Brown adipose tissue

Tissue expression Mainly white and brown adipose tissue weak expression in liver, muscle, gut, macrophages, pancreatic (3-cells and haemopoietic tissues... 

Tissue-Specific Expression. In the adult rodent, PPARy is expressed in brown and white adipose tissue, and at lower levels in intestine, retina, skeletal muscle, and lymphoid organs. In human, PPARy is most abundantly expressed in white adipose tissue and at lower levels in skeletal muscle, the heart, and liver, but not in lymphoid tissues, although PPARy has been identified in macrophages in human atheromas. 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

Brown adipose tissue is the site of nonshivering thermogenesis. It is found in hibernating and newborn animals and is present in small quantity in humans. Thermogenesis results from the presence of an uncouphng protein, thermogenin, in the inner mitochondrial membrane. 

Various authors Brown adipose tissue—role in nutritional energetics. (Symposium.) ProcNutrSoc 1989 48 165. 

Beta-1, beta-2, and beta-3 adrenergic receptors are G-protein-coupled receptors. Beta-1 and beta-2 receptors mediate the positive inotropic, chronotropic, and dro-motropic effects of the endogenous catecholamines epinephrine and norepinephrine. The beta-3 subtype seems to play a role in regulating thermogenesis and lipid mobilization in brown and white adipose tissue. Several coding and promoter polymorphisms of these receptors have been identified. Clinical studies in asthma... 

The major types of adipose tissue are (1) white adipose tissue, which manufactures, stores, and releases lipid and (2) brown adipose tissue, which dissipates energy via uncoupled mitochondrial respiration. Obesity research includes evaluation of the activity of adrenergic receptors and their effect on adipose tissue with respect to energy storage and expenditure or thermogenesis. 

Thiolester hydrolases are present in most tissues and cell compartments. High concentrations are found in liver microsomes and in brown adipose tissue mitochondria and peroxisomes. Several acyl-CoA hydrolases have shown a close relationship to the nonspecific carboxylesterases EC 3.1.1.1. Thus, palmitoyl-CoA hydrolase purified from rat liver microsomes was found to be identical to esterase pI 6.2I6A (ES4 type). An acyl-CoA hydrolase was isolated that showed high similarity to esterase pI 6.1 [74a] [129] [130]. These few examples are further illustrations of the unsatisfying situation of the traditional classification of esterases. 

Khat produces sympathomimetic effects, increasing heart rate and blood pressure. When khat is chewed, the increases are gradual, maximizing at about 2 hours and lasting for 4 hours. However, tolerance develops to blood pressure and heart rate effects in habitual users. Mydriasis and increases in respiration also occur. Cathinone induces thermogenesis in brown adipose tissue, which is mediated by jS-adrenergic receptors (Tariq et al. 1989). 

Because the rate of the ETC increases, with no ATP synthesis, energy is released as heat. Important uncouplers include 2,4-dinitrophenol (2,4-DNP) and aspirin (and other salicylates). Brown adipose tissue contains a natural uncoupling protein (UCP, formerly called thernio-genin), which allows energy loss as heat to maintain a basal temperature around the kidneys, neck, breastplate, and scapulae in newborns. 

High concentrations of radioactivity were observed in body fat and livers of rats, mice, and squirrel monkeys given oral doses of 60 mg/kg " C-labeled chloroform (Brown et al. 1974a). The maximum levels of radioactivity in the blood appeared within 1 hour and were 3 pg equivalents chloroform/mL for mice and 10 pg equivalents chloroform/mL for monkeys, which represented -0.35 and 1%, respectively, of the total radioactivity. In monkeys, bile concentrations peaked within 6 hours. The distribution of radioactively labeled chloroform was studied in three strains of mice (Taylor et al. 1974). No strain-related differences were observed however, higher levels of radioactivity were found in the renal cortex of males and in the liver of females. The renal binding of radioactive metabolites may have been altered by variations in the testosterone levels as a result of hormonal pretreatment in females or castration in males. Sex-linked differences in chloroform distribution were not observed in rats or monkeys (Brown et al. 1974a). Chloroform accumulates in the adipose tissue of rats after oral exposure of intermediate duration (Pfaffenberger et al. 1980). 

Electron micrograph of brown adipose tissue. Kindly by Dr Caroline Pond of the Open University, UK. 

It is localised mainly in the dorsal part of the thorax under the shoulder blades, along the spinal cord and around the adrenal glands so that it is close to the vital tissues and organs. These can therefore be rapidly warmed by increased activity in brown adipose tissue. 

There is discussion as to whether brown adipose tissue in humans can play a role in body weight control by oxidising fat fuels and converting the chemical energy into heat. 

The rate of electron transfer in isolated mitochondria from brown adipose tissue, in the absence of ADP and phosphate, is high indicating that the mitochondria are uncoupled (see Appendix 9.9). 

The activity of the ATP synthase is low in comparison with that in mitochondria from other tissues i.e. mitochondria in brown adipose tissue can generate very little ATP. 

The first in vivo evidence for the involvement of this tissue in heat production was obtained from experiments on hibernating animals. Thermocouples were placed within brown adipose tissue during arousal from hibernation the... 

In order to provide heat when it is required to maintain or increase body temperature, a mechanism must exist for the regulation of the activity of this uncoupling protein. The mechanism has been established by following the principles described in Chapter 3. The properties of the uncoupling protein are studied using mitochondria isolated from brown adipose tissue in vitro (as described in Appendix 9.9). 

The properties are as follows, (i) The activity of the protein (i.e. the inward transport of protons) is inhibited by ATP. (ii) The activity of the protein is increased by the presence of long-chain fatty acids, since they relieve the ATP inhibition, (iii) When mitochondria, isolated from brown adipose tissue, are incubated in the presence of fatty acids, there is a sharp increase in the rates of electron transfer, substrate utilisation and oxygen consumption, whereas the rate of ATP generation remains low. These studies indicate that the rate of proton transport, by the uncoupling protein, depends on the balance between the concentrations of ATP and fatty acids, (iv) In adipocytes isolated from brown adipose tissue, the rate of oxygen consumption (i.e. electron transfer) is increased in the presence of catecholamines. 

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