Contrasting adrenergic effects on lipoprotein lipase gene expression in the brown adipose tissue of intact mice and in cultured brown adipocytes from mice

The regulation of lipoprotein lipase gene expression in brown adipose tissue was studied. Rats were preacclimated to 21 degrees C. Exposure to cold (4 degrees C) resulted in a rapid increase in the level of lipoprotein lipase mRNA in the tissue. The level peaked (expressed per microgram total RNA) after approximately 8 h and then slowly declined. The increased lipoprotein lipase mRNA level was not due to an increased stability of the mRNA, but, in a transition event from a high to a low expression of the lipoprotein lipase gene, a transcription-dependent process was recruited that accelerated the breakdown of lipoprotein lipase mRNA. Norepinephrine injections increased lipoprotein lipase mRNA levels in the tissue; this effect was mediated via a beta-adrenergic receptor. The effect of cold could be mimicked by norepinephrine injections, and these two effects were not additive, indicating that the cold effect was mediated by norepinephrine. The lipoprotein lipase mRNA level was also increased by insulin injections (into fasted animals); thus an increase in lipoprotein lipase gene expression in brown adipose tissue may be induced via two different stimuli, which, intracellularly, would be mediated via different signaling systems. In all investigated conditions, the changes in lipoprotein lipase mRNA levels observed here were parallelled by alterations in lipoprotein lipase activity reported earlier from this laboratory. It was therefore concluded that, under the conditions studied, lipoprotein lipase activity in brown adipose tissue was primarily regulated at the transcriptional level.

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Adrenergic stimulation of lipoprotein lipase gene expression in rat brown adipocytes differentiated in culture: mediation via β3- and α1-adrenergic receptors

Biochemical Journal ◽

10.1042/bj3210759 ◽

1997 ◽

Vol 321 (3) ◽

pp. 759-767 ◽

Cited By ~ 21

Author(s):

Pertti KUUSELA ◽

Stefan REHNMARK ◽

Anders JACOBSSON ◽

Barbara CANNON ◽

Jan NEDERGAARD

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Lipoprotein Lipase ◽

Direct Effect ◽

Mrna Levels ◽

Adrenergic Stimulation ◽

Brown Adipocytes ◽

Brown Adipose ◽

Lpl Gene

In order to investigate whether the positive effect of adrenergic stimulation on lipoprotein lipase (LPL) gene expression in brown adipose tissue is a direct effect on the brown adipocytes themselves, the expression of the LPL gene was investigated by measuring LPL mRNA levels in brown adipocytes, isolated as precursors from the brown adipose tissue of rats and grown in culture in a fully defined medium before experimentation. Addition of noradrenaline led to an enhancement of LPL gene expression; the mRNA levels increased as a linear function of time for at least 5 h and were finally approx. 3 times higher than in control cells, an increase commensurate with that seen in vivoin both LPL mRNA levels and LPL activity during physiological stimulation. The increase was dependent on transcription. The effect of noradrenaline showed simple MichaelisŐMenten kinetics with an EC50 of approx. 11 nM. β3-Agonists (BRL-37344 and CGP-12177) could mimic the effect of noradrenaline; the β1-agonist dobutamine and the β2-agonist salbutamol could not; the α1-agonist cirazoline had only a weak effect. The effect of noradrenaline was fully inhibited by the β-antagonist propranolol and was halved by the α1-antagonist prazosin; the α2-antagonist yohimbine was without effect. An increase in LPL mRNA level similar to (but not significantly exceeding) that caused by noradrenaline could also be induced by the cAMP-elevating agents forskolin and cholera toxin, and 8-Br-cAMP also increased LPL mRNA levels. The increase in LPL gene expression was not mediated via an increase in the level of an intermediary proteinaceous factor. It is concluded that the physiologically induced increase in LPL gene expression is a direct effect of noradrenaline on the brown adipocytes themselves, mediated via a dominant β3-adrenergic pathway and an auxillary α1-adrenergic pathway which converge at a regulatory point in transcriptional control.

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Endothelin-1, but not endothelin-3, suppresses lipoprotein lipase gene expression in brown adipocytes differentiated in culture

European Journal of Pharmacology Molecular Pharmacology ◽

10.1016/0922-4106(95)90186-8 ◽

1995 ◽

Vol 291 (1) ◽

pp. 33-41 ◽

Cited By ~ 8

Author(s):

Yoko Uchida ◽

Kaoru Irie ◽

Fujiko Tsukahara ◽

Ken-ichi Ohba ◽

Akira Ogawa ◽

...

Keyword(s):

Gene Expression ◽

Lipoprotein Lipase ◽

Lipase Gene ◽

Brown Adipocytes ◽

Endothelin 1 ◽

Lipoprotein Lipase Gene ◽

Endothelin 3

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Peroxisome Proliferator-Activated Receptors-α and -γ, and cAMP-Mediated Pathways, Control Retinol-Binding Protein-4 Gene Expression in Brown Adipose Tissue

Endocrinology ◽

10.1210/en.2011-1367 ◽

2012 ◽

Vol 153 (3) ◽

pp. 1162-1173 ◽

Cited By ~ 33

Author(s):

Meritxell Rosell ◽

Elayne Hondares ◽

Sadahiko Iwamoto ◽

Frank J. Gonzalez ◽

Martin Wabitsch ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Retinol Binding Protein ◽

Peroxisome Proliferator ◽

Brown Adipocytes ◽

Retinol Binding Protein 4 ◽

White Adipocytes ◽

Brown Adipose ◽

Rbp4 Gene

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.

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Postnatal selective suppression of lipoprotein lipase gene expression in brown adipose tissue (relative to the expression of the gene for the uncoupling protein) is not due to adrenergic insensitivity: a possible specific inhibitory effect of colostrum

Biochemical Journal ◽

10.1042/bj3140261 ◽

1996 ◽

Vol 314 (1) ◽

pp. 261-267 ◽

Cited By ~ 9

Author(s):

María-Jesus OBREGÓN ◽

Barbara CANNON ◽

Jan NEDERGAARD

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Lipoprotein Lipase ◽

Uncoupling Protein ◽

Mrna Levels ◽

Selective Suppression ◽

Brown Adipose ◽

Adrenergic Antagonist ◽

Lpl Gene

The levels of mRNA coding for the uncoupling protein (UCP) and for lipoprotein lipase (LPL) were monitored in the brown adipose tissue of newborn rat pups. At 5 h after birth, the mRNA levels of UCP and LPL were high in pups exposed singly to 28 °C and low in pups kept singly at thermoneutrality (36 °C); in pups staying with the dam, the UCP mRNA levels were intermediate. However, the LPL mRNA levels were lower in pups staying with the dam than in pups at 36 °C, implying that factors additional to environmental temperature influenced LPL gene expression. Injection of noradrenaline into pups at thermoneutrality (36 °C) led to increases in UCP and LPL gene expression, but noradrenaline injections had no further effect in cold-exposed pups. The adrenergic effects were mediated via β-adrenergic receptors. The cold-induced increases in both UCP and LPL gene expression were abolished by the β-adrenergic antagonist propranolol. Thus differences in adrenergic responsiveness could not explain the differential expression of the UCP and LPL genes observed in pups staying with the dam. The presence of a physiological suppressor was examined by feeding single pups at 28 °C with different foods: nothing, water, Intralipid, cow's milk, rat milk and rat colostrum. None of these agents led to suppression of UCP gene expression, but colostrum led to a selective suppression of LPL gene expression. It was concluded that the genes for UCP and LPL were responsive to adrenergic stimuli immediately after birth, and it is suggested that a component of rat colostrum can selectively suppress LPL gene expression.

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Oleoyl-oestrone inhibits lipogenic, but maintains thermogenic, gene expression of brown adipose tissue in overweight rats

Bioscience Reports ◽

10.1042/bsr20080089 ◽

2009 ◽

Vol 29 (4) ◽

pp. 237-243 ◽

Cited By ~ 5

Author(s):

María del Mar Romero ◽

José A. Fernández-López ◽

Montserrat Esteve ◽

Marià Alemany

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Uncoupling Protein ◽

Critical Factor ◽

Hormone Sensitive Lipase ◽

Male Rats ◽

Acid Oxidation ◽

Lipase Gene ◽

Brown Adipose

In the present study we intended to determine how BAT (brown adipose tissue) maintained thermogenesis under treatment with OE (oleoyl-oestrone), a powerful slimming hormone that sheds off body lipid but maintains the metabolic rate. Overweight male rats were subjected to daily gavages of 10 nmol/g of OE or vehicle (control) for 10 days. A PF (pair-fed) vehicle-receiving group was used to discount the effects attributable to energy availability limitation. Interscapular BAT mass, lipid, DNA, mRNA and the RT-PCR (real-time PCR) expression of lipid and energy metabolism genes for enzymes and regulatory proteins were measured. BAT mass and lipid were decreased in OE and PF, with the latter showing a marked reduction in tissue mRNA. Maintenance of perilipin gene expression in PF and OE rats despite the loss of lipid suggests the preservation of the vacuolar interactive surface, a critical factor for thermogenic responsiveness. OE and, to a lesser extent, PF maintained the expression of genes controlling lipolysis and fatty acid oxidation, but markedly decreased the expression of those genes involved in lipogenic and acyl-glycerol synthesis. OE did not affect UCP1 (uncoupling protein 1) (decreased in PF), β3 adrenergic receptors or hormone-sensitive lipase gene mRNAs, which may translate in maintaining a full thermogenic system potential. OE rats were able to maintain a less energetically stressed BAT (probably through glucose utilization) than PF rats. These changes were not paralleled in PF rats, in which lower thermogenesis and glucose preservation resulted in a heavier toll on internal fat stores. Thus the mechanism of action of OE is more complex and tissue-specific than previously assumed.

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