Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes

Abstract

Multilocular, mitochondria-rich adipocytes appear in white adipose tissue (WAT) of rats treated with the beta3-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 ( approximately 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.

Structure–effect relation of C18 long-chain fatty acids in the reduction of body weight in rats

“…Acquirement of BAT-like features by WAT can be provoked by physiological conditions, such as cold stress, 22 or by pharmacological intervention, such as b 3 -adrenergic stimulation. 23 Moreover, UCP1 expression in WAT is related to body weight loss in obese and UCP1 transgenic mice 24,25 and can also occur in human white adipocytes. 26 Stimulation of b 3 -adrenergic receptors increases intracellular cAMP, thereby activating protein kinase A (PKA), which then phosphorylates the UCP1 transcription factor CREB and hormone-sensitive lipase, resulting in UCP1 Effect of C18 fatty acids on body weight O Vögler et al expression and lipolysis of stored fat from adipocyte lipid droplets.…”

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

“…The ability of brown adipocytes to dissipate energy as heat results from the activity of uncoupling protein 1 (UCP1), which is located in the inner mitochondrial membrane and uncouples the electron transport chain from ATP production (extensively reviewed in Cannon and Nedergaard1). In addition to classical brown adipose tissue (BAT) depots, pockets of UCP1‐positive, multilocular adipocytes have also been described within white adipose tissue (WAT) from rodents following cold exposure,2, 3, 4 treatment with a beta 3‐adrenergic agonist,5 or exercise training 6. These adipocytes are commonly referred to as beige, brite (from brown in white), inducible, or recruitable, reviewed in Chechi et al 7 and seem to result from the transdifferentiation of previously unilocular, white adipocytes4, 5 and from the de novo differentiation of precursor cells 8.…”

Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

“…Indeed, when studied under the conditions of the above treatments, AMPK in WAT and other tissues was found to be activated (Jelenik et al 2010;Kopecky et al 2009;Orci et al 2004;Ye et al 2006). Concerning the mechanism of energy expenditure induced by the treatments, mitochondrial uncoupling mediated by UCP1 in WAT adipocytes (Orci et al 2004;Tiraby et al 2003;Petrovic et al 2010;Collins et al 1997;Guerra et al 1998;Himms-Hagen et al 2000) could be involved in most of the cases. Further studies are required to learn more about the mechanisms underlying the induction of energy dissipating adipocytes in response to treatments inducing UCP1 in adipose tissue.…”

“…Further studies are required to learn more about the mechanisms underlying the induction of energy dissipating adipocytes in response to treatments inducing UCP1 in adipose tissue. It needs to be determined whether the induction of BAT precursor cells, trans-differentiation of mature white adipocytes into their brown counterparts (Himms-Hagen et al 2000;Cinti 2002), or the formation of brown-adipocyte-like cells, a new adipocyte subtype inducible by TZD [i.e., 'brite'cells (Petrovic et al 2010)], is responsible for the induction of UCP1-containing adipocytes in white fat.…”