AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice

Endocrine ◽  
2016 ◽  
Vol 55 (3) ◽  
pp. 786-798 ◽  
Author(s):  
Francielle Graus-Nunes ◽  
Tamiris Lima Rachid ◽  
Felipe de Oliveira Santos ◽  
Sandra Barbosa-da-Silva ◽  
Vanessa Souza-Mello
Keyword(s):  
Adipose Tissue ◽  
Receptor Antagonist ◽  
White Adipose Tissue ◽  
At1 Receptor ◽  
Obese Mice ◽  
Beige Adipocytes

scholarly journals Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 253 ◽  
Author(s):  
Yu-Sheng Chen ◽  
Hsuan-Miao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Dysfunction ◽  
Ursodeoxycholic Acid ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Bile Acid Metabolism ◽  
Obese Mice ◽  
Alcoholic Fatty Liver ◽  
Tissue Macrophage ◽  
Stat3 Phosphorylation

Obesity has been shown to play a role in the pathogenesis of several forms of metabolic syndrome, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. Ursodeoxycholic acid (UDCA) has been shown to possess antioxidant and anti-inflammatory properties and prevents mitochondrial dysfunction in the progression of obesity-associated diseases. The aim of the study was to evaluate the mechanisms of UDCA during obesity-linked hepatic mitochondrial dysfunction and obesity-associated adipose tissue macrophage-induced inflammation in obese mice. UDCA significantly decreased lipid droplets, reduced free fatty acids (FFA) and triglycerides (TG), improved mitochondrial function, and enhanced white adipose tissue browning in ob/ob mice. This is associated with increased hepatic energy expenditure, mitochondria biogenesis, and incorporation of bile acid metabolism (Abca1, Abcg1 mRNA and BSEP, FGFR4, and TGR5 protein). In addition, UDCA downregulated NF-κB and STAT3 phosphorylation by negative regulation of the expression of SOCS1 and SOCS3 signaling. These changes were accompanied by decreased angiogenesis, as shown by the downregulation of VEGF, VCAM, and TGF-βRII expression. Importantly, UDCA is equally effective in reducing whole body adiposity. This is associated with decreased adipose tissue expression of macrophage infiltration (CD11b, CD163, and CD206) and lipogenic capacity markers (lipofuscin, SREBP-1, and CD36). Furthermore, UDCA significantly upregulated adipose browning in association with upregulation of SIRT-1-PGC1-α signaling in epididymis adipose tissue (EWAT). These results suggest that multi-targeted therapies modulate glucose and lipid biosynthesis fluxes, inflammatory response, angiogenesis, and macrophage differentiation. Therefore, it may be suggested that UDCA treatment may be a novel therapeutic agent for obesity.

scholarly journals Resveratrol-Induced White Adipose Tissue Browning in Obese Mice by Remodeling Fecal Microbiota

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3356 ◽  
Author(s):  
Weiyao Liao ◽  
Xiaohan Yin ◽  
Qingrong Li ◽  
Hongmin Zhang ◽  
Zihui Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gut Microbiota ◽  
White Adipose Tissue ◽  
Additional Treatment ◽  
The Body ◽  
Sirtuin 1 ◽  
Obese Mice ◽  
Positive Role ◽  
White Fat

Promoting the browning of white fat may be a potential means of combating obesity. Therefore, in this study, we investigated the effect of resveratrol (RES) on the body weight and browning of white fat in high-fat diet (HFD)-induced obese mice and the potential associated mechanism in vivo. Eight-week-old male mice were randomized to receive different treatments: (1), chow without any additional treatment (chow); (2), chow plus 0.4% resveratrol (chow-RES); (3), HFD without any additional treatment (HFD); and (4), HFD plus 0.4% resveratrol (HFD-RES). After 4 weeks of feeding, additional 8-week-old male recipient mice were randomly allocated to the following 4 treatments: (5), HFD and received feces from chow-fed mice; (6), HFD and received feces from chow-RES-fed mice; (7), HFD and received feces from HFD-fed mice; and (8), HFD and received feces from HFD-RES-fed mice. RES treatment significantly inhibited increases in fat accumulation, promoted the browning of white adipose tissue (WAT) and alleviated gut microbiota dysbiosis in HFD-fed mice. Subsequent analyses showed that the gut microbiota remodeling induced by resveratrol had a positive role in WAT browning, and sirtuin-1 (Sirt1) signaling appears to be a key component of this process. Overall, the results show that RES may serve as a potential intervention to reduce obesity by alleviating dysbiosis of the gut microbiota.

scholarly journals Pycnogenol® Induces Browning of White Adipose Tissue through the PKA Signaling Pathway in Apolipoprotein E-Deficient Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Huiying Cong ◽  
Wenxia Zhong ◽  
Yiying Wang ◽  
Shoichiro Ikuyama ◽  
Bin Fan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Apolipoprotein E ◽  
Signaling Pathway ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Mrna Level ◽  
Antioxidant Properties ◽  
Expression Of Genes ◽  
Beige Adipocytes ◽  
Deficient Mice

Beige adipocytes in white adipose tissue (WAT) have received considerable recognition because of their potential protective effect against obesity. Pycnogenol (PYC), extracted from French maritime pine bark, has anti-inflammatory and antioxidant properties and can improve lipid profiles. However, the effect of PYC on obesity has never been explored. In this study, we investigated the effects of PYC on obesity and WAT browning in apolipoprotein E- (ApoE-) deficient mice. The results showed that PYC treatment clearly reversed body weight and the mass of eWAT gain resulting from a high-cholesterol and high-fat diet (HCD), but no difference in food intake. The morphology results showed that the size of the adipocytes in the PYC-treated mice was obviously smaller than that in the HCD-fed mice. Next, we found that PYC upregulated the expression of genes related to lipolysis (ATGL and HSL), while it decreased the mRNA level of PLIN1. PYC significantly increased the expression of UCP1 and other genes related to beige adipogenesis. Additionally, PYC increased the expression of proteins related to the protein kinase A (PKA) signaling pathway. The findings suggested that PYC decreased obesity by promoting lipolysis and WAT browning. Thus, PYC may be a novel therapeutic target for obesity.

Osteocalcin improves insulin resistance and inflammation in obese mice: Participation of white adipose tissue and bone

Bone ◽  
2018 ◽  
Vol 115 ◽  
pp. 68-82 ◽  
Author(s):  
J.A.C. Guedes ◽  
J.V. Esteves ◽  
M.R. Morais ◽  
T.M. Zorn ◽  
D.T. Furuya
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Obese Mice

scholarly journals Mechanisms Mediating Dose-Dependent Effects of Eicosapentaenoic Acid in White Adipose Tissue From High Fat Diet-Induced Obese Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1209-1209
Author(s):  
Hanna Davis ◽  
Mandana Pahlavani ◽  
Yujiao Zu ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
White Adipose Tissue ◽  
Macrophage Infiltration ◽  
Low Grade ◽  
Mrna Levels ◽  
Obese Mice ◽  
Adipocyte Size ◽  
M1 Macrophage ◽  
Anti Inflammatory

Abstract Objectives Obesity is a global epidemic and complex disease associated with an expansion of white adipose tissue (WAT). Obesity is accompanied by chronic low-grade inflammation, characterized by elevated levels of secreted pro-inflammatory cytokines and M1 macrophage infiltration into WAT. Eicosapentaenoic acid (EPA), a long-chain omega-3 polyunsaturated fatty acid, has been reported to have anti-obesity and anti-inflammatory properties. Moreover, we previously showed that EPA dose-dependently improved glucose intolerance, and inflammation in diet-induced obese mice. The objective of this study is to further determine mechanisms underlying these metabolic protective effects of EPA in epididymal WAT (e-WAT). Methods Male B6 mice were fed a HF diet (45% kcal fat) or a HF diet supplemented with 9, 18, or 36 g/kg of EPA-enriched fish oil (EPA 9, 18 or 36) for 14 weeks. We performed histological assessments in eWAT to determine adipocyte size; and measure macrophage infiltration by immunohistochemistry using galectin-3. RNA was isolated from eWAT for RNA sequencing and gene expression analyses. Data were analyzed using GraphPad Prism software. Results EPA36-fed mice had significantly lower body weight and fat percentage, compared to HF (P < 0.05). In addition, EPA18 and 36 significantly decreased weight of e-WAT (P < 0.05) and increased glucose clearance compared to HF (P < 0.05). Moreover, all EPA doses had smaller adipocytes (P < 0.05). Compared to HF, EPA18 and 36 significantly reduced macrophage infiltration in e-7.43 fold, respectively. Consistent with these changes, EPA18 and 36 reduced the mRNA levels of HF-induced inflammatory markers, including arachidonate 5-lipoxygenase (Alox5) and leukotriene B4 receptor (Ltb4r) compared to HF (P < 0.05). RNA Seq analyses revealed that EPA18 attenuated HF-induced inflammation in part by up-regulating cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling pathways and down-regulating triggering receptor expressed on myeloid cells 1 (TREM1) signaling. Conclusions EPA dose-dependently ameliorated HF-induced obesity and inflammation by reducing adipocyte size and macrophage infiltration and modulating pro- and anti-inflammatory pathways in e-WAT. These effects were achieved at human equivalent doses, that are currently prescribed for reducing triglycerides. Funding Sources USDA NIFA NIH.

scholarly journals Neuronal Modulation of Brown Adipose Activity Through Perturbation of White Adipocyte Lipogenesis

2018 ◽  
Author(s):  
Adilson Guilherme ◽  
David J Pedersen ◽  
Felipe Henriques ◽  
Alexander H. Bedard ◽  
Elizabeth Henchey ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Fatty Acid Synthase ◽  
Sympathetic Neurons ◽  
Sympathetic Innervation ◽  
Long Distance ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
Beige Adipocytes

ABSTRACTWhite adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of “beige” adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.

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 Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

2019 ◽  
Author(s):  
Devjanee Swain-Lenz ◽  
Alejandro Berrio ◽  
Alexias Safi ◽  
Gregory E. Crawford ◽  
Gregory A. Wray
Keyword(s):  
Adipose Tissue ◽  
Body Fat ◽  
White Adipose Tissue ◽  
Sequence Motif ◽  
Primary Role ◽  
Regulatory Regions ◽  
Comparative Analyses ◽  
White Adipocytes ◽  
Beige Adipocytes

AbstractHumans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using macaque as an outgroup. We find that many cis-regulatory regions that are specifically closed in humans are under positive selection, located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which white adipocytes are transdifferentiated into beige adipocytes. While the primary role of white adipocytes is to store lipids, beige adipocytes are thermogeneic. The collective closing of many putative regulatory regions associated with beiging of fat suggests an adaptive mechanism that increases body fat in humans.

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