Brown adipose tissue whitening leads to brown adipocyte death and adipose tissue inflammation

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.

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GPR120 controls neonatal brown adipose tissue thermogenic induction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00081.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. E742-E750 ◽

Cited By ~ 2

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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Control of brown adipose tissue lipolysis and respiration by adenosine

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.245.6.e555 ◽

1983 ◽

Vol 245 (6) ◽

pp. E555-E559 ◽

Cited By ~ 1

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.

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