Ontogenic Loss of Brown Adipose Tissue Sensitivity to β-Adrenergic Stimulation in the Ovine

Lomax, M.A.; Sadiq, Fouzia; Karamanlidis, Georgios; Karamitri, Angeliki; Trayhurn, Paul; Hazlerigg, David G.

doi:10.1210/en.2006-0918

Cited by 50 publications

(53 citation statements)

References 39 publications

(53 reference statements)

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“…2H, where BAT from FPLD animals displays a white-like appearance. This phenomenon has been observed in genetically manipulated animal models (30,31) and in humans with a reduced potential of adipose precursor cells (32).…”

Section: Fpld Mice Are Unable To Accumulate Fatmentioning

confidence: 78%

The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation

Wojtanik

Edgemon

Viswanadha

et al. 2009

Journal of Lipid Research

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We investigated the role of LMNA in adipose tissue by developing a novel mouse model of lipodystrophy. Transgenic mice were generated that express the LMNA mutation that causes familial partial lipodystrophy of the Dunnigan type (FPLD2). The phenotype observed in FPLD-transgenic mice resembles many of the features of human FPLD2, including lack of fat accumulation, insulin resistance, and enlarged, fatty liver. Similar to the human disease, FPLD-transgenic mice appear to develop normally, but after several weeks they are unable to accumulate fat to the same extent as their wild-type littermates. One poorly understood aspect of lipodystrophies is the mechanism of fat loss. To this end, we have examined the effects of the FPLD2 mutation on fat cell function. Contrary to the current literature, which suggests FPLD2 results in a loss of fat, we found that the key mechanism contributing to the lack of fat accumulation involves not a loss, but an apparent inability of the adipose tissue to renew itself. Specifically, preadipocytes are unable to differentiate into mature and fully functional adipocytes. These findings provide insights not only for the treatment of lipodystrophies, but also for the study of adipogenesis, obesity, and insulin resistance.-Wojtanik, K. M., K. Edgemon, S. Viswanadha, B. Lindsey, M. Haluzik, W. Chen, G. Poy, M. Reitman, and C. Londos. The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation.

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Section: Fpld Mice Are Unable To Accumulate Fatmentioning

confidence: 78%

The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation

Wojtanik

Edgemon

Viswanadha

et al. 2009

Journal of Lipid Research

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“…We have previously demonstrated that replacement of BAT with WAT in newborn lambs is due to down-regulation of adrenergic induced Ucp1 activation and repression of Pgc-1␣ expression (7). The question as to whether mature adipocytes can "interconvert" or whether separate pools of white and brown progenitor cells mediate "transdifferentiation" of these tissues has not been resolved.…”

Section: Discussionmentioning

confidence: 99%

“…Transdifferentiation from white to brown adipose tissue and/or vice versa has been reported in many species, including rodents, cats, dogs, ruminants (2)(3)(4)(5)(6)(7)(8)(9), and humans (10). Studies have suggested the existence of brown adipocytes in humans not only at birth but also within white fat depots in adult humans (11).…”

mentioning

confidence: 99%

Combinatorial Transcription Factor Regulation of the Cyclic AMP-response Element on the Pgc-1α Promoter in White 3T3-L1 and Brown HIB-1B Preadipocytes

Karamitri

Shore

Docherty

et al. 2009

Journal of Biological Chemistry

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Cold stress in rodents increases the expression of UCP1 and PGC-1␣ in brown and white adipose tissue. We have previously reported that C/EBP␤ specifically binds to the CRE on the proximal Pgc-1␣ promoter and increases forskolin-sensitive Pgc-1␣ and Ucp1 expression in white 3T3-L1 preadipocytes. Here we show that in mice exposed to a cold environment for 24 h, Pgc-1␣, Ucp1, and C/ebp␤ but not C/ebp␣ or C/ebp␦ expression were increased in BAT. Conversely, expression of the C/EBP dominant negative Chop10 was increased in WAT but not BAT during cold exposure. Reacclimatization of cold-exposed mice to a warm environment for 24 h completely reversed these changes in gene expression. In HIB-1B, brown preadipocytes, forskolin increased expression of Pgc-1␣, Ucp1, and C/ebp␤ early in differentiation and inhibited Chop10 expression. Employing chromatin immunoprecipitation, we demonstrate that C/EBP␤, CREB, ATF-2, and CHOP10 are bound to the Pgc-1␣ proximal CRE, but CHOP10 does not bind in HIB-1B cell lysates. Forskolin stimulation and C/EBP␤ overexpression in 3T3-L1 cells increased C/EBP␤ and CREB but displaced ATF-2 and CHOP10 binding to the Pgc-1␣ proximal CRE. Overexpression of ATF-2 and CHOP10 in 3T3-L1 cells decreased Pgc-1␣ transcription. Knockdown of Chop10 in 3T3-L1 cells using siRNA increased Pgc-1␣ transcription, whereas siRNA against C/ebp␤ in HIB-1B cells decreased Pgc-1␣ and Ucp1 expression. We conclude that the increased cAMP stimulation of Pgc-1␣ expression is regulated by the combinatorial effect of transcription factors acting at the CRE on the proximal Pgc-1␣ promoter.

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“…In cattle and sheep at birth, the different AT depots, except for the subcutaneous depot in some bovine breeds , can be considered as brown due to the high expression of UCP1, cytochrome c oxidase and ADP/ATP carrier protein (Casteilla et al, 1987;Casteilla et al, 1989). UCP1 mRNA reaches its highest level in the various BAT at birth and is no longer detectable 2 days later in cattle (Casteilla et al, 1987), and sheep, probably as the result of a sharp decline in the expression of peroxisome proliferatoractivated receptor-a (PPARa) and peroxisome proliferatoractivated receptor-c coactivator-1a (PGC-1a) (Lomax et al, 2007). In cattle, since the estimated number of cells remains constant during the first week following birth, it has been thought that a transdifferentiation of brown into white adipocytes occurs.…”

Section: Dynamics Of At Growthmentioning

confidence: 99%

Ontogenesis of muscle and adipose tissues and their interactions in ruminants and other species

Bonnet

Cassar-Malek

Chilliard

et al. 2010

Animal

110

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The lean-to-fat ratio, that is, the relative masses of muscle and adipose tissue, is a criterion for the yield and quality of bovine carcasses and meat. This review describes the interactions between muscle and adipose tissue (AT) that may regulate the dynamic balance between the number and size of muscle v. adipose cells. Muscle and adipose tissue in cattle grow by an increase in the number of cells (hyperplasia), mainly during foetal life. The total number of muscle fibres is set by the end of the second trimester of gestation. By contrast, the number of adipocytes is never set. Number of adipocytes increases mainly before birth until 1 year of age, depending on the anatomical location of the adipose tissue. Hyperplasia concerns brown pre-adipocytes during foetal life and white pre-adipocytes from a few weeks after birth. A decrease in the number of secondary myofibres and an increase in adiposity in lambs born from mothers severely underfed during early pregnancy suggest a balance in the commitment of a common progenitor into the myogenic or adipogenic lineages, or a reciprocal regulation of the commitment of two distinct progenitors. The developmental origin of white adipocytes is a subject of debate. Molecular and histological data suggested a possible transdifferentiation of brown into white adipocytes, but this hypothesis has now been challenged by the characterization of distinct precursor cells for brown and white adipocytes in mice. Increased nutrient storage in fully differentiated muscle fibres and adipocytes, resulting in cell enlargement (hypertrophy), is thought to be the main mechanism, whereby muscle and fat masses increase in growing cattle. Competition or prioritization between adipose and muscle cells for the uptake and metabolism of nutrients is suggested, besides the successive waves of growth of muscle v. adipose tissue, by the inhibited or delayed adipose tissue growth in bovine genotypes exhibiting strong muscular development. This competition or prioritization occurs through cellular signalling pathways and the secretion of proteins by adipose tissue (adipokines) and muscle (myokines), putatively regulating their hypertrophy in a reciprocal manner. Further work on the mechanisms underlying cross-talk between brown or white adipocytes and muscle fibres will help to achieve better understanding as a prerequisite to improving the control of body growth and composition in cattle.

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Ontogenic Loss of Brown Adipose Tissue Sensitivity to β-Adrenergic Stimulation in the Ovine

Cited by 50 publications

References 39 publications

The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation

The role of LMNA in adipose: a novel mouse model of lipodystrophy based on the Dunnigan-type familial partial lipodystrophy mutation

Combinatorial Transcription Factor Regulation of the Cyclic AMP-response Element on the Pgc-1α Promoter in White 3T3-L1 and Brown HIB-1B Preadipocytes

Ontogenesis of muscle and adipose tissues and their interactions in ruminants and other species

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