scholarly journals Hyperleptinemia, Visceral Adiposity, and Decreased Glucose Tolerance in Mice with a Targeted Disruption of the Histidine Decarboxylase Gene

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4306-4314 ◽  
Author(s):  
András K. Fülöp ◽  
Anna Földes ◽  
Edit Buzás ◽  
Krisztina Hegyi ◽  
Ildikó H. Miklós ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Brown Adipose Tissue ◽  
Histidine Decarboxylase ◽  
Gene Knockout ◽  
Uncoupling Protein ◽  
Visceral Adiposity ◽  
Metabolic Phenotype ◽  
Targeted Disruption ◽  
Brown Adipose

Histamine has been referred to as an anorexic factor that decreases appetite and fat accumulation and affects feeding behavior. Tuberomammillary histaminergic neurons have been implicated in central mediation of peripheral metabolic signals such as leptin, and centrally released histamine inhibits ob gene expression. Here we have characterized the metabolic phenotype of mice that completely lack the ability to produce histamine because of targeted disruption of the key enzyme in histamine biosynthesis (histidine decarboxylase, HDC). Histochemical analyses confirmed the lack of HDC mRNA, histamine immunoreactivity, and histaminergic innervation throughout the brain of gene knockout mouse. Aged histamine-deficient (HDC−/−) mice are characterized by visceral adiposity, increased amount of brown adipose tissue, impaired glucose tolerance, hyperinsulinemia, and hyperleptinemia. Histamine-deficient animals are not hyperphagic but gain more weight and are calorically more efficient than wild-type controls. These metabolic changes presumably are due to the impaired regulatory loop between leptin and hypothalamic histamine that results in orexigenic dominance through decreased energy expenditure, attenuated ability to induce uncoupling protein-1 mRNA in the brown adipose tissue and defect in mobilizing energy stores. Our results further support the role of histamine in regulation of energy homeostasis.

scholarly journals A single mutation in uncoupling protein of rat brown adipose tissue mitochondria abolishes GDP sensitivity of H+ transport.

1994 ◽  
Vol 269 (10) ◽  
pp. 7435-7438
Author(s):  
D.L. Murdza-Inglis ◽  
M. Modriansky ◽  
H.V. Patel ◽  
G. Woldegiorgis ◽  
K.B. Freeman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Single Mutation ◽  
Brown Adipose

scholarly journals TAF7L modulates brown adipose tissue formation

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haiying Zhou ◽  
Bo Wan ◽  
Ivan Grubisic ◽  
Tommy Kaplan ◽  
Robert Tjian
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Core Promoter ◽  
Uncoupling Protein ◽  
Dna Looping ◽  
Chromatin Interactions ◽  
Brown Adipose ◽  
Important Regulator

Brown adipose tissue (BAT) plays an essential role in metabolic homeostasis by dissipating energy via thermogenesis through uncoupling protein 1 (UCP1). Previously, we reported that the TATA-binding protein associated factor 7L (TAF7L) is an important regulator of white adipose tissue (WAT) differentiation. In this study, we show that TAF7L also serves as a molecular switch between brown fat and muscle lineages in vivo and in vitro. In adipose tissue, TAF7L-containing TFIID complexes associate with PPARγ to mediate DNA looping between distal enhancers and core promoter elements. Our findings suggest that the presence of the tissue-specific TAF7L subunit in TFIID functions to promote long-range chromatin interactions during BAT lineage specification.

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.

Corticosterone decreases nonshivering thermogenesis and increases lipid storage in brown adipose tissue

1995 ◽  
Vol 268 (1) ◽  
pp. R183-R191 ◽  
Author(s):  
A. M. Strack ◽  
M. J. Bradbury ◽  
M. F. Dallman
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucocorticoid Receptors ◽  
Uncoupling Protein ◽  
Lipid Storage ◽  
Scatchard Analysis ◽  
Nonshivering Thermogenesis ◽  
Diurnal Range ◽  
Brown Adipose ◽  
Intact Rats

Brown adipose tissue (BAT) contains glucocorticoid receptors; glucocorticoids are required for maintaining differentiated BAT in culture. These studies were performed to determine the effects of corticosterone on BAT thermogenic function and lipid storage. Rats were adrenalectomized and given subcutaneous corticosterone pellets in concentrations that maintained plasma corticosterone constant across the range of 0-20 micrograms/dl or were sham adrenalectomized. All variables were examined 5 days after surgery and corticosterone replacement. Measures of BAT function-thermogenic capacity [guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP; a BAT-specific thermogenic protein)] and storage (BAT wet wt, protein, and DNA levels) were made. Plasma hormones (corticosterone, adrenocorticotropic hormone, insulin, 3,3',5-triiodothyronine, and thyroxine were measured. Corticosterone significantly affected BAT thermogenic measures: UCP content and binding of GDP to BAT mitochondria decreased with increasing corticosterone; GDP binding characteristics in BAT from similarly prepared rats examined by Scatchard analysis showed that maximum binding (Bmax) and dissociation constant (Kd) decreased with increasing corticosterone dose. BAT DNA was increased by adrenalectomy and maintained at intact levels with all doses of corticosterone; BAT lipid storage increased dramatically at corticosterone values higher than the daily mean level in intact rats. Histologically, the number and size of lipid droplets within BAT adipocytes increased markedly with increased corticosterone. White adipose depots were more sensitive to circulating corticosterone concentrations than were BAT depots and increased in weight at levels of corticosterone that were at or below the daily mean level of intact rats. We conclude that, within its diurnal range of concentration corticosterone acts to inhibit nonshivering thermogenesis and increase lipid storage.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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