Metabolomics analysis reveals potential response mechanisms to cold stress in Altay sheep.

Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small‐animal PET/MRI and the novel radioligand [18F]‐AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice. Pharmacological inactivation of PDE10A with the highly selective inhibitor MP‐10 recruited BAT and potentiated thermogenesis in vivo. In diet‐induced obese mice, chronic administration of MP‐10 caused weight loss associated with increased energy expenditure, browning of white adipose tissue, and improved insulin sensitivity. Analysis of human PET data further revealed marked levels of PDE10A in the supraclavicular region where brown/beige adipocytes are clustered in adults. Finally, the inhibition of PDE10A with MP‐10 stimulated thermogenic gene expression in human brown adipocytes and induced browning of human white adipocytes. Collectively, our findings highlight a novel thermoregulatory role for PDE10A in mouse and human adipocytes and promote PDE10A inhibitors as promising candidates for the treatment of obesity and diabetes.

The relationship between increased body mass index and risk for diabetes mellitus or cardiovascular disease is well established. Such observations have driven considerable interest into the nature of adipose tissue and what mechanisms might help explain how adipose tissue and specific aspects of adipocyte biology influence cardiometabolic disorders. For example, adipocytes are now recognized as a source of mediators released into the circulation, like the adipokines resistin and adiponectin, which can modulate inflammation, insulin sensitivity, and atherosclerosis. Other molecules released from adipocytes like free fatty acids and reactive oxygen species can also exert both local and distant effects that may be integral to the development of diabetes mellitus, atherosclerosis, and their complications. To an increasing extent, adipose tissue is now understood as an organ playing important physiological and pathological roles. Both the absence of fat, as with certain lipodystrophies, and excess adiposity are associated with diabetes mellitus, with mechanisms that appear to include infiltration of inflammatory cells into adipose tissue and the release of systemic mediators. Article see p 1067 To these and the many other adipocyte actions that continue to be uncovered, recent work has added another critical dimension to our evolving view of fat: the specific location of a given adipose depot. Subcutaneous white fat, visceral white fat, brown fat, epicardial fat, and perivascular fat—including fat around the coronaries, the thoracic aorta, and the abdominal aorta—have all been identified as distinct depots that exert unique local and systemic effects (Table). These issues are of particular interest given studies. suggesting that brown adipose tissue (BAT), which drives thermogenesis, is variably present in humans, associated with decreased adiposity, and may be a therapeutic target. In this issue of Circulation , Chang and colleagues add to this still emerging picture by providing the intriguing observation that a deficiency of peroxisome proliferator-activated …

Physiological responses to cold and starvation stresses in the liver of yellow drum (Nibea albiflora) revealed by LC-MS metabolomics.

It is unusual to re-visit a paper a half-century after first reading it, as I have done with the classic publication of Per Scholander, Raymond Hock, Vladimir Walters and Lawrence Irving published in The Biological Bulletin in 1950 (Scholander et al., 1950). My first reading of this paper, and others by Scholander and colleagues on temperature adaptation in aquatic and terrestrial ectotherms (Scholander et al., 1953; Scholander et al., 1957), occurred around 1962, early in my doctoral studies when I trekked to Antarctica to study cold adaptation in fish. These papers provided much of the conceptual and empirical foundation for the work I anticipated doing with notothenioid fishes. My interests in polar birds and mammals at that time were largely confined to their roles as photographic subjects. However, my reading of the 1950 Biological Bulletin paper turned out to be highly important in broadening my scientific horizons and helping me to formulate a perspective on evolutionary adaptation to temperature that spanned the full range of biological (body) temperatures and the adaptive patterns observed among all taxa, whether endothermic or ectothermic. A fresh reading of this paper by scientists of my generation and, even more, a first reading by scientists whose parents may not have been born when the paper first appeared, still has much to offer in teaching us about thermal biology and how scientific research in comparative and evolutionary physiology has evolved.The studies of thermal biology by Scholander and colleagues that were initiated shortly after the end of World War II and conducted with major logistical support from the US military helped in important ways to define the evolutionary strategies used by endothermic homeotherms – mammals and birds – to cope with differences in ambient temperature. Importantly, the focus of these initial studies was on evolutionary adaptation, not phenotypic acclimation or acclimatization to cold, phenomena that later took center stage in analysis of thermal biology in endotherms. The 1950 paper was one in a series from this group that elucidated the roles of what they termed three possible ‘avenues for cold adaptation’ in mammals and birds: variations in the body-to-air thermal gradient, insulation level and basal metabolic rate. In other words, how were heat production and heat exchange altered to allow mammals and birds to maintain a stable and high body temperature? The previous papers by these authors, plus earlier literature cited in the 1950 paper, led to the tentative conclusion that adaptive changes in body temperature to reduce the body-to-air thermal gradient and, thereby, reduce heat flux between animal and environment, are unlikely to play a role in cold adaptation in active adult mammals and birds. To quote the 1950 paper, ‘…there are no signs so far that body temperature of mammals and birds is adaptive to the different climates on earth.’ This well-buttressed conclusion leads to another – and yet unanswered – set of questions: What is the basis for selection of temperatures near 37–40°C for avian and mammalian core body temperatures? Is there something special about this particular range of temperatures? If so, what is it?The remaining two ‘avenues for cold adaptation’ had also been partially explored in earlier studies by Scholander and colleagues. It was clear from their work and that of others that insulation played a critical role. As stated in the 1950 paper, ‘…we established, by insulation measurements, the general rule that arctic mammals have warmer furs than do tropical mammals.’ However, this adaptive mechanism, while of importance, could not at that time be regarded as offering the full story. The final ‘avenue for cold adaptation’, the role of evolved temperature-adaptive differences in basal metabolic rate, remained a possible mechanism of cold adaptation, with animals from cold polar environments possibly exhibiting higher metabolic rates per unit mass than animals from warmer temperate locations. Most existing basal metabolic rate data were from studies on temperate species; there was not an adequate diversity of environments represented in these data sets to fully evaluate whether basal metabolic rates reflected evolutionary thermal history. To resolve this issue, it was necessary to conduct additional studies of mammals and birds from thermal environments that were as different as possible in terms of maximal temperature. Thus the dual focus – Arctic versus tropical – of the studies presented in the 1950 paper. The metabolic rate measurements made with endemic species from Point Barrow, Alaska, and Barro Colorado Island in the Central American tropics essentially put the final nail in the coffin of this potential mechanism of adaptation to cold. The metabolic rate measurements presented in the 1950 paper were made with animals spanning a wide range of sizes and rate measurements were made as closely as possible under ‘resting’ or ‘basal’ conditions and in the absence of acute cold stress. Appropriately, the data gathered by Scholander et al. were analyzed in the context of Francis Benedict's famous ‘mouse to elephant’ relationship of metabolic scaling (Benedict, 1938). The results of these experiments seemed unambiguous: ‘…we may state as a tentative generalization that the basal metabolic rate of terrestrial mammals from tropics to arctic is fundamentally determined by a size relation according to the formula Cal./day = 70 kg3/4 and is phylogenetically nonadaptive to external temperature conditions. Equally nonadaptive is the body temperature, and the phylogenetic adaptation to cold therefore rests entirely upon the plasticity of the factors which determine the heat loss, mainly the fur insulation.’ Thus, natural selection seemed not to have packed more metabolic capacity into a gram of an arctic mammal than into a gram of a similar-sized tropical mammal. At least this seemed to be the case when analyses involved normothermic adult animals, such as those used by Scholander et al. However, as the caveat in the above quotation (‘tentative generalization’) seems to hint, later work showed that there was more to the story.As is the case of many foundational papers, observations and comments made in the 1950 paper seem prescient when examined in the context of what has subsequently been discovered. One such comment is the brief mention that a small mammal, the arctic weasel, showed an extraordinarily high rate of heat production when exposed to cold; this species' metabolic rate was well above the regression line of the ‘mouse to elephant’ curve. Scholander et al. remarked that it seemed ‘somewhat odd’ that the weasel didn't simply increase its insulation when exposed to cold. This ‘oddity’ and similar observations on other small, cold-stressed mammals helped to pave the way for the discovery of the thermogenic role of brown adipose tissue (BAT) (Cannon and Nedergaard, 2004; Smith, 1961). The discovery of this specialized heat-generating tissue casts metabolic adaptation to cold by mammals (no avian equivalent of BAT is known) in a new light. The importance of heat generation by BAT is arguably the most significant extension of our understanding of thermal biology in mammals made since the 1950 paper was published. I'd like to think that the ‘oddity’ noted by Scholander and colleagues puzzled readers enough to catalyze a deeper look at non-basal metabolic capacities, namely those of BAT, the one type of thermogenic tissue known in mammals.A second easily missed point in the 1950 paper is one that is not explicitly indicated by the paper's title. In addition to addressing the adaptations required to withstand cold, Scholander et al. pay heed to the challenges faced by tropical mammals and birds. Thus they state, ‘It seems then that the problem for tropical mammals is neither overheating nor cooling, but, actually, both.’ Moreover, the authors emphasize (presciently, as things are turning out) that, ‘Many parts of the tropics are so hot and humid that a few degrees’ rise in the temperature would mean death for mammals and birds because they cannot adapt to it by raising their body temperatures.' My re-examination of this paper over 50 years since first reading it was done in concert with the appearance in 2010 of articles by Sherwood and Huber and McMichael and Dear that dealt with this threat to low latitude mammals and birds, a danger that would have seemed completely ‘academic’ back in 1950 when concerns about global warming – an expression that seems to have been introduced to the scientific literature only in 1975 in a classic paper by Wallace Broecker in Science (Broecker, 1975) – were still well off in the future (Sherwood and Huber, 2010; McMichael and Dear, 2010). In their analysis of the capacities of birds and mammals to cope with the combination of rising temperatures and humidity, these authors build on (but, regrettably, do not cite) the types of studies found in the 1950 classic by Scholander et al. The 2010 papers point out that, as the need for effective evaporative cooling becomes more critical in a warming world, capacities to evaporate water from the body surfaces becomes increasingly challenging. The basic physics of the situation shows that, when wet bulb temperatures (TW) exceed 35°C, evaporative dissipation of metabolic heat by mammals and birds ceases to be possible. How close are we to this situation of ‘melt down’, the exclusion of habitats from occupancy by endothermic homeotherms due to TW values >35°C? Currently, TW never exceeds 31°C, even in the hottest climates (Sherwood and Huber, 2010). However, TW is predicted to rise with global mean temperature at a ratio of 3°C for every 4°C of global warming. The models used to predict rates of global warming offer a range of estimates and are typically limited for extrapolating trends beyond the current century. However, as Sherwood and Huber emphasize, using models based on realistic assumptions about release of greenhouse gases and extending these models beyond 2100, within two or three centuries the temperatures of some regions may increase by ~7°C and, therefore, have combinations of heat and humidity that result in TW near 35°C. Because such a large fraction of the human population resides at low latitudes, Sherwood and Huber conjecture that global warming of 11–12°C would lead to intolerable values of TW in the regions where most of the human population is currently found (Sherwood and Huber, 2010). Moreover, these low latitude regions are zones where the greatest biodiversity is commonly found. The early studies of Scholander and colleagues help to put into sharp relief the challenges faced by endothermic homeotherms in confronting rising temperatures and humidity. Birds and mammals are ‘stuck’, evolutionarily, with high mass-specific metabolic (heat generation) rates. It seems inconceivable that they can evolve a physiological solution that would allow them to cope with the threats posed by TW values greater than 35°C.In summary, reading (or re-reading) this classic paper offers a number of rewards. First, in terms of its primary question about fundamental evolutionary strategies for cold adaptation, we can come to appreciate how the principal ‘avenue’ taken by birds and mammals for maintaining high and stable body temperatures regardless of ambient temperature was elucidated. Second, we find a nice example of how an experimental ‘oddity’ can lead to further work that, in this case, helped open up the broad field of BAT physiology. Third, and certainly without the intention of the authors, the paper has provided a valuable context for evaluating the challenges posed to endothermic homeotherms by global climate change. And, lastly, there are rewards from (re)visiting this work that deal less with specific scientific discoveries than with the ways in which doing science have evolved. These lessons seem especially valuable for younger scientists for whom the practice of reading literature that is more than a year or two old may not exist. In our (usually futile) obsession to stay on top of the current literature, the classics of the past – the formative publications that built the foundation for our field – are too often neglected or just downright forgotten entirely. As Sydney Brenner recently commented, ‘…most scientists are too busy working in the present and thinking anxiously about the future and have no time to view their work in the context of what has gone before’ (Brenner, 2012). Disregarding the past is a shame, for several reasons. One is that, by neglecting the foundational literature of one's field, one is apt to lack an appreciation of how the shaping principles (‘paradigms’) of one's discipline have originated and subsequently evolved. Another benefit of examining the older literature is to get a sense of how different it was to do science at a time when major questions were first being addressed experimentally. For comparative physiology, the first two or three decades after World War II were an era of both intellectual and geographical explorations of exciting new territory. These were halcyon days when opening up entirely new lines of study could be done with simple instruments, minimal needs for costly reagents, and, therefore, relatively tiny budgets (with the exception of travel costs for exploring distant and exotic lands). And, as the working and writing styles of early, intrepid explorers of comparative physiology such as Per Scholander and his collaborators, Knut Schmidt-Nielsen, and others suggest, doing research was probably a lot more fun and adventurous back then. Writing could be a bit more colorful too, compared with the prose found in the space-limited pages of contemporary journals. Can you think of a recent paper in which there occurs something equivalent to a statement that the sample size was low because the sled dogs ate one-third of the fish that were caught (Scholander et al., 1957)? In these incredibly busy times, it is worthwhile to pause, read some of the classics and contemplate what life was like back in the days when the ratio of novelty of discovery to grant dollars expended was arguably relatively high compared with the present. Classic papers such as those published by Scholander and colleagues over a half-century ago give their readers a clear sense of not only how the foundational discoveries of our field were made, but also of the adventure that was associated with these early intellectual and geographical explorations. Having been his faculty colleague for two decades, I think I can safely say that when Per Scholander chose the title for his autobiography, Enjoying a Life in Science (Scholander, 1990), he was at once giving an honest summary of a great career and challenging his readers to follow an example that, while increasingly tough to meet, should still be our goal.

The perirenal adipose tissue is the main depot in newborn goats, and it has recently been shown to represent functional fat [l]. In the rat, brown adipose tissue contains a high activity of the iodothyronine 5'deiodinase enzyme system which converts thyroxine to the active thyroid hormone, 3,3',5-triiodothyronine [see 21. Iodothyronine 5'deiodinase exists in two major forms, termed types I and 11. The type I contains a selenocysteine residue at the active site, and both enzyme activity and enzyme protein are highly sensitive to deficiency of the trace element selenium [3.4]. Although the type I1 enzyme does not contain selenocysteine, its activity is also decreased in selenium deficiency [4]. The iodothyronine 5'deiodinase in rat brown adipose tissue, which is rapidly induced on cold exposure of the animal, appears to be exclusively of the type I1 form [see 2.31. High iodothyronine 5'-deiodinase activity has been reported in brown of neonatal lambs, cattle, and rabbits, but the form of the enzyme varies in these species. Only the type I has been reported in newborn cattle [5], while both types I and I1 are present in lambs and rabbits with type I predominating in the former, and type I1 in the latter [6,7]. In the present study we have determined the iodothyronine Sdeiodinase activity of the perirenal adipose tissue of newborn goats, and examined the changes in activity during the transition of the tissue from brown to white fat. We were particularly concerned to establish the type of iodothyronine Sdeiodiase present, and whether this varies during early postnatal development. Such information is important for assessing the likely impact of selenium deficiency on brown thermogenesis and cold responsiveness in neonatal agricultural animals. Male goats, British Saanen breed, were obtained from the Rowett herd, within 12 h of birth, and at 2.5,5,7, 14 and 21 days of age (2-4 goats each). Adipose tissues were removed from five sites: perirenal, pericardial, omental, and subcutaneous (hind limb and neck regions) although only the perirenal tissue was used in the present study. The tissues were frozen in liquid nitrogen, and stored at -80°C. After thawing, the tissues were homogenized in a sucrose/HEPES/dithiothreitol buffer, pH 7.0, and centrifuged at 80 xg for 10 min at 4°C. as described previously [2]. The infranatant was collected, and stored at -70°C until required for analysis. The total iodothyronine 5'deiodinase activity was subsequently measured at 37°C. as previously [2]. High total iodothyronine 5'deiodmase activity was found in perirenal adipose tissue of newborn goats, indicating that the tissue has a substantial capacity for the conversion of thyroxine to 3.3'5-t~iiiodothyronine at birth (Table 1). The activity remained high over the first 5 days of life, but fell progressively thereafter. By 3 weeks of age the total activity (per g of tissue) was only 2% of that in the newborn (Table 1). Propylthiouracil inhibition studies showed that the major portion (-70 80%) of the total activity was due to the seleniumcontaining type I form, the remainder being type 11. Although iodothyronine 5'-deiodinase activity in the perirenal pad fell markedly over the first 3 weeks of postnatal life, the relative proportion of types I and I1 remained essentially constant. Table 1. Developmental changes in iodothyronine 5'deiodinase activity in goat penrenal adipose tissue

Brown adipose tissue expends energy in the form of heat via the mitochondrial uncoupling protein UCP1. Recent studies showed that brown adipose tissue is present in adult humans and may be exploited for its anti-obesity and anti-diabetes actions. Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism. Here, we report that apelin-APJ signaling promotes brown adipocyte differentiation by increasing the expressions of brown adipogenic and thermogenic transcriptional factors via the PI3K/Akt and AMPK signaling pathways. It is also found that apelin relieves the TNFα inhibition on brown adipogenesis. In addition, apelin increases the basal activity of brown adipocytes, as evidenced by the increased PGC1α and UCP1 expressions, mitochondrial biogenesis, and oxygen consumption. Finally, we provide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristics in white adipocytes. This study, for the first time, reveals the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to combat obesity and related metabolic disorders.

Adipose Acyl-CoA Synthetase-1 Directs Fatty Acids toward β-Oxidation and Is Required for Cold Thermogenesis

Adipose tissue represents an organ that is highly dynamic and contributes toward vital survival events such as immune responses, lactation, metabolism fuel, and thermogenesis. Data emerging from recent studies support the notion of adipose tissue being organized into a complex system characterized by a discrete anatomy, elevated physiological plasticity, and specific vascular and nerve supplies. Vasoactive intestinal peptide (VIP), along with its receptors, type 1 (VPAC1) and type 2 (VPAC2), has been implicated in various physiological and pathophysiological processes. However, studies on VIP and its receptors in adipose tissue are limited. To explore VIP's presence and activity, as well as its adipose tissue-based receptors, we conducted a study on isolated adipocytes and adipose tissue from inguinal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT) in normal and cold-stressed rats. Our findings indicate the presence of the gene expression VIP and VPAC1 in both WAT and BAT under normal conditions, while VPAC2 was absent. In both WAT and BAT, cold exposure upregulated VIP gene expression. However, the response of VIP receptors to cold exposure is controversial. VPAC2 gene expression was induced in both WAT and BAT, while VPAC1 gene expression presented no change of significance in BAT and a slight reduction in WAT. Additionally, VIP, VPAC1, and VPAC2 proteins were identified from Western blot studies on white and brown adipocytes. After exposure to cold there was an increase of significance in the VIP, VPAC1, and VPAC2 protein levels. This study provides novel insights into how VIP and its receptors alter gene expression and protein levels in adipose tissue and adipocytes during cold stress, indicating their potential involvement in adipose tissue regulation. The findings propose VIP's potentially crucial role in adipose tissue's adaptation to cold stress by affecting the metabolic and biochemical functions of subcutaneous and interscapular adipocytes, with potentially significant implications in the context of developing therapies targeting metabolic disorders.

We hypothesized that maternal low or high nutrition would give unique effects to morphological and molecular dynamics in adipose tissue of fetus of fatty breed Wagyu (Japanese Black) cattle which produce highly marbled beef. This study aimed to determine the effects of maternal energy intake in Wagyu cows, during gestation on fetal adipose tissue development, histochemical properties, and gene and microRNA (miRNA) expression. Cows were allocated to one of two nutritional energy groups: 120% (HIGH) or 60% nutritional requirements of (LOW). Fetuses (n = 6 per treatment) were removed from pregnant cows by cesarean section at fetal age 260 ± 8 days and euthanized. Subcutaneous adipose tissue (SAT), thoracic cavity visceral adipose tissue (TVAT), and perirenal adipose tissue (PAT) were collected for analysis. In histochemical analysis, in SAT and PAT, HIGH fetuses had greater diameter of adipocytes than LOW fetuses (P<0.05). Only in SAT, LOW fetuses had more Leptin (LEP) mRNA and tended to have more Peroxisome Proliferator-Activated Receptor gamma (PPARG) CCAAT-enhancer-binding proteins alpha (CEBPA) and Glucose transporter (GLUT) 4 mRNA(P<0.10). In all SAT, TVAT, and PAT, LOW fetuses had higher levels of the brown adipose tissue (BAT) biomarkers Uncoupling Protein (UCP) 1 and PPARG coactivator (PGC) 1α mRNA than HIGH fetuses (P<0.08). Meanwhile, in the other adipose tissue, LOW fetuses had lower PPARG, CEBPA, and Zinc Finger Protein (ZFP) 423 (in TVAT and PAT), FASN (in TVAT), LEP and GLUT4 mRNA (in PAT; P<0.10). In particular, in TVAT and PAT, LOW fetuses exhibited lower expression of WAT biomarkers (PPARG and ZFP423). Differential expression of various miRNAs related to adipogenesis between the LOW and HIGH fetuses was detected in an adipose tissue-specific manner (P<0.10). Based on adipose tissue-specific effects of maternal nutrition, these findings suggested that poor maternal nutrition in Wagyu cattle increased BAT development in SAT, TVAT and PAT, while elevated maternal nutrition stimulated fetal SAT development compared with that of TVAT and PAT.

Development changes in the content of the mitochondrial-uncoupling protein (UCP) have been studied in adipose depots of bovine fetuses and a newborn calf as well as in adipose depots of newborn and aging lambs. The occurrence of UCP unique to brown adipose tissue (BAT) was investigated by GDP binding, photoaffinity labeling with 8-azidoadenosine 5'-triphosphate, and immunoblots using specific antibodies directed against rat UCP. A protein of 32,000 relative molecular weight was characterized in both species with properties similar to those of rodent UCP. In bovine, UCP became detectable in the perirenal adipose tissue at day -80 and its content increased until birth. Both in bovine (perirenal, subscapular, and retroperitoneal sites) and in ovine (perirenal, subscapular, retroperitoneal, and pericardiac sites), all adipose tissues except the subcutaneous adipose tissue contained at birth UCP and thus can be considered as BAT. The data indicate that the perirenal adipose depot should play in bovine and ovine a major thermogenic role at birth, whereas perirenal and pericardiac adipose tissues of lambs held under cold conditions for 45 days after birth did not show any immunoreactive UCP.

Ability to express uncoupling protein (UCP) and establish UCP-dependent thermogenesis was analyzed in anatomical areas of mice that are generally considered to be white adipose tissue: mesenterial, perimetral, epididymal, inguinal, and superficial layer of interscapular white adipose tissue. The mice were acclimatized for 1 week to 4 degrees C; the following week they were exposed to cold stress (1 h at -20 degrees C, 2-3 times daily). In such conditions in inguinal adipose tissue, slot-blot analysis detected significant amount of UCP mRNA and lipoprotein lipase mRNA. Immuno-electron-microscopic localization of UCP showed that developed mitochondria of cold-stressed inguinal adipocytes contained UCP in the same amount as uncoupled (UC)-mitochondria of brown adipocytes. Morphological and morphometrical analysis showed that such inguinal adipose tissue appeared as brown adipose tissue. Since in control mice, inguinal adipose tissue was UCP-negative and tissue appeared as white adipose tissue, the duration of this white-to-brown adipose tissue conversion was analyzed. Mice, cold stressed for 1 week, were rewarmed at 28 degrees C and their inguinal adipose tissue was analyzed in comparison with interscapular brown adipose tissue and epididymal white adipose tissue for another 37 days. During that time inguinal adipocytes ceased expressing UCP mRNA; UC-mitochondria in inguinal adipocytes were destroyed and replaced with common, C-mitochondria; and UCP was undetectable immunohistochemically. Adipocytes accumulated lipids, and the tissue morphologically once again resembled white adipose tissue. Described changes showed that besides typical brown and white adipose tissue in mice, there existed a third type of adipose tissue described as convertible adipose tissue.

Adipose tissue produces both vascular growth factors and inhibitors. Since obesity is associated with expansion of the capillary bed in regional adipose depots the balance between these factors may favor angiogenesis. White and brown adipose tissues (WAT and BAT) plasticity, namely the ability to expand, plays a critical role in the regulation of body energy balance. as a thermogenic organ, the activity of BAT counteracts the obesity. BAT possesses extraordinarily complex vascular networks to support its high thermogenic activity. It also meets the needs of supplying oxygen and substrates to fuel thermogenesis and distributing heat throughout the body rapidly. Brown adipose tissue is related to thermogenesis while white adipose tissue is the shape of storage of high‐calorie foods. The temperature conditions, when normal and above, cause a decrease in the activity of brown adipose tissue which plays a role in the regulation of body temperature while the nutrients are collected as adipocytes instead of being consumed as heat. Therefore, in this study, we aimed to compare the differences in angiogenic/antiangiogenic factor levels in normal and obese rats due to cold application and to investigate possible changes in brown adipose tissue due to the application of cold stress. Vascular endothelial growth factor (VEGF), matrix metalloproteinase II (MMP‐II), hypoxia inducible factor 1α (HIF1‐α), angiostatin ve endostatin concentrations were measured in brown adipose tissue (BAT) and white adipose tissue (WAT) from 12 control (6 rats kept in room temperature, 6 rats kept in 10 °C for 72 h) and 12 obese (6 rats kept in room temperature and 6 rats kept in 10 °C for 72 h). All animals were 6 months old. In our the study, vascular endothelial growth factor (VEGF), matrix metalloproteinase‐II, hypoxia inducible factor 1α, angiostatin and endostatin levels were investigated. While angiogenic factors increased in cold stress application in control animals, antiangiogenic factors decreased. Angiogenic factors decreased due to cold stress application and increased in antiangiogenic factors in obese animals. Antiangiogenic factors were found to be increased in brown adipose tissue and angiogenic factors increased in white adipose tissue. It was observed that the increase in antiangiogenic factors was more evident in brown fat tissue of obese rats exposed to cold stress. In addition to nutritional conditions, it is concluded that the temperature conditions of the body are effective on angiogenic/antiangiogenic factors and may be effective on brown fat tissue which plays a role in thermogenesis. It should be evaulated that increased levels of antiangiogenic factors are in obese rats may contribute to reducing adipose tissue activity in cope with obesity.Support or Funding InformationThis research was funded by Inonu University, Department of Scientific Research Projects Project No: FYL‐2018‐943).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Morphology and biochemical properties of perirenal adipose tissue from lamb ( Ovis aries). A comparison with brown adipose tissue

Objective: Obesity, the disease of our age, is a condition that occurs when there is an excess of fat tissue in the body. It is not merely a concern about weight gain, but rather a medical issue that elevates the risk of various diseases including heart disease, diabetes, high blood pressure, and certain cancers. This study aimed to explore the impact of a high-fat diet under normal conditions and cold stress, as well as the influence of propolis as a dietary supplement, on vascular endothelial growth factor (VEGF) and endostatin levels in rats fed with propolis. Material and Methods: Thirty-six 3-month-old female Wistar rats (6 rats in each group) sourced from Inonu University Experimental Animal Production and Research Center were utilized for the study. Propolis was administered by gavage, dissolved in water, at a dosage of 2 mL per day for two weeks. Results: The group exhibiting at least a 20% increase in weight due to high-fat diet consumption was categorized as the obese group. Tissues including heart, liver, lung, brown adipose, and white adipose tissues were procured from the obese, propolis-treated, and control groups. Endostatin and vascular endothelial growth factor levels were assessed in the tissues using the ELISA method. The study revealed an elevation in VEGF levels in brown adipose tissue in both cold stress and propolis treatment groups, accompanied by a reduction in white adipose tissue compared to the control group. Additionally, VEGF levels displayed a general increase in lung, liver, and heart tissues. Conversely, endostatin levels, an antiangiogenic factor, decreased in brown adipose tissue while increasing in white adipose tissue. In liver, lung, and heart tissues, endostatin levels exhibited a general decrease. Conclusion: The findings suggest that both cold stress and propolis treatment influence VEGF and endostatin levels in various rat tissues, indicating potential implications for obesity-related conditions and angiogenesis regulation.

Ontogenetical changes in adipose tissue of the cat: Convertible adipose tissue