Brown Adipose Tissues in Mammals - Coursework Example

Brown Adipose Tissues in Mammals Introduction In accepted and in conventional definitions of the group of animalsto which human beings belong i.e., the mammals, the capability to nourish their offspring in early stages in a pragmatic manner is the one feature normally encouraged. Besides, this feature is not the only one characteristic that renders the advantage of evolution to mammals. In particular, an exceptional class of tissue exits within mammals, known as BAT or “brown adipose tissue”. It can be said that BAT is a consequence of an individual evolutionary progress that might have occurred quite earlier during the mammalian evolution. The BAT differs from white fat in the way that it generates heat while white fat functions to store energy. Heat is a natural outcome of all kinds of metabolic reactions as it reflects the thermodynamics inefficiency. Hence it can be said that heat is a usual by product of metabolic reactions. However, in brown adipose tissue heat is generated as a major product and therefore it can be regarded as the principal function of this tissue. The broad concern in brown fat contemplates the conception that in mammals, it is the only tissue that is specialized for the generation of heat. BAT and the cardiovascular system Brown adipose Tissue is in a widespread way vascularized, demonstrating a very increased rate of flow of blood throughout peak thermogenesis. Surely, around one third of the output of cardiac muscles can be conducted to the BAT amongst rats adjusted to the cold (Foster and Frydman, 1978), letting the rapid transfer of heat to the core of the body of animal. The increased flow of blood also ascertains that the needed substrates such as oxygen for thermogenesis of fuel are rendered at rates suitable to the main requirements of the tissue (Schrauwen et al., 2012). Structure of BAT The Brown adipose tissue in similarity with the muscles tissues have been regarded as originated from similar stem cells during embryonic stage as they contain the same myogenic factor “Myf5” on their surfaces. Mechanism of Heat Generation in BAT The generation of heat in BAT adopts a unique (seemingly) proton translocation method situated in the inner membrane of mitochondria. This performs as a short circuit of proton throughout the membrane in an attempt to dissipate the proton gradient which is normally yielded during respiration as heat instead of getting associated with the ATP synthesis process. This translocation of proton of mitochondria of brown adipose tissue is determined by a particular uncoupling protein (known as thermogenic) situated within the inner membrane. This UCP or Uncoupling protein, Mr 32-33,000, is acutely regulated so that the heat generated as well as the translocation of protons in the mitochondria vary in accordance with the physiological needs for thermogenesis (Yoneshiro et al., 2012). In reaction to the chronic changes in the needs for thermogenesis, the uncoupling proteins concentration in the mitochondria alters and this is a main method for varying the capability for thermogenesis in brown adipose tissue. For instance, in cold the uncoupling protein concentration enhances while it declines in a warm environment (Foster & Frydman, 1979). Moreover extensive and continuous exposures to a thermogenic signal also consequences in an increment in the total quantity of uncoupling proteins in brown adipose tissue by increasing the mitochondrial content within the tissue, a phenomenon often referred as mitochondriogenesis. By and large, parallel alterations take place in the contents of mitochondria in brown adipose tissue and the particular concentration of uncoupling proteins in the mitochondria. In an acute manner, as mentioned afore, activation of already existing uncoupling proteins takes place and this is usually contemplated in uncloaking of guanosine 5-biphosphate (GDP) attaching locations on the protein. This mitochondrial GDP binding of mitochondria has been extensively employed assay in vitro for measuring the thermogenic activity of the brown adipose tissue. Thus, three distinct procedures exist for the changing thermogenesis in brown adipose tissue. Fatty acids that are unbound render the intracellular stimulus to activate the proton conductivity pathway, by interacting with the uncoupling proteins. Hence a dual function is played by these unbound fatty acids i.e. as a primary stimulus as well as a fuel to activate thermogenesis. The thermogenesis stimulation initiates when the sympathetic nerves discharge nonadrenaline which then in a widespread way innervate brown adipose tissue as this tissue possess a fresh â3−adrenoceptor, which serves as a binding site for nonadrenaline and thus a flow of events start leading to the stimulation of hormone-sensitive lipase along with the lipolysis activation (Xue et al., 2009). Prominent thermogenesis in BAT The conventional role of brown adipose tissue is to produce heat to fulfill thermo regulatory uses (Smith & Horwitz, 1969). As a consequence, a wide range of studies have been done to understand the responses of this tissue when an animal is exposed to low temperatures. In an acute manner, as mentioned above, the mitochondrial translocation of protons that occurs on its inner membrane is enhanced via the stimulation of already existing uncoupling proteins. Extensive exposure to low temperatures thus induces a configuration of alterations in brown adipose tissue. These changes include an enhancement in the number of cells within the tissue, an enhancement in the number of mitochondria as well as an enhancement in the particular UCP concentration in the mitochondria. The overall impact of all these alterations is to extensively enhance the capability for thermogenesis, and all of this process is driven chiefly by an enhanced activation from the sympathetic system. However, a parallel change takes place in other metabolic phenomenon like supplying of substrates (Kikuchi-Utsumi et al, 2002). Cafeteria Diet and BAT The impact on brown adipose tissue of excessive feeding with a palatable and variable ‘cafeteria’ diet comprising of food items for humans has also been a subject of great interest for investigators (Orava et al., 2011). The studies show that such a diet consequences to the activation of a kind of thermogenesis that is induced due to diet. This process renders a counter-regulatory process in the controlling the overall body energy balance in a way that excessive feeding then stimulates energy expenditure while causes a reduction in storage of energy. In experiments done on young animals like mice and rat, it has been observed that upon feeding such a cafeteria diet, the thermogenic capacity as well as thermogenic activity of brown adipose tissue is enhanced. Therefore, in similarity to the consequences of excessive exposure to low temperature, such a diet also initiates with various parallel mechanisms like mitochondrial content, GDP binding of mitochondria and the particular UCP concentration of mitochondria, all are augmented (along with the other measures associated with the activeness of the tissue). Moreover, both of these changes are an outcome of the enhanced sympathetic activation to brown adipose tissue (Vosselman et al., 2013). Further circumstances in which the thermogenic behavior of brown adipose tissue is increased include fever, the awakening from hibernation, and the cachectic condition linked with cancer. These alterations have significant correlates on an entire body grounds in that the entire rate of expenditure of energy and the capability for non-shivering thermogenesis may be enhanced (Cannon and Nedergaard, 2004). Obesity and BAT There are a numerous situations which cause functional or operational atrophy of brown adipose tissue. However, the most extensively studied in this regard is the one associated with obesity. For this particular purpose the functioning of tissue has been examined in a variety of different kinds of obese animals. It has been observed through various studies that a comparative atrophy of the tissue exists in obesity, with a diminution in mitochondrial content, GDP binding in mitochondria, and in the uncoupling proteins concentration. In all these reductions, the foremost reduction occurs in the GDP binding which is then followed by the other two phenomenons. The reduction in thermogenic capacity and thermogenic activity in brown adipose tissue amongst obese mammals imparts considerably to the enhanced energy balance which contributes to the obese condition (Muzik et al., 2013). BAT as a treatment of obesity During the life of an adult human, brown adipose tissue had long been regarded as non functional. This tissue has the capability to generate heat in an attempt to prevent hypothermia on exposure to cold. For this purpose, glucose and fatty acids are being metabolized by brown adipose tissue so that the core temperature of the body is well maintained. However, it is an interesting fact that the mammals having nonfunctional or dysfunctional brown adipose tissue turn obese and acquire dyslipidemia and type II diabetes. This tissue serves as the main spot of adapted thermogenesis that is triggered by sympathetic system during incidence of cold and after unprompted hyperphagia, by that means maintaining the expenditure of energy done by entire body and body fat. Current radionuclide researches have shown the presence of metabolically active brown adipose tissue within the healthy grownup human beings. Upon acute exposure to cold, the human brown adipose tissue is triggered as it is positively correlated to increased expenditure of energy that is induced by cold. Besides, the metabolic functionality of brown adipose tissue is limited in obese and older individuals. The BAT activity is inversely correlated with obesity and this association suggests that due to the energy dissipation function of BAT, it renders protection against the accumulation of large deposits of fats within the body. In reality, either ingesting certain food ingredients on daily basis or reiterated cold exposure act on ephemeral receptor potential conveys employ BAT in linkage with enhanced energy expenditure and diminished body fat in individuals having low BAT functionalities before providing the required treatment (Baron et al., 2012). Hence, BAT provides a therapeutic objective for battling human obesity and associated metabolic issues. Moreover, BAT has been found to have a negative correlation with obesity and that is why obese individuals either don’t have BAT or it is less functional. So by activating BAT, these obese individuals might be treated as this would enhance the energy expenditure (Lichtenbelt et al., 2014). Similarly as mentioned above, the stimulation of thermogenesis consequences from the stimulation of sympathetic system, hence an operational atrophy of brown adipose tissue can be attributed to a decline in the sympathetic tone. Moreover, the regulation of BAT is also dependent upon various factors like glucocotocoids and insulin. These factors have been observed by studying the impacts of artificially induced diabetes (Baba et al., 2007). Conclusion A considerable increase of interest has been seen over the last fifteen years on investigating the biological characteristics of specialized kind of adipose tissue, known as BAT or brown fat or brown adipose tissue. Conventionally, this brown fat has been linked with thermoregulation via its function in the production of heat through non-shivering thermogenesis. The tissue had been prominent in the newborns of several mammalian species, hibernators and the adult rodents who have adapted themselves to the cold atmosphere. The most significant function of the brown adipose tissue has been found to be in nutritional energetic specifically in diet induced-thermogenesis (McAllen et al., 2010). Exploiting the substantial capability of brown adipose tissue (BAT) to deplete energy was initially proposed as a possible objective to curb obesity around forty years ago. The Apparent validity of this approach was, nevertheless, interrogated because of the existing position that human beings. Current authoritative recognition of functional brown adipose tissue in adult human beings as well as a considerable number of crucial developments in the apprehension of the biology of brown fat has reignited concern in this tissue as an anti-obesity objective (Kingwell and Carey, 2013). The activation of Brown adipose tissue enhances the consumption of energy and therefore is continuously investigated to be utilized for the treatment of obesity. The incidence of cold or low temperatures serves as the principal physiological signal for the sympathetic system and brown adipose tissue, as the brown adipose tissue are rendered nerves through sympathetic nervous system. Besides, amongst obese individuals the cold induced stimulation of brown adipose tissue is impaired. In a recent study by Carey et al., (2013) it has been found that brown adipose tissue can be activated by orally administering sympathomimetic ephedrine amongst lean individuals. However, it fails to activate BAT in obese individuals (Carey et al., 2013). References Baba, S., Engles, J. M., Huso, D. L., Ishimori, T. & Wah, R. L. (2007). Comparison of Uptake of Multiple Clinical Radiotracers into Brown Adipose Tissue Under Cold-Stimulated and Nonstimulated Conditions. Journal of Nuclear Medicine. 48:1715–1723 Baron, D. M., Clerte, M., Brouckaert, P., Raher, M. J., Flynn, A. W., Zhang, H., Carter, E. A., Picard, M. H., Bloch, K. D., Buys, E. S. & Scherrer-Crosbie, M. (2012). In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice. Circ Cardiovasc Imaging. 5: 652-9. Cannon and Nedergaard (2004). Brown Adipose Tissue: Function and Physiological Significance. Physiological Reviews. 84: 277–359. Carey, A. L., Formosa, M. F., Van Every, B., Bertovic, D., Eikelis, N., Lambert, G. W., Kalff, V., Duffy, S. J., Cherk, M. H. & Kingwell, B. A. (2013). Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia. 56: 147-55 Foster, D. O. & Frydman, M. L. (1978). Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Canadian Journal of Physiology and Pharmacology 56:110-22. Foster, D. O. & Frydman, M. L. (1979) .Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: the dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis. Canadian Journal of Physiology and Pharmacology 57: 257-70. Kikuchi-Utsumi, K., Gao, B., Ohinata, H., Hashimoto, M., Yamamoto, N. & Kuroshima A. (2002). Enhanced gene expression of endothelial nitric oxide synthase in brown adipose tissue during cold exposure. American Journal of Physiology: Regulatory and Integrative Physiology. 282: R623-6 Kingwell, B. A. & Carey, A. L. (2013). Brown adipose tissue in humans: therapeutic potential to combat obesity. Pharmacol Ther. 140: 26-33. Lichtenbelt, W., Kingma, B., van der Lans, A. & Schellen, L. (2014). Cold exposure – an approach to increasing energy expenditure in humans. Trends in Endocrinology and Medicine. McAllen, R. M., Tanaka, M., Ootsuka, Y. & McKinley, M. J. (2010). Multiple thermoregulatory eVectors with independent central controls. European Journal of Applied Physiology. 109:27–33. Muzik, O., Mangner. T. J., Leonard, W. R., Kumar, A., Janisse, J. & Granneman, J. G. (2013). 15O PET Measurement of Blood Flow and Oxygen Consumption in Cold-Activated Human Brown Fat. J Nucl Med. 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M., Liang, Z., Zhu, Z., Nedergaard, J., Cannon, B. & Cao, Y. (2009). Hypoxia-Independent Angiogenesis in Adipose Tissues during Cold Acclimation. Cell Metabolism. 9, 99–109 Yoneshiro, T., Aita, S., Kawai, Y., Iwanaga, T. & Saito M. (2012). Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr. 95: 845-50 Read More