scholarly journals Calcium-SANDOZ®-induced erythrocyte exovesiculation and internalization of hemichromic material into rat brown adipocytes

2011 ◽  
Vol 63 (2) ◽  
pp. 309-317
Author(s):  
Milica Markelic ◽  
Ksenija Velickovic ◽  
I. Golic ◽  
Mirela Ukropina ◽  
Maja Cakic-Milosevic ◽  
...  

An ultramicroscopic study of brown adipose tissue (BAT) of rats treated with Ca-SANDOZ? (480 mg/l) for 3 days, revealed erythrocyte exovesiculation and migratory erythrocytic complexes from the capillaries to adipocyte cytoplasm and mitochondria. Two types of erythrocytic material transfer were observed: (i) numerous exocytic vesicles with electron dense material leaving the erythrocytes; (ii) furcated complexes with microholes, embedded in amorphous material. The content of red blood cell (RBC) complexes passed through the capillaries and transferred to the brown adipocytes where it was detectable in the cytoplasm and mitochondria. Light microscopy confirmed sphenoechinocytic transformation of the RBCs in the blood smears of the Ca-SANDOZ? treated rats.

2020 ◽  
Vol 117 (26) ◽  
pp. 15055-15065 ◽  
Author(s):  
Mengxi Jiang ◽  
Tony E. Chavarria ◽  
Bingbing Yuan ◽  
Harvey F. Lodish ◽  
Nai-Jia Huang

Phosphocholine phosphatase-1 (PHOSPHO1) is a phosphocholine phosphatase that catalyzes the hydrolysis of phosphocholine (PC) to choline. Here we demonstrate that the PHOSPHO1 transcript is highly enriched in mature brown adipose tissue (BAT) and is further induced by cold and isoproterenol treatments of BAT and primary brown adipocytes. In defining the functional relevance of PHOPSPHO1 in BAT thermogenesis and energy metabolism, we show that PHOSPHO1 knockout mice are cold-tolerant, with higher expression of thermogenic genes in BAT, and are protected from high-fat diet-induced obesity and development of insulin resistance. Treatment of mice with the PHOSPHO1 substrate phosphocholine is sufficient to induce cold tolerance, thermogenic gene expression, and allied metabolic benefits. Our results reveal a role of PHOSPHO1 as a negative regulator of BAT thermogenesis, and inhibition of PHOSPHO1 or enhancement of phosphocholine represent innovative approaches to manage the metabolic syndrome.


Author(s):  
Fubiao Shi ◽  
Sheila Collins

Abstractβ-adrenergic receptors (βARs) are well established for conveying the signal from catecholamines to adipocytes. Acting through the second messenger cyclic adenosine monophosphate (cAMP) they stimulate lipolysis and also increase the activity of brown adipocytes and the ‘browning’ of adipocytes within white fat depots (so-called ‘brite’ or ‘beige’ adipocytes). Brown adipose tissue mitochondria are enriched with uncoupling protein 1 (UCP1), which is a regulated proton channel that allows the dissipation of chemical energy in the form of heat. The discovery of functional brown adipocytes in humans and inducible brown-like (‘beige’ or ‘brite’) adipocytes in rodents have suggested that recruitment and activation of these thermogenic adipocytes could be a promising strategy to increase energy expenditure for obesity therapy. More recently, the cardiac natriuretic peptides and their second messenger cyclic guanosine monophosphate (cGMP) have gained attention as a parallel signaling pathway in adipocytes, with some unique features. In this review, we begin with some important historical work that touches upon the regulation of brown adipocyte development and physiology. We then provide a synopsis of some recent advances in the signaling cascades from β-adrenergic agonists and natriuretic peptides to drive thermogenic gene expression in the adipocytes and how these two pathways converge at a number of unexpected points. Finally, moving from the physiologic hormonal signaling, we discuss yet another level of control downstream of these signals: the growing appreciation of the emerging roles of non-coding RNAs as important regulators of brown adipocyte formation and function. In this review, we discuss new developments in our understanding of the signaling mechanisms and factors including new secreted proteins and novel non-coding RNAs that control the function as well as the plasticity of the brown/beige adipose tissue as it responds to the energy needs and environmental conditions of the organism.


Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1162-1173 ◽  
Author(s):  
Meritxell Rosell ◽  
Elayne Hondares ◽  
Sadahiko Iwamoto ◽  
Frank J. Gonzalez ◽  
Martin Wabitsch ◽  
...  

Retinol binding protein-4 (RBP4) is a serum protein involved in the transport of vitamin A. It is known to be produced by the liver and white adipose tissue. RBP4 release by white fat has been proposed to induce insulin resistance. We analyzed the regulation and production of RBP4 in brown adipose tissue. RBP4 gene expression is induced in brown fat from mice exposed to cold or treated with peroxisome proliferator-activated receptor (PPAR) agonists. In brown adipocytes in culture, norepinephrine, cAMP, and activators of PPARγ and PPARα induced RBP4 gene expression and RBP4 protein release. The induction of RBP4 gene expression by norepinephrine required intact PPAR-dependent pathways, as evidenced by impaired response of the RBP4 gene expression to norepinephrine in PPARα-null brown adipocytes or in the presence of inhibitors of PPARγ and PPARα. PPARγ and norepinephrine can also induce the RBP4 gene in white adipocytes, and overexpression of PPARα confers regulation by this PPAR subtype to white adipocytes. The RBP4 gene promoter transcription is activated by cAMP, PPARα, and PPARγ. This is mediated by a PPAR-responsive element capable of binding PPARα and PPARγ and required also for activation by cAMP. The induction of the RBP4 gene expression by norepinephrine in brown adipocytes is protein synthesis dependent and requires PPARγ-coactivator-1-α, which acts as a norepinephine-induced coactivator of PPAR on the RBP4 gene. We conclude that PPARγ- and PPARα-mediated signaling controls RBP4 gene expression and releases in brown adipose tissue, and thermogenic activation induces RBP4 gene expression in brown fat through mechanisms involving PPARγ-coactivator-1-α coactivation of PPAR signaling.


2017 ◽  
Vol 39 ◽  
pp. 101-109 ◽  
Author(s):  
Mandana Pahlavani ◽  
Fitia Razafimanjato ◽  
Latha Ramalingam ◽  
Nishan S. Kalupahana ◽  
Hanna Moussa ◽  
...  

Endocrinology ◽  
2013 ◽  
Vol 154 (9) ◽  
pp. 2992-3000 ◽  
Author(s):  
Marta Giralt ◽  
Francesc Villarroya

Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis in mammals. Rodent studies indicated that BAT thermogenic activity may protect against obesity. Recent findings using novel radiodiagnosis procedures revealed unanticipated high activity of BAT in adult humans. Moreover, complex processes of cell differentiation leading to the appearance of active brown adipocytes have been recently identified. The brown adipocytes clustered in defined anatomical BAT depots of rodents arise from mesenchymal precursor cells common to the myogenic cell lineage. They are being called “classical” or “developmentally programmed” brown adipocytes. However, brown adipocytes may appear after thermogenic stimuli at anatomical sites corresponding to white adipose tissue (WAT). This process is called the “browning” of WAT. The brown adipocytes appearing in WAT derive from precursor cells different from those in classical BAT and are closer to the white adipocyte cell lineage. The brown adipocytes appearing in WAT are often called “inducible, beige, or brite.” The appearance of these inducible brown adipocytes in WAT may also involve transdifferentiation processes of white-to-brown adipose cells. There is no evidence that the ultimate thermogenic function of the beige/brite adipocytes differs from that of classical brown adipocytes, although some genetic data in rodents suggest a relevant role of the browning process in protection against obesity. Although the activation of classical BAT and the browning process share common mechanisms of induction (eg, noradrenergic-mediated induction by cold), multiple novel adrenergic-independent endocrine factors that activate BAT and the browning of WAT have been identified recently. In adult humans, BAT is mainly composed of beige/brite adipocytes, although recent data indicate the persistence of classical BAT at some anatomical sites. Understanding the biological processes controlling brown adipocyte activity and differentiation could help the design of BAT-focused strategies to increase energy expenditure and fight against obesity.


2000 ◽  
Vol 279 (3) ◽  
pp. C670-C681 ◽  
Author(s):  
J. Himms-Hagen ◽  
A. Melnyk ◽  
M. C. Zingaretti ◽  
E. Ceresi ◽  
G. Barbatelli ◽  
...  

Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the β3-adrenoceptor agonist, CL-316243 (CL). Objectives were to determine whether these multilocular adipocytes derived from cells that already existed in the WAT or from proliferation of precursor cells and whether new mitochondria contained in them were typical brown adipocyte mitochondria. Use of 5-bromodeoxyuridine to identify cells that had undergone mitosis during the CL treatment showed that most multilocular cells derived from cells already present in the WAT. Morphological techniques showed that at least a subpopulation of unilocular adipocytes underwent conversion to multilocular mitochondria-rich adipocytes. A small proportion of multilocular adipocytes (∼8%) was positive for UCP1 by immunohistochemistry. Biochemical techniques showed that mitochondrial protein recovered from WAT increased 10-fold and protein isolated from brown adipose tissue (BAT) doubled in CL-treated rats. Stained gels showed a different protein composition of new mitochondria isolated from WAT from that of mitochondria isolated from BAT. Western blotting showed new mitochondria in WAT to contain both UCP1, but at a much lower concentration than in BAT mitochondria, and UCP3, at a higher concentration than that in BAT mitochondria. We hypothesize that multilocular adipocytes present at 7 days of CL treatment have two origins. First, most come from convertible unilocular adipocytes that become multilocular and make many mitochondria that contain UCP3. Second, some come from a cell that gives rise to more typical brown adipocytes that express UCP1.


Author(s):  
A.P. Stepanchuk

The risk of developing metabolic complications in obesity depends on the topography of excess adipose tissue. Adipose tissue is the main source of energy and also performs an endocrine function secreting substances that affect the sensitivity of tissues to insulin. The article describes the characteristics of histological preparations of adipose tissue samples taken from the omentum of middle-aged human cadavers with no confirmed diseases of the digestive system and of subcutaneous adipose tissue samples from interscapular region in the human dead foetuses. Microscopy of sections of adipose tissue from the omentum and subcutaneous adipose tissue from the interscapular region of the foetus revealed that it consisted of lobes and microvessels. Lobes of adipose tissue of a human large omentum consist of polygonal white adipocytes containing in their cytoplasm a nucleus displaced to the periphery and a fat drop. The subcutaneous adipose tissue taken from the interscapular region of the foetus consists of brown adipocytes with a nucleus located in the centre of the cytoplasm and surrounded by numerous fat droplets. Brown adipocytes when compared with white adipocyted are smaller and rounded in shape. Brown adipose tissue predominates in women than in men. Brown adipose tissue is not active all the time, but only at low ambient temperatures. In women, brown adipocytes are more saturated with mitochondria than in men. Adipose tissue of a human omentum can be a source of graft implant for restoring abdominal organ defects during extensive surgical operations.


2018 ◽  
Author(s):  
Adilson Guilherme ◽  
David J Pedersen ◽  
Felipe Henriques ◽  
Alexander H. Bedard ◽  
Elizabeth Henchey ◽  
...  

ABSTRACTWhite adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of “beige” adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In contrast, selective ablation of FASN in brown adipocytes of mice (iUCP1FASNKO) failed to modulate sympathetic innervation and the thermogenic program in BAT. Surprisingly, DNL in brown adipocytes was also dispensable in maintaining euthermia when UCP1FASNKO mice were cold-exposed. These results indicate that DNL in white adipocytes influences long distance signaling to BAT, which can modify BAT sympathetic innervation and expression of genes involved in thermogenesis.


Sign in / Sign up

Export Citation Format

Share Document