scholarly journals Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat

2010 ◽  
Vol 108 (1) ◽  
pp. 143-148 ◽  
Author(s):  
Tim J. Schulz ◽  
Tian Lian Huang ◽  
Thien T. Tran ◽  
Hongbin Zhang ◽  
Kristy L. Townsend ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cell Fate ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Molecular Characteristics ◽  
Fat Cell ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
White Fat

Brown fat is specialized for energy expenditure and has therefore been proposed to function as a defense against obesity. Despite recent advances in delineating the transcriptional regulation of brown adipocyte differentiation, cellular lineage specification and developmental cues specifying brown-fat cell fate remain poorly understood. In this study, we identify and isolate a subpopulation of adipogenic progenitors (Sca-1+/CD45−/Mac1−; referred to as Sca-1+ progenitor cells, ScaPCs) residing in murine brown fat, white fat, and skeletal muscle. ScaPCs derived from different tissues possess unique molecular expression signatures and adipogenic capacities. Importantly, although the ScaPCs from interscapular brown adipose tissue (BAT) are constitutively committed brown-fat progenitors, Sca-1+ cells from skeletal muscle and subcutaneous white fat are highly inducible to differentiate into brown-like adipocytes upon stimulation with bone morphogenetic protein 7 (BMP7). Consistent with these findings, human preadipocytes isolated from subcutaneous white fat also exhibit the greatest inducible capacity to become brown adipocytes compared with cells isolated from mesenteric or omental white fat. When muscle-resident ScaPCs are re-engrafted into skeletal muscle of syngeneic mice, BMP7-treated ScaPCs efficiently develop into adipose tissue with brown fat-specific characteristics. Importantly, ScaPCs from obesity-resistant mice exhibit markedly higher thermogenic capacity compared with cells isolated from obesity-prone mice. These data establish the molecular characteristics of tissue-resident adipose progenitors and demonstrate a dynamic interplay between these progenitors and inductive signals that act in concert to specify brown adipocyte development.

Abstract 339: Impaired Periaortic Adipocyte Differentiation in Angiotensin AT1 Receptor-Deficient Mice: Possible Role in Proinflammatory Phenotypic Modulation of Perivascular Adipose Tissue

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Daisuke Irie ◽  
Hiroyuki Yamada ◽  
Taku Kato ◽  
Hiroyuki Kawahito ◽  
Kouji Ikeda ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
At1 Receptor ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Interscapular Brown Adipose Tissue ◽  
Perivascular Adipose Tissue ◽  
Expression Levels ◽  
Brown Adipose ◽  
Differentiation Marker

[BACKGROUND] The angiotensin II type 1 (AT1) receptor in visceral white adipose tissue (WAT) is closely implicated in lipid metabolism and energy homeostasis. Recently, perivascular adipose tissue (PVAT) has been shown to play a crucial role in the development of atherosclerosis; however, the effects of AT1 on PVAT properties and their functional relevance in atherogenesis remain undefined. [METHOD AND RESULT] We examined the fat depot-specific difference of adipose tissue among epididymal WAT, PVAT surrounding thoracic aorta, and interscapular brown adipose tissue (BAT) in 8-week-old apoE deficient (apoE-/-) mice. The expression levels of brown adipocyte marker genes (UCP-1, PGC-1α, Elovl3, PPARα, and Cidea) were significantly higher in BAT and PVAT compared with WAT (P<0.01). White adipocyte marker genes (Igfbp3, DPT, Tcf21, and Hoxc9), which were hardly expressed in BAT, showed a moderate expression levels in PVAT, suggesting that PVAT has a strikingly different phenotype from the classical WAT and BAT. We next examined the properties of PVAT in 8-week-old apoE-/-/AT1 receptor deficient (Agtr1-/-) mice. After 4 weeks of western diet, the expression levels of adipocyte differentiation maker genes (PPARγ, FABP4, c/EBPα) were markedly increased in apoE -/- PVAT (P<0.05), which was completely diminished in apoE-/-/Agtr1 -/- PVAT (P<0.01). To investigate the effect of AT1 on the periaortic adipocyte differentiation, we performed primary culture of preadipocyte from stromal vascular fraction in Agtr1 -/- and Agtr1+/+ PVAT. The mRNA expressions of adipocyte differentiation marker genes (PPARγ, FABP4, and c/EBPα) were time-dependently increased in Agtr1+/+ adipocyte. In contrast, FABP4 and c/EBPα mRNA expressions were markedly inhibited in Agtr1 -/- adipocyte, whereas PPARγ did not differ between the two groups during differentiation, suggesting that AT1 is essentially implicated in the terminal differentiation of periaortic adipocyte. [CONCLUSION] Our findings demonstrate that AT1 regulates the expression levels of late stage of adipocyte-differentiation marker genes in PVAT, suggesting that AT1-mediated modulation of periaortic adipocyte differentiation could be a novel therapeutic target for the prevention of atherosclerosis.

Diet, lighting, and food intake affect norepinephrine turnover in dietary obesity

1987 ◽  
Vol 252 (2) ◽  
pp. R402-R408 ◽  
Author(s):  
T. Yoshida ◽  
J. S. Fisler ◽  
M. Fukushima ◽  
G. A. Bray ◽  
R. A. Schemmel
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Brown Fat ◽  
Light Cycle ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Dietary Obesity

The effects of dietary fat content, lighting cycle, and feeding time on norepinephrine turnover in interscapular brown adipose tissue, heart, and pancreas, and on blood 3-hydroxybutyrate, serum glucose, insulin, and corticosterone have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to dietary obesity, have a more rapid turnover of norepinephrine in interscapular brown adipose tissue and heart and a greater increase in the concentration of norepinephrine in brown fat when eating a high-fat diet than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. Light cycle and feeding schedule are important modulators of sympathetic activity in heart and pancreas but not in brown fat. Rats of the resistant strain also have higher blood 3-hydroxybutyrate concentrations and lower insulin and corticosterone levels than do rats of the susceptible strain. A high-fat diet increases 3-hydroxybutyrate concentrations and reduces insulin levels in both strains. These studies show, in rats eating a high-fat diet, that differences in norepinephrine turnover, particularly in brown adipose tissue, may play an important role in whether dietary obesity develops and in the manifestations of resistance to this phenomenon observed in the S 5B/Pl rat.

scholarly journals HOXA5 Participates in Brown Adipose Tissue and Epaxial Skeletal Muscle Patterning and in Brown Adipocyte Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Miriam A. Holzman ◽  
Abigail Ryckman ◽  
Tova M. Finkelstein ◽  
Kim Landry-Truchon ◽  
Kyra A. Schindler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Muscle Development ◽  
Lineage Tracing ◽  
Brown Adipocyte ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Droplet Morphology ◽  
Epaxial Muscle

Brown adipose tissue (BAT) plays critical thermogenic, metabolic and endocrine roles in mammals, and aberrant BAT function is associated with metabolic disorders including obesity and diabetes. The major BAT depots are clustered at the neck and forelimb levels, and arise largely within the dermomyotome of somites, from a common progenitor with skeletal muscle. However, many aspects of BAT embryonic development are not well understood.Hoxa5patterns other tissues at the cervical and brachial levels, including skeletal, neural and respiratory structures. Here, we show thatHoxa5also positively regulates BAT development, while negatively regulating formation of epaxial skeletal muscle. HOXA5 protein is expressed in embryonic preadipocytes and adipocytes as early as embryonic day 12.5.Hoxa5null mutant embryos and rare, surviving adults show subtly reduced iBAT and sBAT formation, as well as aberrant marker expression, lower adipocyte density and altered lipid droplet morphology. Conversely, the epaxial muscles that arise from a common dermomyotome progenitor are expanded inHoxa5mutants. Conditional deletion ofHoxa5withMyf5/Crecan reproduce both BAT and epaxial muscle phenotypes, indicating that HOXA5 is necessary withinMyf5-positive cells for proper BAT and epaxial muscle development. However, recombinase-based lineage tracing shows thatHoxa5does not act cell-autonomously to repress skeletal muscle fate. Interestingly,Hoxa5-dependent regulation of adipose-associated transcripts is conserved in lung and diaphragm, suggesting a shared molecular role forHoxa5in multiple tissues. Together, these findings establish a role forHoxa5in embryonic BAT development.

Controlled cellular energy conversion in brown adipose tissue thermogenesis

1978 ◽  
Vol 235 (3) ◽  
pp. R121-R129
Author(s):  
J. M. Horowitz ◽  
R. E. Plant
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Thermodynamic Description ◽  
Atp Synthesis ◽  
Brown Fat ◽  
Parallel Mechanisms ◽  
Fat Cell ◽  
Membrane Pump ◽  
Cellular Models ◽  
Brown Adipose

Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

scholarly journals CCAAT/enhancer-binding proteins α and β in brown adipose tissue: evidence for a tissue-specific pattern of expression during development

1994 ◽  
Vol 302 (3) ◽  
pp. 695-700 ◽  
Author(s):  
C Manchado ◽  
P Yubero ◽  
O Viñas ◽  
R Iglesias ◽  
F Villarroya ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Fetal Life ◽  
Inhibitory Protein ◽  
Adult Rats ◽  
Stage Of Development ◽  
Brown Adipose

CCAAT/enhancer-binding protein (C/EBP) alpha mRNA and its protein products C/EBP alpha and 30 kDa C/EBP alpha are expressed in rat brown-adipose tissue. Results also demonstrate the expression of C/EBP beta mRNA and its protein products C/EBP beta and liver inhibitory protein (LIP) in the tissue. The abundance of C/EBP alpha and C/EBP beta proteins in adult brown fat is similar to that found in adult liver. However, the expression of C/EBP alpha and C/EBP beta is specifically regulated in brown fat during development. C/EBP alpha, 30 kDa C/EBP alpha, C/EBP beta and LIP content is several-fold higher in fetal brown fat than in the adult tissue, or liver at any stage of development. Peak values are attained in late fetal life, in concurrence with the onset of transcription of the uncoupling protein (UCP) gene, the molecular marker of terminal brown-adipocyte differentiation. When adult rats are exposed to a cold environment, which is a physiological stimulus of brown-adipose tissue hyperplasia and UCP gene expression, a specific rise in C/EBP beta expression with respect to C/EBP alpha, 30 kDa C/EBP alpha and LIP is observed. Present data suggest that the C/EBP family of transcription factors has an important role in the development and terminal differentiation of brown-adipose tissue.

Cold-induced developmental changes in fat cell size and number in brown adipose tissue of the rat

1981 ◽  
Vol 240 (4) ◽  
pp. E379-E383 ◽  
Author(s):  
C. Senault ◽  
G. Cherqui ◽  
M. Cadot ◽  
R. Portet
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Acclimation ◽  
Cell Size ◽  
Brown Fat ◽  
Control Group ◽  
Fat Cells ◽  
Fat Cell ◽  
Brown Adipose ◽  
The Mean

Seven-week-old Long-Evans rats were acclimated to a constant temperature of either 28 degrees C (control group) or 5 degrees C (cold-acclimated group). Cold acclimation induced a 70% increase in the interscapular brown adipose tissue (IBAT) relative mass, a 35% increase in DNA content, and a 44% decrease in triglyceride (TG) content, which resulted in a 51% decrease of the TG/DNA ratio. A procedure is described by which brown fat cells were isolated, with a yield of 21% from the IBAT of the control group and of 38% in the cold-acclimated group. In both groups, the brown fat cells accounted for 35-37% of the total cells in the tissue. Cold acclimation induced decreases in the mean fat cell diameter (about 20%), the mean fat cell TG content (50%), and the fat cell TG/DNA ratio (50%). The total number of IBAT fat cells was significantly increased in cold-acclimated rats. It is concluded that cold acclimation involves a hyperplasia of the IBAT, associated with a decrease of fat cell size without any alteration of the fat cell-to-nonfat cell ratio.

An endocrine role for brown adipose tissue?

2013 ◽  
Vol 305 (5) ◽  
pp. E567-E572 ◽  
Author(s):  
Joan Villarroya ◽  
Rubén Cereijo ◽  
Francesc Villarroya
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Metabolic Diseases ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Fibroblast Growth Factor 21 ◽  
Current View ◽  
Brown Adipose ◽  
Endocrine Factors

White adipose tissue is recognized as both a site of energy storage and an endocrine organ that produces a myriad of endocrine factors called adipokines. Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis in mammals. The amount and activity of brown adipocytes are associated with protection against obesity and associated metabolic alterations. These effects of BAT are traditionally attributed to its capacity for the oxidation of fatty acids and glucose to sustain thermogenesis. However, recent data suggest that the beneficial effects of BAT could involve a previously unrecognized endocrine role through the release of endocrine factors. Several signaling molecules with endocrine properties have been found to be released by brown fat, especially under conditions of thermogenic activation. Moreover, experimental BAT transplantation has been shown to improve glucose tolerance and insulin sensitivity mainly by influencing hepatic and cardiac function. It has been proposed that these effects are due to the release of endocrine factors by brown fat, such as insulin-like growth factor I, interleukin-6, or fibroblast growth factor-21. Further research is needed to determine whether brown fat plays an endocrine role and, if so, to comprehensively identify which endocrine factors are released by BAT. Such research may reveal novel clues for the observed association between brown adipocyte activity and a healthy metabolic profile, and it could also enlarge a current view of potential therapeutic tools for obesity and associated metabolic diseases.

Stereospecific stimulation of brown adipocyte respiration by catecholamines via beta 1-adrenoreceptors

1980 ◽  
Vol 238 (6) ◽  
pp. E552-E563 ◽  
Author(s):  
L. Bukowiecki ◽  
N. Follea ◽  
A. Paradis ◽  
A. Collet
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Brown Adipocyte ◽  
Regulation Of Respiration ◽  
Beta Adrenergic ◽  
Interscapular Brown Adipose Tissue ◽  
Beta Agonists ◽  
Brown Adipose ◽  
Adrenergic Antagonists ◽  
20 Nm

Regulation of respiration by catecholamines was studied in adipocytes isolated from interscapular brown adipose tissue of warm-acclimated rats by rapid digestion of collagenase. (-)-Norepinephrine stimulated adipocyte respiration 10–12 times above basal values in less than 3 min. (Vmax = 410 +/- 29.5 nmol O2 . min-1 . 10(-6) cells-1). Stimulated respiration remained stable for at least 20 min, provided that cells were incubated in balanced salt media containing bicarbonate. The maximal capacity of total brown adipose tissue for norepinephrine-stimulated respitarion was estimated at 1.5 ml O2/min per rat. beta-Adrenergic agonists increased calorigenesis stereospecifically with an order of potency expected for respiratory stimulation via adrenoceptors of the beta 1-subtype: (-)-isoproterenol (1/2 Vmax = 2 nM) greater than (-)-norepinephrine (1/2 Vmax = 20 nM) approximately equal to (-)-epinephrine (1/2 Vmax = 40 nM) greater than corresponding (+)-stereoisomers. The alpha-adrenergic agonist phenylephrine (1/2 Vmax = 5 microM) stimulated adipocyte respiration as rapidly and as effectively as beta-agonists. Although alpha-adrenoreceptors are present in brown adipose tissue, studies with alpha- and beta-adrenergic antagonists revealed that norepinephrine elicits thermogenesis at physiological concentrations (less than or equal to 1 microM) predominantely via beta 1-adrenergic pathways.

Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology

1996 ◽  
Vol 270 (5) ◽  
pp. E776-E786 ◽  
Author(s):  
J. Kopecky ◽  
M. Rossmeisl ◽  
Z. Hodny ◽  
I. Syrovy ◽  
M. Horakova ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transgenic Mice ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Brown Fat ◽  
Small Cells ◽  
Cytochrome Oxidase Activity ◽  
Tissue Morphology ◽  
Brown Adipose ◽  
White Fat

C57BL6/J mice with the expression of the mitochondrial uncoupling protein (UCP) gene from the fat-specific aP2 gene promoter were used to study the mechanism by which the aP2-Ucp transgene affects adiposity and reduces high-fat diet induced obesity. In the transgenic mice, UCP synthesized in white fat was inserted into mitochondria, and oxygen uptake by epididymal fat fragments indicated UCP-induced thermogenesis. The respirometry data, UCP content, cytochrome oxidase activity, and tissue morphology suggested functional involution of brown fat. Despite 25- to 50-fold lower mitochondrial cytochrome oxidase activity in white than in brown fat cells, total oxidative capacity in white and brown adipose tissue is comparable. Appearance of novel small cells in the gonadal fat of the transgenic mice was associated with a higher DNA content than that of the nontransgenic mice. The results prove a potential of transgenically altered mitochondria in white fat to modulate adiposity and energy expenditure and suggest the existence of a yet unidentified site-specific link between energy metabolism in adipocytes and cellularity.

scholarly journals CYTOLOGICAL RESPONSES OF BROWN FAT TISSUE IN COLD-EXPOSED RATS

1964 ◽  
Vol 23 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Ivan L. Cameron ◽  
Robert E. Smith
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
Tritiated Thymidine ◽  
Control Level ◽  
Vascular Supply ◽  
Brown Fat ◽  
Fat Cell ◽  
Index Method ◽  
Synthetic Index ◽  
Brown Adipose

In young adult laboratory rats exposed to cold (6°C) the brown adipose tissue undergoes time-dependent increases in cellularity, vascular supply, and total mass. These changes are largely complete after 16 days in the cold and concurrent generally with the development of a thermoregulatory state not greatly dependent upon shivering. Histologically the brown fat changes from a tissue having both unilocular and multilocular fat cell types to one having almost exclusively the latter. During the first 6 to 12 hours in cold, the multilocular cells lose their lipid vacuoles and decrease in size, but these features are restored to normal by 24 hours. Cell proliferation, as estimated by the DNA synthetic index method (using tritiated thymidine autoradiography), appears in the reticuloendothelial cells of the brown fat at 1 day of cold exposure, becomes maximal at 4 days, and returns to the control level by 16 days. In animals injected with tritiated thymidine on the 3rd day of cold exposure and then maintained for 1 or more additional days in the cold, autoradiographs indicate that new brown fat (multilocular) cells arise by cytogenesis from reticuloendothelial progenitor cells and not by proliferation of existing brown fat cells. Throughout this and subsequent periods, cells of the epididymal white adipose tissue slowly decrease in size. Because a thermogenic role in cold acclimation has been established for the brown fat, the reported changes are regarded as adaptive responses to a cold environment.

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