Brown Adipose Tissue Regulates Small Artery Function Through NADPH Oxidase 4–Derived Hydrogen Peroxide and Redox-Sensitive Protein Kinase G-1α

During cytochemical studies of brown adipose tissue from rat, cytoplasmic organelles that apparently show peroxidative activity have been observed. The majority of the organelles have a diameter of 0.1-0.8 µ and a finely granular homogeneous matrix and are delimited by a single unit membrane. No sign of a "crystalloid" was seen. In order to demonstrate the peroxidative activity of the peroxisomal enzyme catalase in the organelles, brown adipose tissue was incubated in a medium containing 3,3'-diaminobenzidine tetrahydrochloride, after prefixation in 3% glutaraldehyde. The activity was blocked by 3-amino-l,2,4-triazole (an inhibitor of catalase) but not by KCN. Omission of exogenous hydrogen peroxide did not inhibit the reaction in the organelles. It is concluded that rat brown adipose tissue contains peroxisomes and, since the abundance of these organelles varies according to the physiologic activity of the tissue, peroxisomes may have a role in the thermogenic metabolism of brown fat.

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Cyclic GMP and cyclic GMP-dependent protein kinase in brown adipose tissue of developing rats

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/0304-4165(79)90295-2 ◽

1979 ◽

Vol 582 (1) ◽

pp. 122-131 ◽

Cited By ~ 10

Author(s):

J SKALA ◽

B KNIGHT

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Brown Adipose Tissue ◽

Cyclic Gmp ◽

Dependent Protein Kinase ◽

Brown Adipose ◽

Dependent Protein

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Nicotine Improves Obesity and Hepatic Steatosis and ER Stress in Diet-Induced Obese Male Rats

Endocrinology ◽

10.1210/en.2013-1839 ◽

2014 ◽

Vol 155 (5) ◽

pp. 1679-1689 ◽

Cited By ~ 57

Author(s):

Patricia Seoane-Collazo ◽

Pablo B. Martínez de Morentin ◽

Johan Fernø ◽

Carlos Diéguez ◽

Rubén Nogueiras ◽

...

Keyword(s):

Nervous System ◽

Body Weight ◽

Adipose Tissue ◽

Energy Balance ◽

Protein Kinase ◽

Brown Adipose Tissue ◽

Male Rats ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Amp Activated Protein Kinase

Nicotine, the main addictive component of tobacco, promotes body weight reduction in humans and rodents. Recent evidence has suggested that nicotine acts in the central nervous system to modulate energy balance. Specifically, nicotine modulates hypothalamic AMP-activated protein kinase to decrease feeding and to increase brown adipose tissue thermogenesis through the sympathetic nervous system, leading to weight loss. Of note, most of this evidence has been obtained in animal models fed with normal diet or low-fat diet (LFD). However, its effectiveness in obese models remains elusive. Because obesity causes resistance towards many factors involved in energy homeostasis, the aim of this study has been to compare the effect of nicotine in a diet-induced obese (DIO) model, namely rats fed a high-fat diet, with rats fed a LFD. Our data show that chronic peripheral nicotine treatment reduced body weight by decreasing food intake and increasing brown adipose tissue thermogenesis in both LFD and DIO rats. This overall negative energy balance was associated to decreased activation of hypothalamic AMP-activated protein kinase in both models. Furthermore, nicotine improved serum lipid profile, decreased insulin serum levels, as well as reduced steatosis, inflammation, and endoplasmic reticulum stress in the liver of DIO rats but not in LFD rats. Overall, this evidence suggests that nicotine diminishes body weight and improves metabolic disorders linked to DIO and might offer a clear-cut strategy to develop new therapeutic approaches against obesity and its metabolic complications.

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β-Lapachone Regulates Obesity through Modulating Thermogenesis in Brown Adipose Tissue and Adipocytes: Role of AMPK Signaling Pathway

The American Journal of Chinese Medicine ◽

10.1142/s0192415x19500423 ◽

2019 ◽

Vol 47 (04) ◽

pp. 803-822 ◽

Cited By ~ 4

Author(s):

Hyun Jeong Kwak ◽

Mi-Young Jeong ◽

Jae-Young Um ◽

Jinbong Park

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Brown Adipose Tissue ◽

Signaling Pathway ◽

Uncoupling Protein ◽

Therapeutic Implication ◽

Mitogen Activated Protein Kinase ◽

Ampk Signaling ◽

Compound C ◽

Brown Adipose

Activation of brown adipose tissue (BAT) has been proposed as a promising target against obesity due to its increased capacity for thermogenesis. In this study, we explored the effect of [Formula: see text]-Lapachone ([Formula: see text]L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of [Formula: see text]L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr[Formula: see text] mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). In addition, [Formula: see text]L elevated thermogenic proteins including uncoupling protein 1 (UCP1) and mitochondrial count in BAT and human adipose tissue-derived mesenchymal stem cells (hAMSCs). [Formula: see text]L also induced AMP-activated protein kinase (AMPK) phosphorylation, subsequent upregulation of acetyl-CoA carboxylase (ACC) and UCP1, and these effects were diminished by AMPK inhibitor compound C, suggesting that AMPK underlies the effects of [Formula: see text]L. Mitogen-activated protein kinase pathways participated in the thermogenesis of [Formula: see text]L, specifically p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated by [Formula: see text]L treatment in hAMSCs. Additionally, inhibitors of p38/JNK/ERK1/2 abrogated the activity of [Formula: see text]L. Taken together, [Formula: see text]L exerts anti-obese effects by inducing thermogenesis mediated by AMPK signaling pathway, suggesting that [Formula: see text]L may have a potential therapeutic implication of obesity. Taken together, [Formula: see text]L exerts anti-obese effects by not only inducing thermogenesis on brown adipocytes but also inducing the browning of white adipocytes. The anti-obese effect of [Formula: see text]L is mediated by AMPK signaling pathway, suggesting that [Formula: see text]L may have potential therapeutic implication of obesity.

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cAMP-dependent protein kinase from brown adipose tissue: temperature effects on kinetic properties and enzyme role in hibernating ground squirrels

Journal of Comparative Physiology B ◽

10.1007/s003600050172 ◽

1998 ◽

Vol 168 (7) ◽

pp. 513-525 ◽

Cited By ~ 30

Author(s):

J. A. MacDonald ◽

K. B. Storey

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Brown Adipose Tissue ◽

Temperature Effects ◽

Ground Squirrels ◽

Tissue Temperature ◽

Kinetic Properties ◽

Dependent Protein Kinase ◽

Brown Adipose ◽

Dependent Protein

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Adenosine 3′,5′-cyclic phosphate, lipolysis and oxygen consumption in brown adipose tissue from newborn rabbits effect of cervical sympathectomy and of noradrenalin and theophylline in vitro, and the partial purification of an adenosine 3′,5′-cyclic phosphate-dependent protein kinase

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/0304-4165(74)90093-2 ◽

1974 ◽

Vol 343 (2) ◽

pp. 287-296 ◽

Cited By ~ 16

Author(s):

B.L. Knight

Keyword(s):

Adipose Tissue ◽

Oxygen Consumption ◽

Protein Kinase ◽

Brown Adipose Tissue ◽

Partial Purification ◽

Dependent Protein Kinase ◽

Brown Adipose ◽

Dependent Protein ◽

Cyclic Phosphate

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Protein kinases in brown adipose tissue of developing rats: substrate specificities, separation, and changes in activity during development

Canadian Journal of Biochemistry ◽

10.1139/o78-134 ◽

1978 ◽

Vol 56 (9) ◽

pp. 869-874 ◽

Cited By ~ 1

Author(s):

Josef P. Skala ◽

Brian L. Knight

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Brown Adipose Tissue ◽

Kinase Activity ◽

Specific Activity ◽

Brown Fat ◽

Supernatant Fraction ◽

Protein Kinase Activity ◽

Nonhistone Proteins ◽

Brown Adipose

Protein kinase activity in the 100 000 × g supernatant fraction of brown adipose tissue was assayed with various proteins as substrates. Greatest activity was obtained with histone subfraction f2b and the lowest activity with protamine. cAMP stimulated the phosphorylation of histones but not that of the other proteins. The specific activity of protein kinase in brown fat of rats changed during infancy, and the pattern of changes was different with different protein substrates.Electrophoresis of the tissue-soluble extract gave nine major bands of protein kinase activity. These were assayed on the gels under the optimal conditions for each substrate. Five of the bands were histone kinases and gave little activity with nonhistone proteins. Two bands gave their greatest activity with phosvitin or casein. Protamine and arginine-rich histone were particularly good substrates for the two remaining bands. The activity in each band exhibited a different and distinct pattern of ontogenic development, which was not affected by the nature of the protein used for the assay. There was a reasonable similarity between the overall developmental profile for the rate of phosphorylation of each substrate calculated from the sum of activities determined on the individual bands and the profile directly determined in the whole soluble fraction.Both the direct assay and the electrophoretic results indicate that brown fat contains a number of protein kinase activities that can be distinguished by their specificities for protein substrate and by the pattern of changes in their activities during development. There were three main patterns of ontogenic changes in activity: one decreased progressively from high values in late foetuses; the second showed a marked fall in activity during the 3rd week after birth; and in the third, the activity rose after birth and then remained constant. The greatest changes in kinase activity thus occur during the periods when there are pronounced changes in the rates of proliferation and differentiation in brown fat, in its capacity to produce heat, and in the diet of the animal. It seems possible that the different types of protein kinase carry out phosphorylations involved in the regulation of different processes in brown fat.

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A protein kinase inhibitor in brown adipose tissue of developing rats

Biochemical Journal ◽

10.1042/bj1380195 ◽

1974 ◽

Vol 138 (2) ◽

pp. 195-199 ◽

Cited By ~ 21

Author(s):

Josef P. Skala ◽

George I. Drummond ◽

Peter Hahn

Keyword(s):

Adipose Tissue ◽

Protein Kinase ◽

Cyclic Amp ◽

Brown Adipose Tissue ◽

Inhibitory Activity ◽

Kinase Inhibitor ◽

Protein Kinase Inhibitor ◽

Supernatant Fraction ◽

Brown Adipose ◽

Tissue Homogenates

A heat-stable protein was extracted from brown adipose tissue of infant rats that inhibited both purified bovine heart protein kinase and a crude preparation of protein kinase from brown fat. It did not act as an adenosine triphosphatase nor did it exert its effect by proteolytic action. Inhibition of protein kinase was affected in both the presence and the absence of cyclic AMP. Most of the inhibitory activity was present in the 100000g supernatant fraction of tissue homogenates. Inhibitory activity was highest perinatally and it declined 10 days after birth. It is suggested that the protein kinase inhibitor may play a role in regulating cyclic AMP actions.

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