many studies have shown that promoting browning of white adipose tissue (WAT) to increase energy consumption has a great therapeutic potential for obesity. Sesamol, a lignan from sesame oil, had shown potential beneficial functions on obesity treatment. Objective: In this study, we used C57BL/6J mice and 3T3-L1 adipocytes to investigate the effects and the fundamental mechanisms of sesamol in enhancing the browning of white adipocytes to ameliorate obesity. Methods: Sixteen-week-old C57BL/6J male mice were fed high-fat diet (HFD) for 8 weeks to establish the obesity models. Half of the obese mice were administered with sesamol (100 mg/kg body weight [b.w.]/day [d] by gavage for another 8 weeks. Triacylglycerol (TG) and total cholesterol assay kits were used to quantify serum TG and total cholesterol (TC). Oil red O staining was used to detect lipid droplet in vitro. Mito-Tracker Green was used to detect the mitochondrial content. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the levels of beige-specific genes. Immunoblotting was used to detect the proteins involved in beige adipocytes formation. Results: Sesamol decreased the content of body fat and suppressed lipid accumulation in HFD-induced obese mice. In addition, sesamol significantly upregulated uncoupling protein-1 (UCP1) protein in adipose tissue. Further research found that sesamol also significantly activated the browning program in mature 3T3-L1 adipocytes, manifested by the increase in beige-specific genes and proteins. Moreover, sesamol greatly increased mitochondrial biogenesis, as proved by the upregulated protein levels of mitochondrial biogenesis, and the inhibition of the proteins associated with mitophagy. Furthermore, β3-adrenergic receptor (β3-AR), protein kinase A-C (PKA-C) and Phospho-protein kinase A (p-PKA) substrate were elevated by sesamol, and these effects were abolished by the pretreatment of antagonists β3-AR. Conclusion: Sesamol promoted browning of white adipocytes by inducing mitochondrial biogenesis and inhibiting mitophagy through the β3-AR/PKA pathway. This preclinical data promised the potential to consider sesamol as a metabolic modulator of HFD-induced obesity.

scholarly journals Fruit of Gardenia jasminoides Induces Mitochondrial Activation and Non-Shivering Thermogenesis through Regulation of PPARγ

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1418
Author(s):  
Woo Yong Park ◽  
Gahee Song ◽  
Ja Yeon Park ◽  
Kwan-Il Kim ◽  
Kwang Seok Ahn ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Exposure Model ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Gardenia Jasminoides ◽  
White Adipocytes ◽  
Beige Adipocytes ◽  
Underlying Mechanisms ◽  
Induced Changes

The extract of the Gardenia jasminoides fruit (GJFE) can been consumed as an herbal tea or used as a yellow dye. Recently, studies report that GFJE exerts inhibitory effects on lipid accumulation and adipogenesis in white adipocytes. We evaluated the thermogenic actions of GJFE by focusing on mitochondrial activation and studying the underlying mechanisms. To investigate the role of GJFE on thermogenesis in mice, we used an acute cold exposure model. After 2 weeks of feeding, the cold tolerance of GJFE-fed mice was notably increased compared to PBS-fed mice. This was due to an increase in thermogenic proteins in the inguinal white adipose tissue of the cold-exposed mice. Moreover, GJFE significantly increased thermogenic factors such as peroxisome proliferator-activated receptor gamma (PPARγ), uncoupling protein 1 (UCP1), and PPARγ coactivator 1 alpha (PGC1α) in vitro as well. Factors related to mitochondrial abundance and functions were also induced by GJFE in white and beige adipocytes. However, the treatment of PPARγ inhibitor abolished the GJFE-induced changes, indicating that activation of PPARγ is critical for the thermogenic effect of GJFE. In conclusion, GJFE induces thermogenic action by activating mitochondrial function via PPARγ activation. Through these findings, we suggest GJFE as a potential anti-obesity agent with a novel mechanism involving thermogenic action in white adipocytes.

Effects of Deep Sea Water on Anti-Obesity Properties in Induction of Beige Adipocytes

2019 ◽  
Vol 13 (1) ◽  
pp. 38-48
Author(s):  
Samihah Z.M. Nani ◽  
Abubakar Jaafar ◽  
Fadzilah A.A. Majid ◽  
Akbariah Mahdzir ◽  
Md. Nor Musa
Keyword(s):  
Adipose Tissue ◽  
Deep Sea ◽  
Sea Water ◽  
Binding Protein ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Deep Sea Water ◽  
Beige Adipocytes

Objective: Deep sea water (DSW) accumulates many scientific shreds of evidence in treating obesity. Previous studies indicated that it reduces white adipose tissue (WAT) and body weight. WAT is energy storage fat, while beige adipose tissue is energy supply fat. In this study, the effects of DSW in the induction of beige adipocytes from mouse adipose tissue-derived stromal vascular fraction (SVF) cells are determined. Methods: Adipose tissue-derived SVF cells were isolated from mice and used for induction of beige adipocytes and treated with DSW at several concentrations. Results: During the course of beige adipocytes differentiation, DSW treatment increased lipid accumulation and upregulated adipogenic genes markers expression such as peroxisome proliferator-activated receptor-&#947; (PPAR-&#947;), CCAAT/enhancer-binding protein a (C/EBP-&#945;), and fatty acid binding protein 4 (FABP4), and also upregulated thermogenic genes markers such as the uncoupling protein 1 (UCP-1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1&#945;), and cell deathinducing DFFA-like effector A (Cidea) in beige adipocytes. Conclusion: DSW has the potential to promote browning of WAT and upregulates the thermogenic genes that are responsible for energy expenditure.

Screening of flavor compounds using Ucp1-luciferase reporter beige adipocytes identified 5-methylquinoxaline as a novel UCP1-inducing compoundsss

2021 ◽  
Author(s):  
Satoko Kawarasaki ◽  
Kazuki Matsuo ◽  
Hidetoshi Kuwata ◽  
Lanxi Zhou ◽  
Jungin Kwon ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Whole Body ◽  
Flavor Compounds ◽  
Luciferase Reporter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beige Adipocytes ◽  
Ucp1 Expression

Abstract Uncoupling protein 1 (UCP1) in brown or beige adipocytes is a mitochondrial protein that is expected to enhance whole-body energy expenditure. For the high-throughput screening of UCP1 transcriptional activity regulator, we established a murine inguinal white adipose tissue-derived Ucp1-luciferase reporter preadipocyte line. Using this reporter preadipocyte line, 654 flavor compounds were screened, and a novel Ucp1 expression-inducing compound, 5-methylquinoxaline, was identified. Adipocytes treated with 5-methylquinoxaline showed increased Ucp1 mRNA expression levels and enhanced oxygen consumption. 5-methylquinoxaline induced Ucp1 expression through peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and 5-methylquinoxaline-induced PGC1α activation seemed to be partially regulated by its phosphorylation or deacetylation. Thus, our Ucp1-luciferase reporter preadipocyte line is a useful tool for screening of Ucp1 inductive compounds.

scholarly journals Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice

2016 ◽  
Vol 310 (8) ◽  
pp. E676-E687 ◽  
Author(s):  
Tomoya Sakamoto ◽  
Takahiro Nitta ◽  
Koji Maruno ◽  
Yu-Sheng Yeh ◽  
Hidetoshi Kuwata ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Cold Exposure ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Whole Body ◽  
Marker Genes ◽  
Adipose Tissues ◽  
Expression Levels ◽  
Beige Adipocytes ◽  
Thermogenic Adipocytes

Emergence of thermogenic adipocytes such as brown and beige adipocytes is critical for whole body energy metabolism. Promoting the emergence of these adipocytes, which increase energy expenditure, could be a viable strategy in treating obesity and its related diseases. However, little is known regarding the mechanisms that regulate the emergence of these adipocytes in obese adipose tissue. Here, we demonstrated that classically activated macrophages (M1 Mϕ) suppress the induction of thermogenic adipocytes in obese adipose tissues of mice. Cold exposure significantly induced the expression levels of uncoupling protein-1 (UCP1), which is a mitochondrial protein unique in thermogenic adipocytes, in C57BL/6 mice fed a normal diet. However, UCP1 induction was significantly suppressed in adipose tissues of C57BL/6 mice fed a high-fat diet, into which M1 Mϕ infiltrated. Depletion of M1 Mϕ using clodronate liposomes eliminated the suppressive effect and markedly reduced the mRNA level of tumor necrosis factor-α (TNFα) in the adipose tissues. Importantly, consistent with the observed changes in the expression levels of marker genes for thermogenic adipocytes, combination treatment of clodronate liposome and cold exposure resulted in metabolic benefits such as lowered body weight and blood glucose level in obese mice. Moreover, intraperitoneal injection of recombinant TNFα protein suppressed UCP1 induction in lean adipose tissues of mice. Collectively, our data indicate that infiltrated M1 Mϕ suppress the induction of thermogenic adipocytes in obese adipose tissues via TNFα. This report suggests that inflammation induced by infiltrated Mϕ could cause not only insulin resistance but also reduction of energy expenditure in adipose tissues.

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