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 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.

Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPδ

2012 ◽  
Vol 443 (3) ◽  
pp. 799-810 ◽  
Author(s):  
Jordi Armengol ◽  
Josep A. Villena ◽  
Elayne Hondares ◽  
María C. Carmona ◽  
Hei Sook Sul ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Proximal Promoter ◽  
Brown Adipocyte ◽  
Specific Marker ◽  
Brown Adipose ◽  
Factor C

Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) α-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPδ activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPδ knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPδ in C/EBPα-null BAT and high expression of C/EBPδ in brown pre-adipocytes. Dexamethasone treatment of brown pre-adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPδ and strongly impaired expression of the thermogenic markers UCP1 and PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-α]. However, it did not alter normal fat accumulation or expression of non-BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPδ as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation.

scholarly journals Physical Activity Attenuates the Obesity-Induced Dysregulated Expression of Brown Adipokines in Murine Interscapular Brown Adipose Tissue

2021 ◽  
Vol 22 (19) ◽  
pp. 10391
Author(s):  
Takuya Sakurai ◽  
Toshiyuki Fukutomi ◽  
Sachiko Yamamoto ◽  
Eriko Nozaki ◽  
Takako Kizaki
Keyword(s):  
Physical Activity ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Focal Point ◽  
Brown Adipocyte ◽  
Obese Mice ◽  
Gene Expressions ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

In recent years, brown adipose tissue (BAT), which has a high heat-producing capacity, has been confirmed to exist even in adults, and it has become a focal point for the prevention and the improvement of obesity and lifestyle-related diseases. However, the influences of obesity and physical activity (PA) on the fluid factors secreted from BAT (brown adipokines) are not well understood. In this study, therefore, we focused on brown adipokines and investigated the effects of obesity and PA. The abnormal expressions of gene fluid factors such as galectin-3 (Lgals3) and Lgals3 binding protein (Lgals3bp), whose proteins are secreted from HB2 brown adipocytes, were observed in the interscapular BAT of obese mice fed a high-fat diet for 4 months. PA attenuated the abnormalities in the expressions of these genes. Furthermore, although the gene expressions of factors related to brown adipocyte differentiation such as peroxisome proliferator-activated receptor gamma coactivator 1-α were also down-regulated in the BAT of the obese mice, PA suppressed the down-regulation of these factors. On the other hand, lipogenesis was increased more in HB2 cells overexpressing Lgals3 compared with that in control cells, and the overexpression of Lgals3bp decreased the mitochondrial mass. These results indicate that PA attenuates the obesity-induced dysregulated expression of brown adipokines and suggests that Lgals3 and Lgals3bp are involved in brown adipocyte differentiation.

scholarly journals Regulation of mitochondrial biogenesis in brown adipose tissue: nuclear respiratory factor-2/GA-binding protein is responsible for the transcriptional regulation of the gene for the mitochondrial ATP synthase β subunit

1998 ◽  
Vol 331 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Josep A. VILLENA ◽  
Octavi VIÑAS ◽  
Teresa MAMPEL ◽  
Roser IGLESIAS ◽  
Marta GIRALT ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Adipocyte Differentiation ◽  
Brown Adipocyte ◽  
Brown Adipocytes ◽  
Nuclear Respiratory Factor ◽  
Brown Adipose ◽  
Nuclear Respiratory Factor 2 ◽  
Ga Binding Protein

The regulation of transcription of the gene for the β subunit of the FoF1 ATP synthase (ATPsynβ) in brown adipose tissue has been studied as a model to determine the molecular mechanisms for mitochondrial biogenesis associated with brown adipocyte differentiation. The expression of the ATPsynβ mRNA is induced during the brown adipocyte differentiation that occurs during murine prenatal development or when brown adipocytes differentiate in culture. This induction occurs in parallel with enhanced gene expression for other nuclear and mitochondrially-encoded components of the respiratory chain/oxidative phosphorylation system (OXPHOS). Transient transfection assays indicated that the expression of the ATPsynβ gene promoter is higher in differentiated HIB-1B brown adipocytes than in non-differentiated HIB-1B cells. A major transcriptional regulatory site was identified between nt -306 and -266 in the ATPsynβ promoter. This element has a higher enhancer capacity in differentiated brown adipocyte HIB-1B cells than in non-differentiated cells. Electrophoretic shift analysis indicated that Sp1and nuclear respiratory factor-2/GA-binding protein (NRF2/GABP) were the main nuclear proteins present in brown adipose tissue that bind this site. Double-point mutant analysis indicated a major role for the NRF2/GABP site in the enhancer capacity of this element in brown fat cells. It is proposed that NRF2/GABP plays a pivotal role in the co-ordinated enhancement of OXPHOS gene expression associated with mitochondrial biogenesis in brown adipocyte differentiation.

scholarly journals Berardinelli-Seip Congenital Lipodystrophy 2/Seipin Is Not Required for Brown Adipogenesis but Regulates Brown Adipose Tissue Development and Function

2016 ◽  
Vol 36 (15) ◽  
pp. 2027-2038 ◽  
Author(s):  
Hongyi Zhou ◽  
Stephen M. Black ◽  
Tyler W. Benson ◽  
Neal L. Weintraub ◽  
Weiqin Chen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Endoplasmic Reticulum Membrane ◽  
Brown Adipocytes ◽  
White Adipocyte ◽  
Brown Adipose ◽  
And Function

Brown adipose tissue (BAT) plays a unique role in regulating whole-body energy homeostasis by dissipating energy through thermogenic uncoupling. Berardinelli-Seip congenital lipodystrophy (BSCL) type 2 (BSCL2; also known as seipin) is a lipodystrophy-associated endoplasmic reticulum membrane protein essential for white adipocyte differentiation. Whether BSCL2 directly participates in brown adipocyte differentiation, development, and function, however, is unknown. We show that BSCL2 expression is increased during brown adipocyte differentiation. Its deletion does not impair the classic brown adipogenic program but rather induces premature activation of differentiating brown adipocytes through cyclic AMP (cAMP)/protein kinase A (PKA)-mediated lipolysis and fatty acid and glucose oxidation, as well as uncoupling. cAMP/PKA signaling is physiologically activated during neonatal BAT development in wild-type mice and greatly potentiated in mice with genetic deletion ofBscl2in brown progenitor cells, leading to reduced BAT mass and lipid content during neonatal brown fat formation. However, prolonged overactivation of cAMP/PKA signaling during BAT development ultimately causes apoptosis of brown adipocytes through inflammation, resulting in BAT atrophy and increased overall adiposity in adult mice. These findings reveal a key cell-autonomous role for BSCL2 in controlling BAT mass/activity and provide novel insights into therapeutic strategies targeting cAMP/PKA signaling to regulate brown adipocyte function, viability, and metabolic homeostasis.

Abstract 041: mTORC1 is Required for Leptin-induced Sympathetic Activation to the Kidney but Not Brown Adipose Tissue

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Balyssa B Bell ◽  
Donald A Morgan ◽  
Kamal Rahmouni
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Molecular Mechanisms ◽  
Leptin Receptor ◽  
Critical Role ◽  
Conditional Knockout ◽  
Sympathetic Activation ◽  
Long Term Effects ◽  
Brown Adipose ◽  
Mtorc1 Signaling

The adipocyte-derived hormone leptin plays a critical role in the regulation of energy homeostasis through its action in the brain to decrease food intake and promote energy expenditure by increasing sympathetic nerve activity (SNA) to the thermogenic brown adipose tissue (BAT). Leptin also increases SNA to cardiovascular organs including the kidney and raises arterial pressure. However, it is unclear whether leptin controls regional SNA via conserved or distinct molecular mechanisms. Multiple intracellular pathways have been associated with leptin signaling including the mechanistic target of rapamycin complex 1 (mTORC1), which has been proposed as a critical determinant of leptin action. Here, we assessed the contribution of mTORC1 signaling to leptin-evoked regional sympathetic activation. Simultaneous multifiber recording of renal and BAT SNA in anesthetized C57BL/6J mice showed that intracerebroventricular (ICV) administration of leptin (2μg, n=5) increased both renal (170±34%) and BAT (208±37%) SNA. Interestingly, ICV pre-treatment with the mTORC1 inhibitor (rapamycin, 5ng, n=6) abolished the leptin-induced increase in renal (10±6%, P<0.05 vs controls) but not BAT (226±31%) SNA. Next, we used conditional knockout mice that lack the critical mTORC1 subunit, Raptor, specifically in leptin receptor (LRb)-expressing cells (LRb Cre /Raptor fl/fl ) to determine the long-term effects of disrupting mTORC1 signaling on leptin-evoked increase in regional SNA. We confirmed the inability of leptin to activate mTORC1 signaling in LRb-expressing cells of LRb Cre /Raptor fl/fl mice relative to controls using immunohistochemical staining of phosphorylated ribosomal S6, a downstream target of mTORC1. We observed a significant increase in renal SNA in response to ICV leptin in control mice (127±16%, n=9), but not in LRb Cre /Raptor fl/fl mice (-4±15%, n=9, P<0.05 vs controls). Conversely, ICV leptin-induced increase in BAT SNA was not different in LRb Cre /Raptor fl/fl mice (109±27%, n=5) vs. littermate controls (173±52%, n=4). Our data suggest a critical role for mTORC1 signaling in selectively mediating the cardiovascular sympathetic but not the thermogenic actions of leptin, with important implications for obesity-associated hypertension.

KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch Signaling

2021 ◽  
Author(s):  
Mingsheng Ye ◽  
Liping Luo ◽  
Qi Guo ◽  
Guanghua Lei ◽  
Chao Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Notch Signaling ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Notch Signaling Pathway ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Metabolic Function ◽  
Brown Adipose

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

CNS origins of the sympathetic nervous system outflow to brown adipose tissue

1999 ◽  
Vol 276 (6) ◽  
pp. R1569-R1578 ◽  
Author(s):  
Maryam Bamshad ◽  
C. Kay Song ◽  
Timothy J. Bartness
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Sympathetic Nervous System ◽  
Brown Adipose Tissue ◽  
Pseudorabies Virus ◽  
Critical Role ◽  
Hypothalamic Nucleus ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Diet Induced Thermogenesis

Brown adipose tissue (BAT) plays a critical role in cold- and diet-induced thermogenesis. Although BAT is densely innervated by the sympathetic nervous system (SNS), little is known about the central nervous system (CNS) origins of this innervation. The purpose of the present experiment was to determine the neuroanatomic chain of functionally connected neurons from the CNS to BAT. A transneuronal viral tract tracer, Bartha’s K strain of the pseudorabies virus (PRV), was injected into the interscapular BAT of Siberian hamsters. The animals were killed 4 and 6 days postinjection, and the infected neurons were visualized by immunocytochemistry. PRV-infected neurons were found in the spinal cord, brain stem, midbrain, and forebrain. The intensity of labeled neurons in the forebrain varied from heavy infections in the medial preoptic area and paraventricular hypothalamic nucleus to few infections in the ventromedial hypothalamic nucleus, with moderate infections in the suprachiasmatic and lateral hypothalamic nuclei. These results define the SNS outflow from the brain to BAT for the first time in any species.

scholarly journals GPR120 controls neonatal brown adipose tissue thermogenic induction

2019 ◽  
Vol 317 (5) ◽  
pp. E742-E750 ◽  
Author(s):  
Tania Quesada-López ◽  
Aleix Gavaldà-Navarro ◽  
Samantha Morón-Ros ◽  
Laura Campderrós ◽  
Roser Iglesias ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Receptor Protein ◽  
Brown Adipocyte ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
G Protein Coupled

Adaptive induction of thermogenesis in brown adipose tissue (BAT) is essential for the survival of mammals after birth. We show here that G protein-coupled receptor protein 120 (GPR120) expression is dramatically induced after birth in mouse BAT. GPR120 expression in neonatal BAT is the highest among GPR120-expressing tissues in the mouse at any developmental stage tested. The induction of GPR120 in neonatal BAT is caused by postnatal thermal stress rather than by the initiation of suckling. GPR120-null neonates were found to be relatively intolerant to cold: close to one-third did not survive at 21°C, but all such pups survived at 25°C. Heat production in BAT was significantly impaired in GPR120-null pups. Deficiency in GPR120 did not modify brown adipocyte morphology or the anatomical architecture of BAT, as assessed by electron microscopy, but instead impaired the expression of uncoupling protein-1 and the fatty acid oxidation capacity of neonatal BAT. Moreover, GPR120 deficiency impaired fibroblast growth factor 21 (FGF21) gene expression in BAT and reduced plasma FGF21 levels. These results indicate that GPR120 is essential for neonatal adaptive thermogenesis.

Control of brown adipose tissue lipolysis and respiration by adenosine

1983 ◽  
Vol 245 (6) ◽  
pp. E555-E559 ◽  
Author(s):  
D. Szillat ◽  
L. J. Bukowiecki
Keyword(s):  
Adipose Tissue ◽  
Cyclic Amp ◽  
Palmitic Acid ◽  
Brown Adipose Tissue ◽  
Brown Adipocyte ◽  
Tissue Respiration ◽  
Dibutyryl Cyclic Amp ◽  
Response Curves ◽  
Brown Adipose ◽  
Stimulation Of

Adenosine competitively inhibited the stimulatory effects of (-)-isoproterenol on lipolysis and respiration in hamster brown adipocytes. The low value of the apparent ki for respiratory inhibition by adenosine (7 nM) indicated that the nucleoside may control brown adipocyte function under physiological concentrations. Significantly, the dose-response curves for isoproterenol stimulation of lipolysis and respiration were both shifted by adenosine to higher agonist concentrations by the same order of magnitude, providing additional evidence for a tight coupling between lipolysis and respiration. The inhibitory effects of adenosine were rapidly reversed by a) adenosine deaminase, b) agents known to increase intracellular cyclic AMP levels (isoproterenol, isobutylmethylxanthine, dibutyryl cyclic AMP), and c) direct stimulation of respiration with palmitic acid. These results, combined with the fact that adenosine failed to affect respiration evoked either by dibutyryl cyclic AMP or by palmitic acid, strongly indicate that adenosine regulates brown adipose tissue respiration at an early metabolic step of the stimulus-thermogenesis sequence, most probably at the level of the adenylate cyclase complex.

Sign in / Sign up

Export Citation Format

Share Document