scholarly journals Induction of functional uncoupling protein in guinea pigs infused with noradrenaline. Studies with isolated brown adipocytes

1987 ◽  
Vol 245 (2) ◽  
pp. 485-491 ◽  
Author(s):  
S A Cunningham ◽  
D G Nicholls
Keyword(s):  
Fatty Acid ◽  
Continuous Infusion ◽  
Guinea Pigs ◽  
Cold Adaptation ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Brown Adipocytes ◽  
Beta Agonists ◽  
Chronic Infusion ◽  
Isolated Adipocytes

Continuous infusion of noradrenaline over the interscapular brown fat of guinea pigs maintained at thermoneutrality (28-32 degrees C) induces changes similar to those after cold-adaptation. (1) Multilocular fat droplets appear within the brown adipocytes. (2) The number of mitochondria per adipocyte and the total number of adipocytes both increase. (3) Noradrenaline addition to isolated adipocytes causes near maximal uncontrolled respiration. (4) The cells become more sensitive to fatty acid-induced uncoupling. (5) The tissue-specific uncoupling protein per mg of mitochondrial protein is increased 5-fold. Specific alpha- and beta-agonists were also chronically infused. (6) Separate infusion of phenylephrine or isoprenaline was not able to stimulate mitochondriogenesis or hyperplasia. (7) Adipocytes from these animals could not be uncoupled by acute noradrenaline. (8) Simultaneous chronic infusion of phenylephrine and isoprenaline reproduced the effects of chronic noradrenaline infusion.

Cold adaptation in guinea pig at level of isolated brown adipocyte

1986 ◽  
Vol 250 (2) ◽  
pp. C228-C235 ◽  
Author(s):  
J. Rafael ◽  
W. Fesser ◽  
D. G. Nicholls
Keyword(s):  
Guinea Pig ◽  
Cold Acclimation ◽  
Guinea Pigs ◽  
Cold Adaptation ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Respiratory Control ◽  
Cell Number ◽  
Brown Adipocyte ◽  
Brown Adipose

Isolated brown adipocytes were prepared from guinea pigs acclimated to 28 degrees C or exposed to 4-8 degrees C for periods of up to 3 wk. Cells from warm-adapted animals retained respiratory control when stimulated with norepinephrine. Cells from guinea pigs exposed to cold for 4-21 days showed a much greater respiratory response to norepinephrine due to enhanced uncoupling rather than enhanced substrate supply. After 7 days of cold acclimation, norepinephrine-stimulated respiration became uncontrolled and was limited only by the maximal respiratory capacity of the mitochondria. Three weeks of cold acclimation were accompanied by a doubling of total cell number, a doubling of the mitochondrial protein per adipocyte, and a sixfold increase in the norepinephrine-stimulated respiration per in situ mitochondrion with no change in respiratory chain capacity. The induction of norepinephrine-stimulated respiration correlated with the appearance of high-affinity purine nucleotide binding sites on the mitochondria, diagnostic of the uncoupling protein. If the results are extrapolated to the whole animal, they indicate that brown adipose tissue makes little contribution to thermogenesis in the warm-adapted guinea pig but may account for most or all the increment seen on cold adaptation.

Increased response to noradrenaline of isolated brown adipocytes from guinea pigs during cold-adaptation

1986 ◽  
Vol 14 (2) ◽  
pp. 282-283 ◽  
Author(s):  
JOHANNES RAFAEL ◽  
WALTRAUD FESSER ◽  
DAVID G. NICHOLLS
Keyword(s):  
Guinea Pigs ◽  
Cold Adaptation ◽  
Brown Adipocytes

Development and activation of brown fat in rats with pheochromocytoma PC 12 tumors

1983 ◽  
Vol 245 (3) ◽  
pp. C172-C177 ◽  
Author(s):  
D. Ricquier ◽  
G. Mory ◽  
M. Nechad ◽  
M. Combes-George ◽  
J. Thibault
Keyword(s):  
Cold Adaptation ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Total Content ◽  
Sympathetic Nerves ◽  
Cellular Growth ◽  
Trophic Factors ◽  
Marked Rise ◽  
Brown Adipose ◽  
Specific Amount

To study the neurohormonal determinism of cellular growth and differentiation and mitochondrial development in brown adipose tissue (BAT), this organ was analyzed in rats bearing uncloned or cloned (PC 12) pheochromocytoma; comparison was made with cold adaptation. Both uncloned and PC 12 tumors induced an enlargement of tissue weight and DNA total content, although smaller than during cold adaptation. The following striking modifications were observed in rats bearing PC 12 tumors: strong vasodilation, increase in protein and phospholipid percentage, alteration of the fatty acid composition of phospholipids, increase in mitochondrial protein, large increase of the GDP binding to isolated mitochondria, and marked rise in specific amount of 32,000-dalton uncoupling protein (ascertained using immunological approach). It is concluded that secretions of PC 12 tumors can induce the same alterations in BAT as does the sympathetic system during cold adaptation of animals. An important contribution of norepinephrine to these effects is evidenced, but a specific function of other trophic factors secreted by PC 12 cells and by sympathetic nerves can be postulated.

scholarly journals Uncoupling Lipid Metabolism from Inflammation through Fatty Acid Binding Protein-Dependent Expression of UCP2

2015 ◽  
Vol 35 (6) ◽  
pp. 1055-1065 ◽  
Author(s):  
Hongliang Xu ◽  
Ann V. Hertzel ◽  
Kaylee A. Steen ◽  
Qigui Wang ◽  
Jill Suttles ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Er Stress ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
Ucp2 Expression ◽  
Elevated Expression

Chronic inflammation in obese adipose tissue is linked to endoplasmic reticulum (ER) stress and systemic insulin resistance. Targeted deletion of the murine fatty acid binding protein (FABP4/aP2) uncouples obesity from inflammation although the mechanism underlying this finding has remained enigmatic. Here, we show that inhibition or deletion of FABP4/aP2 in macrophages results in increased intracellular free fatty acids (FFAs) and elevated expression of uncoupling protein 2 (UCP2) without concomitant increases in UCP1 or UCP3. Silencing of UCP2 mRNA in FABP4/aP2-deficient macrophages negated the protective effect of FABP loss and increased ER stress in response to palmitate or lipopolysaccharide (LPS). Pharmacologic inhibition of FABP4/aP2 with the FABP inhibitor HTS01037 also upregulated UCP2 and reduced expression of BiP, CHOP, and XBP-1s. Expression of native FABP4/aP2 (but not the non-fatty acid binding mutant R126Q) into FABP4/aP2 null cells reduced UCP2 expression, suggesting that the FABP-FFA equilibrium controls UCP2 expression. FABP4/aP2-deficient macrophages are resistant to LPS-induced mitochondrial dysfunction and exhibit decreased mitochondrial protein carbonylation and UCP2-dependent reduction in intracellular reactive oxygen species. These data demonstrate that FABP4/aP2 directly regulates intracellular FFA levels and indirectly controls macrophage inflammation and ER stress by regulating the expression of UCP2.

scholarly journals NT3/TrkC Pathway Modulates the Expression of UCP-1 and Adipocyte Size in Human and Rodent Adipose Tissue

2021 ◽  
Vol 12 ◽  
Author(s):  
María Bové ◽  
Fermi Monto ◽  
Paloma Guillem-Llobat ◽  
M Dolores Ivorra ◽  
M Antonia Noguera ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Stem Cell Differentiation ◽  
Mrna Levels ◽  
Brown Adipocytes ◽  
Peripheral Tissues ◽  
Metabolic Functions ◽  
Neurotrophin 3 ◽  
Isolated Adipocytes

Neurotrophin-3 (NT3), through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (especially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 (encoded by NTF3) was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular, and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC (encoded by NTRK3) and β-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in β-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression.ConclusionsNT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1.

Triiodothyronine amplifies the adrenergic stimulation of uncoupling protein expression in rat brown adipocytes

2000 ◽  
Vol 278 (5) ◽  
pp. E769-E777 ◽  
Author(s):  
Arturo Hernández ◽  
Maria Jesús Obregón
Keyword(s):  
Uncoupling Protein ◽  
Primary Cultures ◽  
Mitochondrial Protein ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Adrenergic Agents ◽  
Brown Adipose ◽  
Mrna Transcripts ◽  
Stimulation Of

Uncoupling protein (UCP), the mitochondrial protein specific to brown adipose tissue, is activated transcriptionally in response to cold and adrenergic agents. We studied the role of triiodothyronine (T3) on the adrenergic stimulation of UCP mRNA expression by use of primary cultures of rat brown adipocytes. Basal UCP mRNA levels are undetectable. Norepinephrine (NE) increases UCP mRNA during differentiation, not during proliferation. In hypothyroid conditions, UCP mRNA response to NE is almost absent. The presence of T3 (0.2–20 nM) greatly increases the adrenergic response (30-fold). The sensitivity of UCP mRNA responses to NE is potentiated ∼100-fold by the presence of T3. The effect is proportional to the dose and time of preexposure to T3. The increases obtained with NE and T3 are prevented by actinomycin and cycloheximide. T3 greatly stabilizes UCP mRNA transcripts. The effects of thyroxine and retinoic acid are weaker than those of T3. In conclusion, in cultured rat brown adipocytes, T3 is required and both synergizes with NE to increase UCP mRNA and stabilizes its mRNA transcripts.

β2-Agonist ritodrine, unlike natural catecholamines, activates thermogenesis prematurely in fetal sheep

1998 ◽  
Vol 275 (1) ◽  
pp. R112-R119 ◽  
Author(s):  
John M. Bassett ◽  
Michael E. Symonds
Keyword(s):  
Fatty Acid ◽  
Fetal Growth ◽  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Nonesterified Fatty Acid ◽  
Adrenergic Agonist ◽  
Fetal Sheep ◽  
Functional Development ◽  
Brown Adipose ◽  
Β2 Agonist

Prolonged administration of the β2-adrenergic agonist ritodrine to fetal sheep increases nonesterified fatty acid mobilization. To investigate whether changes in fetal growth or functional development of brown adipose tissue (BAT) also occur, ritodrine was infused at 5 μg/min iv into eight fetal sheep (6 twins and 2 singletons at 125–128 days of gestation) for 5 days and then at twice this rate for a further 7–11 days. Fetal growth was reduced significantly ( P < 0.02) during ritodrine infusion relative to controls (5.8 ± 17.5 vs. 79.7 ± 10.3 g/day), with growth of skeletal muscles ceasing. Ritodrine reduced perirenal BAT weight by 50% from 18.6 ± 1.89 to 9.3 ± 0.60 g ( P < 0.01) and its lipid content by >70% from 6.5 ± 0.96 to 1.9 ± 0.45 g ( P < 0.01). Mitochondrial protein in BAT was also less ( P < 0.002), but GDP binding to uncoupling protein increased ( P < 0.05). In similar experiments, epinephrine and norepinephrine increased plasma nonesterified fatty acid initially, but neither altered perirenal BAT composition. The β2-adrenergic agonist ritodrine appears able to promote lipid mobilization and thermogenesis in utero.

scholarly journals NT3/TrkC pathway modulates the expression of UCP-1 and adipocyte size in human and murine adipose tissue

2020 ◽  
Author(s):  
María Bové ◽  
Fermi Monto ◽  
Paloma Guillem-Llobat ◽  
M Dolores Ivorra ◽  
M Antonia Noguera ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Stem Cell Differentiation ◽  
Mrna Levels ◽  
Brown Adipocytes ◽  
Peripheral Tissues ◽  
Metabolic Functions ◽  
Reporter Mice ◽  
Isolated Adipocytes

ABSTRACTNT3, through activation of its tropomyosin-related kinase receptor C (TrkC), modulates neuronal survival and neural stem cell differentiation. It is widely distributed in peripheral tissues (specially vessels and pancreas) and this ubiquitous pattern suggests a role for NT3, outside the nervous system and related to metabolic functions. The presence of the NT3/TrkC pathway in the adipose tissue (AT) has never been investigated. Present work studies in human and murine adipose tissue (AT) the presence of elements of the NT3/TrkC pathway and its role on lipolysis and adipocyte differentiation. qRT-PCR and immunoblot indicate that NT3 was present in human retroperitoneal AT and decreases with age. NT3 was also present in rat isolated adipocytes and retroperitoneal, interscapular, perivascular and perirenal AT. Histological analysis evidences that NT3 was mainly present in vessels irrigating AT close associated to sympathetic fibers. Similar mRNA levels of TrkC and β-adrenoceptors were found in all ATs assayed and in isolated adipocytes. NT3, through TrkC activation, exert a mild effect in lipolysis. Addition of NT3 during the differentiation process of human pre-adipocytes resulted in smaller adipocytes and increased uncoupling protein-1 (UCP-1) without changes in β-adrenoceptors. Similarly, transgenic mice with reduced expression of NT3 (Ntf3 knock-in lacZ reporter mice) or lacking endothelial NT3 expression (Ntf3flox1/flox2;Tie2-Cre+/0) displayed enlarged white and brown adipocytes and lower UCP-1 expression.ConclusionsNT3, mainly released by blood vessels, activates TrkC and regulates adipocyte differentiation and browning. Disruption of NT3/TrkC signaling conducts to hypertrophied white and brown adipocytes with reduced expression of the thermogenesis marker UCP-1

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