scholarly journals Loss of FSTL1-expressing adipocyte progenitors drives the age-related involution of brown adipose tissue

2020 ◽  
Author(s):  
Zan Huang ◽  
Zengdi Zhang ◽  
Ryan Heck ◽  
Ping Hu ◽  
Hezkiel Nanda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Stromal Vascular Fraction ◽  
Brown Adipocyte ◽  
List Type ◽  
Cellular Mechanisms ◽  
Age Related ◽  
Brown Adipose ◽  
Adipocyte Progenitors ◽  
Genetic Deletion

SUMMARYIn humans, brown adipose tissue (BAT) undergoes progressive involution or atrophy with increasing age, as manifested by decreased prevalence and mass, transformation to white adipose tissue (WAT), and reduction in thermogenic activity. This involution process cannot be fully recapitulated in rodent models and thus underlying cellular mechanisms are poorly understood. Here, we show that the interscapular BAT (iBAT) in rabbits involutes rapidly in early life, similarly to that in humans. The transcriptomic remodeling and identity switch of mature adipocytes are accompanied with the loss of brown adipogenic competence of their precursor cells. Through single-cell RNA sequencing, we surveyed the heterogenous populations of mesenchymal cells within the stromal vascular fraction of rabbit and human iBAT. An analogous FSTL1high population of brown adipocyte progenitors exists in both species while gradually disappear during iBAT involution in rabbits. In mice, FSTL1 is highly expressed by adipocyte progenitors in iBAT and genetic deletion of FSTL1 causes defective WNT signaling and iBAT atrophy in neonates. Our results underscore the BAT-intrinsic contribution from FSTL1high progenitors to age-related tissue involution and point to a potential therapeutic approach for obesity and its comorbidities.HIGHLIGHTSRabbit BAT irreversibly transforms to WAT before puberty.iBAT adipocyte progenitors reprogram transcriptome and lose brown adipogenic ability.Comparable FSTL1high brown adipocyte progenitors exist in rabbit and human iBAT.Loss of FSTL1 in brown adipocyte progenitors causes iBAT atrophy in mice.

scholarly journals Orexin Restores Aging-Related Brown Adipose Tissue Dysfunction in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (2) ◽  
pp. 485-501 ◽  
Author(s):  
Dyan Sellayah ◽  
Devanjan Sikder
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Fat Mass ◽  
Core Body Temperature ◽  
Brown Adipocyte ◽  
Aged Mice ◽  
Age Related ◽  
Brown Adipose ◽  
The Impact

The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.

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.

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.

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

2018 ◽  
Vol 59 (5) ◽  
pp. 784-794 ◽  
Author(s):  
Petra Kotzbeck ◽  
Antonio Giordano ◽  
Eleonora Mondini ◽  
Incoronata Murano ◽  
Ilenia Severi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Adipocyte ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Brown Adipose

scholarly journals Angiotensin 1–7 stimulates brown adipose tissue and reduces diet-induced obesity

2018 ◽  
Vol 314 (2) ◽  
pp. E131-E138 ◽  
Author(s):  
Hidechika Morimoto ◽  
Jun Mori ◽  
Hisakazu Nakajima ◽  
Yasuhiro Kawabe ◽  
Yusuke Tsuma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Renin Angiotensin System ◽  
Hormone Sensitive Lipase ◽  
Brown Adipocyte ◽  
Metabolic Complications ◽  
Subcutaneous White Adipose Tissue ◽  
Beneficial Effects ◽  
Diet Induced Obesity ◽  
Brown Adipose

The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1–7 (Ang 1–7) peptide. We hypothesized that the antiobesity effect of Ang 1–7 was related to the stimulation of brown adipose tissue (BAT). We administered Ang 1–7 (0.54 mg kg−1 day−1) for 28 days via implanted micro-osmotic pumps to mice with high-fat diet (HFD)-induced obesity. Ang 1–7 treatment reduced body weight, upregulated thermogenesis, and ameliorated impaired glucose homeostasis without affecting food consumption. Furthermore, Ang 1–7 treatment enlarged BAT and the increased expression of UCP1, PRDM16, and prohibitin. Alterations in PRDM16 expression correlated with increased AMPK and phosphorylation of mTOR. Ang 1–7 treatment elevated thermogenesis in subcutaneous white adipose tissue without altering UCP1 expression. These changes occurred in the context of decreased lipid accumulation in BAT from HFD-fed mice, preserved insulin signaling concomitant with phosphorylation of hormone-sensitive lipase and decreased expression of perilipin. These data suggest that Ang 1–7 induces brown adipocyte differentiation leading to upregulation of thermogenesis and improved metabolic profile in diet-induced obesity. Enhancing Ang 1–7 action represents a promising therapy to increase BAT and to reduce the metabolic complications associated with diet-induced obesity.

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