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The article presents medical studies including one on inducing thermogenesis through diet, the development of brown adipose tissue (BAT) and development of brown adipocyte. Topics discussed include background of the studies, how they were conducted and the results. Also presented are the studies on the function of BAT in cold, the use of BAT as an endocrine organ and the association of brown adipocytes with white adipocytes.

In undisturbed Sprague-Dawley rats, with ad libitum access to food and water, body and brain temperatures increase, in association with blood pressure, heart rate, behavioural activity and food intake, approximately every 1-2 hours, and brown adipose tissue (BAT) thermogenesis contributes to the temperature increases (Blessing et al., 2012). Hypothalamic orexin-containing neurons (de Lecea et al., 1998; Sakurai et al., 1998) influence appetite, the sleep-wake cycle, locomotor activity and other physiological variables (Kuwaki, 2011). We have now assessed BRAC-related parameters in conscious unrestrained transgenic (TG) Sprague Dawley rats with ataxin3-mediated destruction of orexin neurons (Beuckmann et al., 2004) in comparison with their wildtype littermates (WT). Under inhaled isoflurane (2% in oxygen) anaesthesia, TG (n=11) and WT (n=9) male rats (300-450 g) were instrumented with chronically implanted thermistors to measure BAT and body temperature (Blessing et al., 2012). All surgical procedures were performed in accord with the Animal Welfare Ethics Committee of Flinders University. Thermistor cables were passed subcutaneously and connected to a headpiece fixed to the skull with dental cement. After one-week recovery the unrestrained TG or WT rats were housed singly in a quiet closed temperature controlled (24-26°C) cage, with ad libitum access to food and water, and with 12 hour dark/light cycling. Behavioural activity was measured with an infrared grid system. Group results (mean ± SEM) were analysed with factorial ANOVA. There was no difference in the timing of the dark active period BRAC-related episodic BAT temperature peaks between TG and WG rats (106±3 min in TG and 111±3 min in WT, p>0.05). However the amplitude of the behavioural activity (7±1 units in TG versus 11±1 units in WT rats, p<0.05) and the increases in BRAC-related BAT temperature (1.22±0.02°C in TG and 1.42±0.03°C in WT, p<0.001) and body temperature (0.80±0.01°C in TG versus 0.90±0.02 in WT, p<0.001) were reduced in the transgenic animals. The difference between BAT and body temperatures was also reduced in the transgenic animals versus the wild type animals (+0.44±0.02°C in TG and +0.55±0.03 °C in WT, p<0.001) suggesting that reduced BAT thermogenesis contributes to the reduced BRAC-related increase in body temperature in transgenic animals. Thus the BRAC organization of daily life does not depend on the function of the orexin-containing neurons, but activity of these neurons contributes to the amplitude of BRAC episodes. Our results suggest that orexin-containing neurons increase the intensity with which rats periodically engage with the external environment. [ABSTRACT FROM AUTHOR]

An abstract of the article "PI3K participates in the estradiol effects on leptin action in the energy homeostasis" by C. M. Melo, B. C. Borges, G. H. Goncalves, F. M. Vechiato, P. M. Rivas, J. Antunes-Rodrigues and L. L. Elias is presented.

Hibernation under extreme cold environment needs a preparation period of some length in which most physiological functions are thought to be remodelled in wide range to adapt to hibernation. Brown adipose tissue (BAT) is an indispensable organ to complete the hibernation behavior, particularly in arousing from hibernation of hypothermia. Taking into consideration the restraint of most physiological functions by low body temperature, remodelling before hibernation occurs possibly in BAT function too. A concrete mechanism of the 'preparation' is still unclear, but the molecular-level remodelling of BAT must be performed during the preparation period of hibernation, because most gene expression stops during deep hibernation. The dominant pathway of BAT thermogenesis occurs through the β3-adrenergic receptor. We investigated the role of the β3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vivo and in vitro. Necessary surgical procedures were carried out under isoflurane anesthesia. Stimulation of BAT by CL316,243 significantly facilitated arousal from hibernation and it also induced arousal in deep hibernating animals, while the β3-antagonist SR59230A inhibited arousal from hibernation. Syrian hamsters in the hibernation group (H) contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group (WA). Although the ability of the β3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between H and WA, its maximum ratio over the basal value at 12°C in H was significantly larger than that in WA. Forskolin, adenylyl cyclase activator, stimulation at 12°C produced equivalent BAT responses in these two groups. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective β3-receptor mechanism at lower temperatures. Hence we hypothesized that the high effectiveness of the receptor mechanism may be due to an increase in number of the receptor that possibly occurs during the preparation period. To investigate the hypothesis, we measured β3-receptor mRNA of BAT removed from animals in 4 stages of activity, WA, CA (cold-acclimated), H and IBA (inter-bout arousal, awake phase during hibernation) by using RT-PCR method. Gene expression of the β3-receptor in BAT of hibernating hamster was significantly smaller by about 40% and 60% than that of WA and CA respectively, but was not different from that of IBA. Results showed that the facilitation of BAT function in hibernating animals may be due to remodelling of the messenger pathway between two molecules, β3-receptor and adenylyl cyclase. [ABSTRACT FROM AUTHOR]

Whereas we earlier thought about the existence of just two different adipose tissues- heat-producing brown and energy-storing white - we now see a much broader spectrum of tissues and cells; - and whereas we earlier thought that brown and white adipose tissues were closely related tissues, as the names imply, we now realize that brown adipose tissue is really developmentally a kind of muscle tissue - and although we do not really know the developmental origin of white adipose tissue, it is clearly not of muscle origin. These different developmental backgrounds are highly reflected in the character of metabolism in the tissues. To this should be added that certain cells (presently called brite or beige) within certain white adipose tissue depots may be able to express the (earlier considered) unique protein of brown adipose tissue: UCP1. The functional significances of the tissues for thermogenesis is strongly related to their ability to express sufficiently high levels of UCP1 to allow them to play a role in systemic metabolism. Whereas the issue of functional significance of the brown and white adipose tissue was earlier an issue mainly of academic interest - as it was thought that brown adipose tissue was not found in adult humans - the present understanding that brown fat exists and is active in adult humans has lifted the issue of the functional significance of the brown adipose tissue to being an enticing and possibly important issue in human metabolic research. [ABSTRACT FROM AUTHOR]

Brown adipose tissue is essential in the newborn to protect against hypothermia through thermogenesis and has a crucial role in energy balance in later life in some animal models. Epicardial and pericardial fat depots have both been shown to possess uncoupling protein 1 (UCP1) and function as brown fat [1,2]. The development and modification of these depots in early life in comparison to classical white adipose tissue has not previously been studied. This study focused on the comparison of epicardial, pericardial and omental fat during early postnatal life through gene expression analysis. UCP1 was analysed as a marker of brown or beige fat capable of thermogenesis. Expression of the white fat markers leptin and adiponectin were investigated to elucidate white adipocyte characteristics of each depot. Peroxisome proliferator-activated receptor (PPAR) gamma is involved in white and brown fat differentiation and was assessed as an indicator of mature adipocyte development. Methods: Four triplet-bearing mothers were entered into the study and a randomly selected triplet was euthanased at 1, 7 or 28 days of age for adipose tissue sampling (n=4 per time point) under Home Office Approval, UK. Pericardial adipose tissue was sampled at 1, 7 and 28 days whereas epicardial and omental adipose tissues were only sampled at 7 and 28 days due to a lack of any observable fat in these depots in 1 day old sheep. RNA was extracted and gene expression analysed by qRT-PCR. Relative mRNA expression was calculated using the GeNorm method corrected to the geometric mean of reference genes IPO8 and RPO, and expressed in arbitrary units [3]. Data are presented as mean ± SEM and analysed using one way ANOVA or unpaired t-Test for comparisons with age. Results: With increasing age, UCP1 expression decreased and the white fat marker leptin increased in all depots studied (see Figure 1). UCP1 was detectable in epicardial and pericardial adipose tissue and, to a lesser extent in omental fat, at 7, but not 28, days of age. Adiponectin also increased up to 28 days which was most pronounced in the pericardial fat depot. PPAR gamma increased significantly in all depots with age. Conclusion: Our study suggests a brown to white fat transformation in all adipose tissues during the first month of postnatal life, even in those depots which are undetectable immediately after birth. This may be accompanied by a loss of brown adipose tissue and increased adipocyte differentiation. [ABSTRACT FROM AUTHOR]

Body and brain temperatures increase when Sprague-Dawley rats explore the external environment, and brown adipose tissue (BAT) thermogenesis contributes to the temperature increases (Ootsuka et al., 2009, Blessing et al., 2012). We have now assessed whether a salient novel environmental event activates BAT thermogenesis. Under inhaled isoflurane (2% in oxygen) anaesthesia, 5 male Sprague-Dawley rats (300-450 g) were instrumented with chronically implanted thermistors to measure BAT and body temperature (Blessing et al., 2012). All surgical procedures were performed in accord with the Animal Welfare Ethics Committee of Flinders University. Thermistor cables were passed subcutaneously and connected to a headpiece fixed to the skull with dental cement. After one-week recovery the unrestrained rats (n=9) were housed singly in a quiet closed temperature controlled (24-26°C) cage. A stocking-mesh bag containing 4 live cockroaches (Periplaneta australasiae) was suddenly introduced into the rat's cage. We recorded BAT and body temperatures for 30 min and then removed the cockroach bag. The rat approached the bag of cockroaches and attempted to bite or rip the stocking-mesh bag. Maximum increases in BAT and body temperatures (mean ± SEM) were recorded and analysed with repeated measures ANOVA. The increase in BAT temperature (1.1±0.16°C) was significantly greater (P<0.05) than the simultaneously measured increase in body temperature (0.76±0.11°C), suggesting that BAT thermogenesis contributes to the increase in body temperature. Our results suggest that brain regulated sympathetically-controlled BAT thermogenesis contributes to the increase in body temperature occurring when the rat is confronted with a novel salient stimulus. [ABSTRACT FROM AUTHOR]