3308The critical roles of coagulation factors in inducing brown adipose tissue dysfunction and systemic metabolic disorder in obesity

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Hayashi ◽  
I S Shimizu ◽  
Y Y Yoshida ◽  
R I Ikegami ◽  
G K Katsuumi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Membrane Potential ◽  
Glucose Intolerance ◽  
Metabolic Disorder ◽  
Metabolic Disorders ◽  
Metabolic Stress ◽  
Coagulation Factor ◽  
Brown Adipose ◽  
Thermogenic Response

Abstract Obese individuals are predisposed to cardio-metabolic disorders. Brown adipose tissue (BAT) is an active metabolic organ abundant with mitochondria, and studies suggest a potential role of BAT in the maintenance of metabolic health in rodents and humans. Metabolic stress causes BAT dysfunction, but the underlying mechanisms are largely unknown. Coagulation factor Xa (FXa) is critically involved in a coagulation cascade, and it is also known to mediate biological effects by the activation of protease-activated receptor (PAR)-signaling. Accumulating evidence shows that PAR1 contributes to tissue remodeling in cardiovascular system. Here we show a previously unknown role of FXa-PAR signaling in promoting BAT dysfunction and systemic metabolic disorder in a murine dietary obese model. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in tissue factor (TF), coagulation factor VII and FXa in BAT. TF-FVIIa (activated form of FVII)-FXa complex is known to activate PAR1, and we found a significant increase in PAR1 expression in BAT upon metabolic stress. Administration of a FXa inhibitor ameliorated BAT whitening, improved thermogenic response and systemic glucose intolerance upon dietary obesity. In contrast, administration of warfarin did not show any phenotype in BAT. BAT specific TF and PAR1 over-expression model showed significant whitening of this tissue, which was associated with systemic glucose intolerance. BAT specific PAR1 KO mice improved glucose intolerance and thermogenic response under a metabolically stressed condition. In differentiated brown adipocytes, FXa markedly increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial membrane potential. Inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. We also found that plasma FXa level did not increase in obese mice as well as in obese individuals. These results suggest the previously unknown role of coagulation systems in promoting BAT dysfunction, leading to systemic metabolic disorders. Maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes.

The crucial roles of coagulation factors in inducing brown adipose tissue dysfunction and systemic metabolic disorder in obesity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hayashi ◽  
I Shimizu ◽  
Y Yoshida ◽  
G Katsuumi ◽  
M Suda ◽  
...  
Keyword(s):  
Glucose Intolerance ◽  
Metabolic Disorders ◽  
Metabolic Stress ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Mitochondrial Ros ◽  
Brown Adipose ◽  
Thermogenic Response

Abstract   The prevalence of obesity is increasing worldwide. Obese individuals are predisposed to cardio-metabolic disorders. Brown adipose tissue (BAT) is an active metabolic organ abundant with mitochondria, and studies suggest a potential role of BAT in the maintenance of metabolic health in rodents and humans. Metabolic stress causes BAT dysfunction, but the underlying mechanisms are largely unknown. Coagulation factor Xa (FXa) is critically involved in a coagulation cascade, and it is also known to mediate biological effects by the activation of protease-activated receptor (PAR)-signaling. Accumulating evidence shows that PAR1 contributes to tissue remodeling in cardiovascular system. Analyzing deposited microarray data, we found transcripts for coagulation factors including factor VII (F7), factor X (F10), and PAR1 receptor were increased in BAT from obese mice. Here we show a previously unknown role of FXa-PAR signaling in promoting BAT dysfunction and systemic metabolic disorder in a murine dietary obese model. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in tissue factor (TF), coagulation factor VII and FXa in BAT. TF-FVIIa (activated form of FVII)-FXa complex is known to activate PAR1, and we found a significant increase in PAR1 expression in BAT upon metabolic stress. Administration of a FXa inhibitor ameliorated BAT whitening, improved thermogenic response and systemic glucose intolerance upon dietary obesity. Fxa inhibition reduced reactive oxygen species (ROS) level in BAT. In contrast, administration of warfarin did not show any phenotype in BAT. BAT specific TF and PAR1 over-expression model showed significant whitening of this tissue, which was associated with systemic glucose intolerance. We generated BAT specific PAR1 KO mice. BAT-PAR1 KO mice exhibited re-browning of BAT along with reduced ROS level in this tissue. In BAT-PAR1 KO mice, glucose intolerance and thermogenic response under a metabolically stressed condition were ameliorated. In differentiated brown adipocytes, FXa markedly increased mitochondrial ROS and reduced mitochondrial membrane potential. Inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. We also found that plasma FXa level did not increase in obese mice as well as in obese individuals. These results suggest the previously unknown role of coagulation systems in promoting BAT dysfunction, leading to systemic metabolic disorders. Maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes. Funding Acknowledgement Type of funding source: None

Central Role of Brown Adipose Tissue Thyroxine 5′-Deiodinase on Thyroid Hormone-Dependent Thermogenic Response to Cold*

Endocrinology ◽  
1991 ◽  
Vol 128 (4) ◽  
pp. 2149-2159 ◽  
Author(s):  
SUZY D. CARVALHO ◽  
EDNA T. KIMURA ◽  
ANTONIO C. BIANCO ◽  
J. ENRIQUE SILVA
Keyword(s):  
Adipose Tissue ◽  
Thyroid Hormone ◽  
Brown Adipose Tissue ◽  
Brown Adipose ◽  
Thermogenic Response

scholarly journals Elucidating the Regulatory Role of Melatonin in Brown, White, and Beige Adipocytes

2019 ◽  
Author(s):  
Ziye Xu ◽  
Wenjing You ◽  
Jiaqi Liu ◽  
Yizhen Wang ◽  
Tizhong Shan
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Tissue Mass ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Beige Adipocytes

AbstractThe high prevalence of obesity and its associated metabolic diseases has heightened the importance of understanding control of adipose tissue development and energy metabolism. In mammals, 3 types of adipocytes with different characteristics and origins have been identified: white, brown, and beige. Beige and brown adipocytes contain numerous mitochondria and have the capability to burn energy and counteract obesity, while white adipocytes store energy and are closely associated with metabolic disorders and obesity. Thus, regulation of the development and function of different adipocytes is important for controlling energy balance and combating obesity and related metabolic disorders. Melatonin is a neurohormone, which plays multiple roles in regulating inflammation, blood pressure, insulin actions, and energy metabolism. This article summarizes and discusses the role of melatonin in white, beige, and brown adipocytes, especially in affecting adipogenesis, inducing beige formation or white adipose tissue browning, enhancing brown adipose tissue mass and activities, improving anti-inflammatory and antioxidative effects, regulating adipokine secretion, and preventing body weight gain. Based on the current findings, melatonin is a potential therapeutic agent to control energy metabolism, adipogenesis, fat deposition, adiposity, and related metabolic diseases.

P53 regulates the lipid metabolism response to metabolic stress in brown adipose tissue

2020 ◽  
Author(s):  
G Lenihan-Geels ◽  
F Garcia-Carrizo ◽  
C Li ◽  
M Oster ◽  
A Prokesch ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Brown Adipose Tissue ◽  
Metabolic Stress ◽  
Brown Adipose

142-OR: Unique Role of the a4 Component for S6-Kinase Activity in Metabolic Regulation and Anti-apoptotic Effect in Brown Adipose Tissue

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 142-OR
Author(s):  
MASAJI SAKAGUCHI ◽  
SHOTA OKAGAWA ◽  
SAYAKA KITANO ◽  
TATSUYA KONDO ◽  
EIICHI ARAKI
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Metabolic Regulation ◽  
Kinase Activity ◽  
S6 Kinase ◽  
Unique Role ◽  
Brown Adipose ◽  
Apoptotic Effect

scholarly journals Adipose Tissue Immunomodulation and Treg/Th17 Imbalance in the Impaired Glucose Metabolism of Children with Obesity

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 554
Author(s):  
Stefania Croce ◽  
Maria Antonietta Avanzini ◽  
Corrado Regalbuto ◽  
Erika Cordaro ◽  
Federica Vinci ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Th17 Cells ◽  
Metabolic Disorders ◽  
Potential Role ◽  
Immune Monitoring ◽  
Metabolic Dysfunction ◽  
Impaired Glucose Metabolism ◽  
T Cell Infiltration

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

The endocrine role of brown adipose tissue: An update on actors and actions

2021 ◽  
Author(s):  
Aleix Gavaldà-Navarro ◽  
Joan Villarroya ◽  
Rubén Cereijo ◽  
Marta Giralt ◽  
Francesc Villarroya
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Adipose

scholarly journals Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

2021 ◽  
Vol 22 (11) ◽  
pp. 5560
Author(s):  
Alejandro Álvarez-Artime ◽  
Belén García-Soler ◽  
Rosa María Sainz ◽  
Juan Carlos Mayo
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Tumor Development ◽  
Cell Types ◽  
Protective Role ◽  
Bioactive Molecules ◽  
Brown Adipose ◽  
Endocrine Organs

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer.

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