3.Research advances in the origin and formation of brown adipose.
Acta Academiae Medicinae Sinicae 2009;31(6):778-781
Brown adipose tissue contributes to energy balance in humans by generating heat via the mitochondrial uncoupling of lipid oxidation. Currently it is believed that brown adipose has two origins: Myf5-negative progenitor (its source is same as that of white adipocyte) and Myf5-positive progenitor (its source is same as myocyte). Due to the different origins of brown adipocytes, they may be formed via multiple pathways which include the main pathway (by which Myf5-positive progenitors differentiate into brown adipocytes that distribute in classical locations) and alternative pathway (by which Myf5-negative progenitors differentiate into brown adipocytes that distribute in white adipose tissue).
Adipocytes
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cytology
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Adipose Tissue, Brown
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cytology
;
physiology
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Humans
4.Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions
Tae Heung KANG ; Jung Hwa PARK ; Donghyeok SHIN ; Hyungon CHOI ; Jeenam KIM ; Myung Chul LEE
Tissue Engineering and Regenerative Medicine 2019;16(5):539-548
BACKGROUND: Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (T(reg)) expression under intermittent hypobaric conditions. METHODS: Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of T(regs) (CD4 + CD25 + Foxp3 + T cells), cytokines [tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined. RESULTS: Splenocytes, cultured with brown and white adipocytes, exhibited comparable T(reg) expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of T(regs). However, a decrease in T(regs) was found in the white adipocyte group. TNF-α levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions. CONCLUSION: Both brown and white adipocytes support T(reg) expression when they are cultured with splenocytes. Of note, brown adipocytes maintained T(reg) expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.
Adipocytes
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Adipocytes, Brown
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Adipocytes, White
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Animals
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Coculture Techniques
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Cytokines
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Humans
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Infant, Newborn
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Interleukin-10
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Ligands
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Mice
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Necrosis
5.Recent advance in brown adipose physiology and its therapeutic potential.
Yun Hee LEE ; Young Suk JUNG ; Dalwoong CHOI
Experimental & Molecular Medicine 2014;46(2):e78-
Brown adipose tissue (BAT) is a specialized thermoregulatory organ that has a critical role in the regulation of energy metabolism. Specifically, energy expenditure can be enhanced by the activation of BAT function and the induction of a BAT-like catabolic phenotype in white adipose tissue (WAT). Since the recent recognition of metabolically active BAT in adult humans, BAT has been extensively studied as one of the most promising targets identified for treating obesity and its related disorders. In this review, we summarize information on the developmental origin of BAT and the progenitors of brown adipocytes in WAT. We explore the transcriptional control of brown adipocyte differentiation during classical BAT development and in WAT browning. We also discuss the neuronal control of BAT activity and summarize the recently identified non-canonical stimulators of BAT that can act independently of beta-adrenergic stimulation. Finally, we review new findings on the beneficial effects of BAT activation and development with respect to improving metabolic profiles. We highlight the therapeutic potential of BAT and its future prospects, including pharmacological intervention and cell-based therapies designed to enhance BAT activity and development.
Adipocytes/cytology/metabolism
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Adipogenesis
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Adipose Tissue, Brown/cytology/metabolism/*physiology
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Animals
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Humans
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Obesity/therapy
6.Food Intake and Thermogenesis in Adipose Tissue
Tsuyoshi GOTO ; Minji KIM ; Haruya TAKAHASHI ; Nobuyuki TAKAHASHI ; Teruo KAWADA
Korean Journal of Obesity 2016;25(3):109-114
Brown adipose tissue (BAT) is regarded as a key target for developing interventions to prevent and treat obesity and age-related diseases. In addition, uncoupling pro tein 1 (UCP1)
Adipocytes
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Adipose Tissue
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Adipose Tissue, Brown
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Adipose Tissue, White
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Atrophy
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Eating
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Humans
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Middle Aged
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Obesity
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Thermogenesis
7.The dark side of browning.
Kirstin A TAMUCCI ; Maria NAMWANJE ; Lihong FAN ; Li QIANG
Protein & Cell 2018;9(2):152-163
The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning. This review aims to highlight the adverse outcomes of both overactive and underactive browning activity, the harmful side effects of browning agents, as well as the molecular brake-switch system that has been proposed to regulate this process. Developing novel strategies that both sustain the metabolic improvements of WAT browning and attenuate the related adverse side effects is therefore essential for unlocking the therapeutic potential of browning agents in the treatment of metabolic diseases.
Adipocytes, Beige
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cytology
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Adipose Tissue, Brown
;
cytology
;
metabolism
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Adipose Tissue, White
;
cytology
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Aging
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metabolism
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Animals
;
Humans
8.Imprint Cytology of Hibernoma: A Case Report.
Joon Hyuk CHOI ; Duk Seop SHIN
Korean Journal of Cytopathology 2008;19(2):200-205
Hibernoma is a rare, benign adipose tumor composed of brown fat cells with eosinophilic granular or multivacuolated cytoplasm. The cytologic features of hibernoma have been rarely reported and may mimic other polygonal cell neoplasms. We report the imprint cytologic features of a case of hibernoma in the left thigh of a 68-year-old woman. Microscopic examination showed large, round, or polygonal brown fat cells. The cells were arranged in fragments or clusters. The nuclei were uniformly round with finely granular chromatin. The cytoplasm was multivacuolated or univacuolated. The abundant eosinophilic granular cytoplasm was also present. No nuclear atypia were present. Immunohistochemical staining showed that cells were positive for S-100 protein.
Adipocytes, Brown
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Aged
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Chromatin
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Cytoplasm
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Eosinophils
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Female
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Humans
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Hydrazines
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Lipoma
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S100 Proteins
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Thigh
9.Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation
Eun Kyung KIM ; Seung Hoon LEE ; Seon Young LEE ; Jae kyung KIM ; Joo Yeon JHUN ; Hyun Sik NA ; Se Young KIM ; Jong Young CHOI ; Chul Woo YANG ; Sung Hwan PARK ; Mi La CHO
Experimental & Molecular Medicine 2018;50(1):e432-
Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive inflammation. Recently, RA associated with a metabolic disorder was revealed to be non-responsive to RA medications. Metformin has been reported to have a therapeutic effect on RA and obesity. The aim of this investigation was to study the therapeutic effect and the underlying mechanism of metformin's action in an experimental model of collagen-induced arthritis (CIA) associated with obesity. Metformin was administered daily for 13 weeks to mice with CIA that had been fed a high-fat diet. Metformin ameliorated the development of CIA in obese mice by reducing autoantibody expression and joint inflammation. Furthermore, metformin decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing effect on the metabolic profile of obese CIA mice. In addition, metformin increased the production of pAMPK and FGF21. Metformin also induced the differentiation of brown adipose tissue (BAT), which led to a reciprocal balance between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo. These results suggest that metformin can dampen the development of CIA in obese mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus, metformin could be a therapeutic candidate for non-responsive RA.
Adipocytes, Brown
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Adipose Tissue, Brown
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Animals
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Arthritis
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Arthritis, Experimental
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Arthritis, Rheumatoid
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Autoimmune Diseases
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Diet, High-Fat
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In Vitro Techniques
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Inflammation
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Joints
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Metabolome
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Metformin
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Mice
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Mice, Obese
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Models, Theoretical
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Obesity
10.Brown Fat and Browning for the Treatment of Obesity and Related Metabolic Disorders.
Diabetes & Metabolism Journal 2016;40(1):12-21
Brown fat is a specialized fat depot that can increase energy expenditure and produce heat. After the recent discovery of the presence of active brown fat in human adults and novel transcription factors controlling brown adipocyte differentiation, the field of the study of brown fat has gained great interest and is rapidly growing. Brown fat expansion and/or activation results in increased energy expenditure and a negative energy balance in mice and limits weight gain. Brown fat is also able to utilize blood glucose and lipid and results in improved glucose metabolism and blood lipid independent of weight loss. Prolonged cold exposure and beta adrenergic agonists can induce browning of white adipose tissue. The inducible brown adipocyte, beige adipocyte evolving by thermogenic activation of white adipose tissue have different origin and molecular signature from classical brown adipocytes but share the characteristics of high mitochondria content, UCP1 expression and thermogenic capacity when activated. Increasing browning may also be an efficient way to increase whole brown fat activity. Recent human studies have shown possibilities that findings in mice can be reproduced in human, making brown fat a good candidate organ to treat obesity and its related disorders.
Adipocytes
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Adipocytes, Brown
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Adipose Tissue, Brown*
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Adipose Tissue, White
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Adrenergic beta-Agonists
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Adult
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Animals
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Blood Glucose
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Energy Metabolism
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Glucose
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Hot Temperature
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Humans
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Metabolism
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Mice
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Mitochondria
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Obesity*
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Transcription Factors
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Weight Gain
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Weight Loss