scholarly journals DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiyan Zhou ◽  
Xinyi Peng ◽  
Jie Hu ◽  
Liwen Wang ◽  
Hairong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Whole Body ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

scholarly journals Allicin regulates energy homeostasis through brown adipose tissue

2019 ◽  
Author(s):  
Chuanhai Zhang ◽  
Xiaoyun He ◽  
Yao Sheng ◽  
Jia Xu ◽  
Cui Yang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Promising Therapeutic Approach ◽  
Treatment Of Obesity

AbstractBackground/objectives:Disorder of energy homeostasis can lead to a variety of metabolic diseases, especially obesity. Brown adipose tissue (BAT) is a promising potential therapeutic target for the treatment of obesity and related metabolic diseases. Allicin, a main bioactive ingredient in garlic, has multiple biology and pharmacological function. However, the role of Allicin, in the regulation of metabolic organ, especially the role of activation of BAT, has not been well studied. Here, we analyzed the role of Allicin in whole-body metabolism and the activation of BAT.Results:Allicin had a significant effect in inhibiting body weight gain, decreasing adiposity, maintaining glucose homeostasis, improving insulin resistance, and ameliorating hepatic steatosis in diet-introduced obesity (DIO) mice. Then we find that Allicin can strongly activate brown adipose tissue (BAT). The activation of brown adipocyte treated with Allicin was also confirmed in mouse primary brown adipocytes.Conclusion:Allicin can ameliorate obesity through activating brown adipose tissue. Our findings provide a promising therapeutic approach for the treatment of obesity and metabolic disorders.

scholarly journals Senescent T Cell Induces Brown Adipose Tissue “Whitening” Via Secreting IFN-γ

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao-Xi Pan ◽  
Kang-Li Yao ◽  
Yong-Feng Yang ◽  
Qian Ge ◽  
Run Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Adipose Tissue ◽  
T Cell ◽  
Brown Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Critical Role ◽  
Brown Adipocyte ◽  
Brown Adipose ◽  
Ifn Γ ◽  
Old Mice

Aging-associated chronic inflammation is a key contributing factor to a cluster of chronic metabolic disorders, such as cardiovascular disease, obesity, and type 2 diabetes. Immune cells particularly T cells accumulate in adipose tissue with advancing age, and there exists a cross talk between T cell and preadipocyte, contributing to age-related adipose tissue remodeling. Here, we compared the difference in morphology and function of adipose tissue between young (3-month-old) and old (18-month-old) mice and showed the phenomenon of brown adipose tissue (BAT) “whitening” in old mice. Flow cytometry analysis suggested an increased proportion of T cells in BAT of old mice comparing with the young and exhibited senescent characteristics. We take advantage of coculture system to demonstrate directly that senescent T cells inhibited brown adipocyte differentiation of preadipocytes in adipose tissue. Mechanistically, both in vitro and in vivo studies suggested that senescent T cells produced and released a higher level of IFN-γ, which plays a critical role in inhibition of preadipocyte-to-brown adipocyte differentiation. Taken together, the data indicate that senescent T cell-derived IFN-γ is a key regulator in brown adipocyte differentiation.

scholarly journals Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans

2016 ◽  
Vol 40 (11) ◽  
pp. 1655-1661 ◽  
Author(s):  
M Hibi ◽  
S Oishi ◽  
M Matsushita ◽  
T Yoneshiro ◽  
T Yamaguchi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Body Fat ◽  
Whole Body ◽  
Fat Utilization ◽  
Healthy Humans ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

scholarly journals Immunosuppression byN-Methyl-d-Aspartate Receptor Antagonists Is Mediated through Inhibition of Kv1.3 and KCa3.1 Channels in T Cells

2013 ◽  
Vol 34 (5) ◽  
pp. 820-831 ◽  
Author(s):  
Sascha Kahlfuß ◽  
Narasimhulu Simma ◽  
Judith Mankiewicz ◽  
Tanima Bose ◽  
Theresa Lowinus ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neuronal Development ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Th2 Cells ◽  
Effector Cells ◽  
Ifn Γ

N-Methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels that play an important role in neuronal development, plasticity, and excitotoxicity. NMDAR antagonists are neuroprotective in animal models of neuronal diseases, and the NMDAR open-channel blocker memantine is used to treat Alzheimer's disease. In view of the clinical application of these pharmaceuticals and the reported expression of NMDARs in immune cells, we analyzed the drug's effects on T-cell function. NMDAR antagonists inhibited antigen-specific T-cell proliferation and cytotoxicity of T cells and the migration of the cells toward chemokines. These activities correlated with a reduction in T-cell receptor (TCR)-induced Ca2+mobilization and nuclear localization of NFATc1, and they attenuated the activation of Erk1/2 and Akt. In the presence of antagonists, Th1 effector cells produced less interleukin-2 (IL-2) and gamma interferon (IFN-γ), whereas Th2 cells produced more IL-10 and IL-13. However, in NMDAR knockout mice, the presumptive expression of functional NMDARs in wild-type T cells was inconclusive. Instead, inhibition of NMDAR antagonists on the conductivity of Kv1.3 and KCa3.1 potassium channels was found. Hence, NMDAR antagonists are potent immunosuppressants with therapeutic potential in the treatment of immune diseases, but their effects on T cells have to be considered in that Kv1.3 and KCa3.1 channels are their major effectors.

scholarly journals Brown Adipose Tissue - role in metabolic disorders

2019 ◽  
Vol 13 (1) ◽  
pp. 002
Author(s):  
Tahniyah Haq ◽  
Frank Joseph Ong ◽  
Sarah Kanji
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Whole Body ◽  
Positron Emission ◽  
Brown Adipose ◽  
Magnetic Resonance Imaging Mri ◽  
Fdg Pet Ct ◽  
Body Energy

Brown adipose tissue, a thermogenic organ, previously thought to be present in only small mammals and children has recently been identified in adult humans. Located primarily in the supraclavicular and cervical area, it produces heat by uncoupling oxidative phosphorylation due to the unique presence of uncoupling protein 1 by a process called nonshivering thermogenesis. BAT activity depends on many factors including age, sex, adiposity and outdoor temperature. Positron-emission tomography using 18F-fluorodeoxyglucose and computed tomography (18F-FDG PET–CT), magnetic resonance imaging (MRI) and thermal imaging (IRT) are among several methods used to detect BAT in humans. The importance of BAT is due to its role in whole body energy expenditure and fuel metabolism. Thus it is postulated that it may be useful in the treatment of metabolic diseases. However, there are still many unanswered questions to the clinical usefulness of this novel tissue. IMC J Med Sci 2019; 13(1): 002

scholarly journals The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases

2019 ◽  
Vol 20 (19) ◽  
pp. 4924 ◽  
Author(s):  
Lee ◽  
Park ◽  
Oh ◽  
Lee ◽  
Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Brown Adipose

: Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and β-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. Mitochondrial dysfunction in adipocytes has been reported to have strong correlation with metabolic diseases, including obesity and type 2 diabetes. Dysfunction of mitochondria results in detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, and thermogenesis, which consequently lead to metabolic diseases. Recent studies have shown that mitochondrial function can be improved by using thiazolidinedione, mitochondria-targeted antioxidants, and dietary natural compounds; by performing exercise; and by controlling caloric restriction, thereby maintaining the metabolic homeostasis by inducing adaptive thermogenesis of BAT and browning of WAT. In this review, we focus on and summarize the molecular regulation involved in the improvement of mitochondrial function in adipose tissues so that strategies can be developed to treat metabolic diseases.

Reduced lipogenesis in cafeteria-fed rats exhibiting diet-induced thermogenesis

1983 ◽  
Vol 3 (3) ◽  
pp. 217-224 ◽  
Author(s):  
Nancy J. Rothwell ◽  
Michael J. Stock ◽  
Paul Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Whole Body ◽  
Stock Diet ◽  
Inhibitory Effects ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

Fatty-acid synthesis has been measured in vivo with 3H2O in cafeteria-fed rats exhibiting diet-induced thermogenesis. Synthesis was decreased in brown adipose tissue, the liver, white adipose tissue, and the carcass of the cafeteria-fed animals compared to rats fed the normal stock diet. Whole-body synthesis was also decreased in the cafeteria-fed group. Diet-induced thermogenesis, in contrast to cold-induced non-shivering thermogenesis does not lead to increased fatty-acid synthesis and this is presumably due to the inhibitory effects on lipogenesis of the high dietary fat intake characteristic of cafeteria diets. The results also indicate that the energy cost of body fat deposition in cafeteria-fed rats is lower than in animals fed a low-fat/high-carbohydrate stock diet.

scholarly journals Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Craig Porter ◽  
Elisabet Børsheim ◽  
Labros S. Sidossis
Keyword(s):  
Adipose Tissue ◽  
Energy Metabolism ◽  
Brown Adipose Tissue ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Whole Body ◽  
Research Strategies ◽  
Brown Adipocytes ◽  
Brown Adipose

The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies.

scholarly journals Lactate Fluxes and Plasticity of Adipose Tissues: A Redox Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Damien Lagarde ◽  
Yannick Jeanson ◽  
Jean-Charles Portais ◽  
Anne Galinier ◽  
Isabelle Ader ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Biological Effects ◽  
Redox Homeostasis ◽  
Redox Balance ◽  
Whole Body ◽  
Glycolytic Flux ◽  
Adipose Tissues ◽  
Brown Adipose ◽  
Wide Range

Lactate, a metabolite produced when the glycolytic flux exceeds mitochondrial oxidative capacities, is now viewed as a critical regulator of metabolism by acting as both a carbon and electron carrier and a signaling molecule between cells and tissues. In recent years, increasing evidence report its key role in white, beige, and brown adipose tissue biology, and highlights new mechanisms by which lactate participates in the maintenance of whole-body energy homeostasis. Lactate displays a wide range of biological effects in adipose cells not only through its binding to the membrane receptor but also through its transport and the subsequent effect on intracellular metabolism notably on redox balance. This study explores how lactate regulates adipocyte metabolism and plasticity by balancing intracellular redox state and by regulating specific signaling pathways. We also emphasized the contribution of adipose tissues to the regulation of systemic lactate metabolism, their roles in redox homeostasis, and related putative physiopathological repercussions associated with their decline in metabolic diseases and aging.

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