Brown adipose tissue: Updates in cellular and molecular biology

Brown adipose tissue (BAT) is mainly composed of adipocytes, it is highly vascularized and innervated, and can be activated in adult humans. Brown adipocytes are responsible for performing non-shivering thermogenesis, which is exclusively mediated by uncoupling protein (UCP) -1 (a protein found in the inner mitochondrial membrane), the hallmark of BAT, responsible for the uncoupling of the proton leakage from the ATP production, therefore, generating heat (i.e. thermogenesis). Besides UCP1, other compounds are essential not only to thermogenesis, but also to the proliferation and differentiation of BAT, including peroxisome proliferator-activated receptor (PPAR) family, PPARgamma coactivator 1 (PGC1)-alpha, and PRD1-BF-1-RIZ1 homologous domain protein containing protein (PRDM) -16. The sympathetic nervous system centrally regulates thermogenesis through norepinephrine, which acts on the adrenergic receptors of BAT. This bound leads to the initialization of the many pathways that may activate thermogenesis in acute and/or chronic ways. In summary, this mini-review aims to demonstrate the latest advances in the knowledge of BAT.     

A large‐scale molecular phylogeny of flesh flies (Diptera: Sarcophagidae)

The available data for Sarcophagidae in GenBank were analysed in order to reconstruct the most comprehensive phylogeny to date. GenBank was explored for nine markers that are commonly used in various molecular and phylogenetic studies of flesh flies. We obtained data for 187 species and constructed an aligned dataset with 9241 characters. However, the matrix suffered from 74% missing data due to a low number of sequences for some markers and in most of the cases only short fragments of the analysed genes were available. The reconstructed tree was taxonomically biased towards the subfamilies Paramacronychiinae (12% of the described species) and Sarcophaginae (8.6% of the described species) and specifically the genus Sarcophaga. The third subfamily Miltogramminae was represented by only 0.7% of described species. Moreover, about half of the included species were of forensic importance, while the percentage of such species in the entire family was estimated at 7%. Many nodes had very low support, so in order to increase the support and thereby identify a ‘core topology’, we pruned ‘rogue’ taxa and applied different substitution models. Both strategies improved support considerably, although some nodes still were left unresolved. An analysis of the distribution of bootstrap values across chronograms showed that the weakest phylogenetic signal is restricted to that part of the tree which coincides with the onset of rapid radiations mainly within the genus Sarcophaga. Our study is concordant with phylogenies obtained by other authors, with the most noteworthy exception being the subfamily Paramacronychiinae emerging as paraphyletic with regard to the Miltogramminae, which is in strong conflict with morphological evidence. We discuss the new findings in the light of traditional taxonomical classifications of Sarcophagidae and recent molecular studies.     

A large‐scale molecular survey of Clinostomum (Digenea,Clinostomidae)

Members of the genus Clinostomum Leidy, 1856 are parasites that mature in birds, with occasional reports in humans. Because morphological characters for reliable discrimination of species are lacking, the number of species considered valid has varied by an order of magnitude. In this study, sequences from the DNA barcode region of cytochrome c oxidase I (CO1) and/or internal transcribed spacer (ITS) from specimens from Mexico, Bolivia, Peru, Brazil, Kenya, China and Thailand were analysed together with published sequences from Europe, Africa, Indonesia and North America. Although ITS and CO1 distances among specimens were strongly correlated, distance‐based analysis of each marker yielded different groups. Putative species indicated by CO1 distances were consistent with available morphological identifications, while those indicated by ITS conflicted with morphological identifications in three cases. There was little overlap in sequence variation within and between species, particularly for CO1. Although ITS and CO1 distances tended to increase in specimens that were further apart geographically, this did not impair distance‐based species delineation. Phylogenetic analysis suggests a deep division between clades of Clinostomum inhabiting the New World and Old World, which parallels the distribution of their principal definitive hosts, the Ardeidae.     

Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep

Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-gamma, retinoid-X-receptor-alpha], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 +/- 0.32 kg; control, 5.12 +/- 0.24 kg; P < 0.0001), mean gestational arterial Po(2) (P < 0.0001), plasma glucose (P < 0.01), and insulin concentrations (P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 +/- 0.063; control, 0.741 +/- 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 +/- 0.009; control, 0.115 +/- 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity.     

Aesthetic demand of French seniors: a large‐scale study

doi:10.1111/j.1741‐2358.2009.00331.x
Aesthetic demand of French seniors: a large‐scale study Objectives: The needs of seniors for oral health and aesthetics are growing, as are their demands for aesthetics. This large‐scale study aims to identify the demand for aesthetics for a population aged over 55, and the influence of age and gender. Methods: A 15‐item questionnaire was placed on the web in partnership with a major magazine dedicated to seniors. It reflected practitioners’ questions with regard to senior patient expectations: aesthetic demand assessment, most commonly expressed complaints, the importance given to tooth colour, knowledge of available therapeutic treatments and motivation levels for treatment. Results: The survey generated 3868 responses, 61% from women; 77% of respondents declared being satisfied to very satisfied with their smile. Their highest priority to improve their smile was tooth alignment, followed by their shape, length and shade. Although 60% of respondents were satisfied with their current shading, 53% would prefer to have them whitened. Aesthetic treatments were well‐known to seniors. Over four‐fifths of them had heard of dental implants and ceramic crowns. Two‐thirds of those who wished to improve their smile were considering dental treatment. Conclusion: The high number of collected questionnaires confirms the strong interest shown by seniors for dental aesthetics, particularly from women. Baby‐boomers seem more attentive to the appearance of their smile than their elders. However, the importance of appearance decreases with age, as it becomes less of a priority, with attention more focused on general health.     

Tick‐borne viruses: Current trends in large‐scale viral surveillance

Ticks are ectoparasites that transmit pathogens, such as tick‐borne viruses, to their hosts. Tick‐borne viruses are diverse: they can be categorized into two orders, nine families, and at least 12 genera. Almost 25% of these viruses are infectious to humans and some are a serious threat to public health. The global rise in tick‐borne virus diseases has been linked to climate change which has reduced tick mortality in the winter and extended their active period. The spread of tick‐borne viral diseases to humans has received significant interest due to the increased threat to human life; epidemiological monitoring of tick‐borne viruses using molecular, immunological, and environmental methods is now a priority. Nevertheless, many tick‐borne diseases remain undiagnosed, which poses a challenge to public administration and health care officials. This review discusses three major tick‐borne RNA viruses that cause serious infection in humans: severe fever with thrombocytopenia syndrome (SFTS) virus, tick‐borne encephalitis (TBE), and Crimean–Congo hemorrhagic fever (CCHF) virus. Specifically, we discuss the epidemiological monitoring, vector control measures, molecular diagnostics, vaccines, and environmental determinants related to these viruses. Furthermore, we review the current surveillance of these tick‐borne viruses with a specific focus on diagnostic approaches that employ molecular interventions such as viral nucleic acid isolation, PCR‐based diagnostics, and high‐throughput sequencing technologies.     

Structural and histochemical aspects of perirenal adipose tissue in fetal pigs: relationships between stromal-vascular characteristics and fat cell concentration and enzyme activity

Samples of perirenal adipose tissue were obtained from four fetuses from each of seven crossbred gilts at each of three stages of gestation: 70, 90, and 110 days. Samples were routinely prepared for histochemistry and histology. At each age, the largest fat cell clusters were consistently located near points where large blood vessels entered the loose connective tissue. Cell-cluster size decreased with distance from the entry points of large blood vessels. Fat cells proximal to entry points of large arterioles and fat cells distal to entry points of large arterioles were the same size. Enzyme cytochemistry disclosed that reactions for glucose-6-phosphate dehydrogenase (G6PDH), lipoprotein lipase (LPL) and NADH-TR enzymes were reduced in distal (relative to entry points of large arterioles) adipocytes compared with proximal adipocytes. Reactions for succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH) in adipocytes were not influenced by location within the tissue. Small fat cell clusters with sparse capillary beds surround arterioles in distal areas of sections from fetuses at 70, 90, and 110 days of gestation. In the proximal areas of sections from 110-day-old fetuses, arterioles were surrounded by large fat cell clusters with dense capillary beds. These characteristics serve to distinguish perirenal depots from subcutaneous depots in the fetus.     

An evolutionary theory of large‐scale human warfare: Group‐structured cultural selection

When humans wage war, it is not unusual for battlefields to be strewn with dead warriors. These warriors typically were men in their reproductive prime who, had they not died in battle, might have gone on to father more children. Typically, they are also genetically unrelated to one another. We know of no other animal species in which reproductively capable, genetically unrelated individuals risk their lives in this manner. Because the immense private costs borne by individual warriors create benefits that are shared widely by others in their group, warfare is a stark evolutionary puzzle that is difficult to explain. Although several scholars have posited models of the evolution of human warfare, 1 - 6 these models do not adequately explain how humans solve the problem of collective action in warfare at the evolutionarily novel scale of hundreds of genetically unrelated individuals. We propose that group‐structured cultural selection explains this phenomenon.     

Comparison of sample preparation techniques for large‐scale proteomics

Numerous workflows exist for large‐scale bottom‐up proteomics, many of which achieve exceptional proteome depth. Herein, we evaluated the performance of several commonly used sample preparation techniques for proteomic characterization of HeLa lysates [unfractionated in‐solution digests, SDS‐PAGE coupled with in‐gel digestion, gel‐eluted liquid fraction entrapment electrophoresis (GELFrEE) technology, SCX StageTips and high‐/low‐pH reversed phase fractionation (HpH)]. HpH fractionation was found to be superior in terms of proteome depth (>8400 proteins detected) and fractionation efficiency compared to other techniques. SCX StageTip fractionation required minimal sample handling and was also a substantial improvement over SDS‐PAGE separation and GELFrEE technology. Sequence coverage of the HeLa proteome increased to 38% when combining all workflows, however, total proteins detected improved only slightly to 8710. In summary, HpH fractionation and SCX StageTips are robust techniques and highly suited for complex proteome analysis.     

Offspring polymorphism and bet hedging: a large‐scale,phylogenetic analysis

Offspring polymorphism is a reproductive strategy where individual organisms simultaneously produce offspring that differ in morphology and ecology. It occurs across the Tree of Life but is particularly common among plants, where it is termed seed (diaspore) heteromorphism. The prevalence of this strategy in unpredictably varying environments has resulted in the assumption that it serves as a bet‐hedging mechanism. We found 101 examples of this strategy in southwestern North America. We provide phylogenetically informed evidence for the hypothesis that the occurrence of seed heteromorphism increases with increasing environmental variability, though this pattern was only significant for aridity, one of our two rainfall variability metrics. We provide a strong test of bet hedging for a large, taxonomically diverse set of seed heteromorphic species, lending support to the hypothesis that bet hedging is an important mechanistic driver for the evolution of seed heteromorphism.     

Brown adipose tissue: a scanning electron microscopic study of tissue and cultured adipocytes

The ultrastructure of rat brown adipose tissue (BAT) and of adipocytes cultured from BAT were studied by scanning electron microscopy (SEM). Brown adipocytes in the intact tissue were arranged in lobules with bundles of collagen among them; within each lobule 20- to 40-microns-large adipocytes were packed together. Fibers of reticular collagen enveloped each adipocyte and also connected each cell to vessels and nerves. At the adipocyte surface rounded protrusions were present, which corresponded to the BAT-typical multivacuolar lipid depot. Gradual digestion of the stroma with collagenase disclosed a more delicate, felt-like cover surrounding each adipocyte, probably representing the external lamina of the cell. Complete digestion of the stroma showed a smooth plasmalemma with occasional roundish blebs which varied in size. Cultured (24 h) brown adipocytes from the stromal-vascular fraction of BAT were elongated or polygonal in shape, with a flattened, central nucleus and a number of spherical cytoplasmatic inclusions which have the same dimension and location as lipid droplets. These inclusions were arranged either at cellular poles or around the nucleus; this suggests that brown adipocytes with mature features were present in the culture. Pictures suggesting the detachment of lipid droplets from the cell body were also visible. Lipid droplet extrusion could be a complementary mechanism which might explain the rapid delipidation of brown adipocytes in culture.     

A review of current large‐scale mouse knockout efforts

After the successful completion of the human genome project (HGP), biological research in the postgenome era urgently needs an efficient approach for functional analysis of genes. Utilization of knockout mouse models has been powerful for elucidating the function of genes as well as finding new therapeutic interventions for human diseases. Gene trapping and gene targeting are two independent techniques for making knockout mice from embryonic stem (ES) cells. Gene trapping is high‐throughput, random, and sequence‐tagged while gene targeting enables the knockout of specific genes. It has been about 20 years since the first gene targeting and gene trapping mice were generated. In recent years, new tools have emerged for both gene targeting and gene trapping, and organizations have been formed to knock out genes in the mouse genome using either of the two methods. The knockout mouse project (KOMP) and the international gene trap consortium (IGTC) were initiated to create convenient resources for scientific research worldwide and knock out all the mouse genes. Organizers of KOMP regard it as important as the HGP. Gene targeting methods have changed from conventional gene targeting to high‐throughput conditional gene targeting. The combined advantages of trapping and targeting elements are improving the gene trapping spectrum and gene targeting efficiency. As a newly‐developed insertional mutation system, transposons have some advantages over retrovirus in trapping genes. Emergence of the international knockout mouse consortium (IKMP) is the beginning of a global collaboration to systematically knock out all the genes in the mouse genome for functional genomic research. genesis 48:73–85, 2010. © 2010 Wiley‐Liss, Inc.     

Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology.     

The biology and polymer physics underlying large‐scale chromosome organization

Chromosome large‐scale organization is a beautiful example of the interplay between physics and biology. DNA molecules are polymers and thus belong to the class of molecules for which physicists have developed models and formulated testable hypotheses to understand their arrangement and dynamic properties in solution, based on the principles of polymer physics. Biologists documented and discovered the biochemical basis for the structure, function and dynamic spatial organization of chromosomes in cells. The underlying principles of chromosome organization have recently been revealed in unprecedented detail using high‐resolution chromosome capture technology that can simultaneously detect chromosome contact sites throughout the genome. These independent lines of investigation have now converged on a model in which DNA loops, generated by the loop extrusion mechanism, are the basic organizational and functional units of the chromosome.      

Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance

There is increasing evidence showing that inflammation is an important pathogenic mediator of the development of obesity-induced insulin resistance. It is now generally accepted that tissue-resident immune cells play a major role in the regulation of this obesity-induced inflammation. The roles that adipose tissue (AT)-resident immune cells play have been particularly extensively studied. AT contains most types of immune cells and obesity increases their numbers and activation levels, particularly in AT macrophages (ATMs). Other pro-inflammatory cells found in AT include neutrophils, Th1 CD4 T cells, CD8 T cells, B cells, DCs, and mast cells. However, AT also contains anti-inflammatory cells that counter the pro-inflammatory immune cells that are responsible for the obesity-induced inflammation in this tissue. These anti-inflammatory cells include regulatory CD4 T cells (Tregs), Th2 CD4 T cells, and eosinophils. Hence, AT inflammation is shaped by the regulation of pro- and anti-inflammatory immune cell homeostasis, and obesity skews this balance towards a more pro-inflammatory status. Recent genetic studies revealed several molecules that participate in the development of obesity-induced inflammation and insulin resistance. In this review, the cellular and molecular players that participate in the regulation of obesity-induced inflammation and insulin resistance are discussed, with particular attention being placed on the roles of the cellular players in these pathogeneses. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.