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There is much interest in brown and beige adipocytes, as their thermogenic activities can suppress weight gain and metabolic disease in rodent models. The authors review recent data that have provided new insights into the development and biology of brown and beige adipocytes and critically assess the possibilities for manipulating these cells to combat obesity and its associated diseases. Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.

يتناول هذا الكتاب سيرة حياة صبري البنا عميل الموساد وتاريخه الإجرامي باغتيال المناضلين الفلسطينيين الشرفاء.. وغيرهم في كل مكان، وتنظيمه الذي انشق عن حركة فتح عام 1974 م. المناضلون في خدمة الموساد ! ! بقلم أحمد رائف، الفصل الأول : قصة جورد، الفصل الثاني : وساوس أبو إياد، الفصل الثالث : صدمات الطفولة، الفصل الرابع : أيلول \"سبتمبر\" الأسود، المدفع والمدفع فقط، الفصل الخامس : صنع في بغداد وغيرها من فصول وموضوعات الكتاب.

Fatty tissue can expand in two ways: through increases in the size of individual adipocytes or through increases in the number of adipocytes. The former process promotes metabolic disease, and the latter protects against it. Merrick et al. used single-cell RNA sequencing to define the hierarchy of mesenchymal progenitor cells that give rise to adipose tissue in mice and humans (see the Perspective by Chau and Cawthorn). They found that progenitor cells expressing a protein called DPP4 give rise to two distinct types of preadipocytes in response to different signals. The DPP4 progenitors reside in a fluid-filled network of collagen and elastin fibers surrounding adipose tissue. In principle, therapeutic interventions that increase progenitor cell differentiation into adipocytes could ameliorate metabolic disease. Science , this issue p. eaav2501 ; see also p. 328 Fat cells arise from multipotent progenitor cells in the reticular interstitium, a recently recognized anatomical niche. Metabolic health depends on the capacity of adipose tissue progenitor cells to undergo de novo adipogenesis. The cellular hierarchy and mechanisms governing adipocyte progenitor differentiation are incompletely understood. Through single-cell RNA sequence analyses, we show that the lineage hierarchy of adipocyte progenitors consists of distinct mesenchymal cell types that are present in both mouse and human adipose tissues. Cells marked by dipeptidyl peptidase–4 (DPP4)/CD26 expression are highly proliferative, multipotent progenitors. During the development of subcutaneous adipose tissue in mice, these progenitor cells give rise to intercellular adhesion molecule–1 (ICAM1)/CD54–expressing (CD54+) committed preadipocytes and a related adipogenic cell population marked by Clec11a and F3 /CD142 expression. Transforming growth factor–β maintains DPP4+ cell identity and inhibits adipogenic commitment of DPP4+ and CD142+ cells. Notably, DPP4+ progenitors reside in the reticular interstitium, a recently appreciated fluid-filled space within and between tissues, including adipose depots.

يعالج كتاب \"الصراع على سورية\" فترة هامة من تاريخ القطر العربي السوري، ويتناول مرحلة الاستقلال حتى قيام الوحدة بين القطرين السوري والمصري، وقد كان مؤلفه من خيرة المؤرخين الغربيين موضوعية حيث قال : إن هذا الكتاب يقوم بتفسير وكشف ماضي بعض المشكلات المعاصرة، وهو لا يحابي أية دولة ولا أي زعيم أو حزب أو مبدأ، كما أنه لا يقف ضد أحد منهم. إن التكتلات السياسية وطبخات الأحزاب والدسائس والمؤمرات التي تهيأ لها أن تجاري أو تعارض الحكم القائم في تلك الفترة، قد كشفها المؤلف في هذا الكتاب بكل تجرد وصدق وأمانة. كما ولج في أحيان كثيرة أبواب مواضيع وحوادث متفرقة، فلما كان رجل الشارع السوري \"بصفة خاصة\" قد أطلع على حقيقة مجراها.

Group 2 innate lymphoid cells are shown to have a critical role in energy homeostasis by producing methionine-enkephalin peptides in response to interleukin 33, thus promoting the beiging of white adipose tissue; increased numbers of beige (also known as brown-like or brite) fat cells in white adipose tissue leads to increased energy expenditure and decreased adiposity. Innate lymphoid cells drive energy up, adiposity down The immune system is now thought to be involved in the development of obesity, together with genetic and environmental factors. Recent research identified group 2 innate lymphoid cells (ILC2s) in adipose tissue as a factor in the development of obesity in mice. David Artis and colleagues show here that ILC2s play a critical role in energy homeostasis by producing methionine-enkephalin peptides in response to interleukin-33. This promotes the emergence of beige adipocytes, a specialized adipocyte population arising from white adipose tissue. This 'beiging' process leads to increased energy expenditure and decreased adiposity. Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity 1 , 2 . Group 2 innate lymphoid cells (ILC2s) can regulate adaptive immunity 3 , 4 and eosinophil and alternatively activated macrophage responses 5 , and were recently identified in murine white adipose tissue (WAT) 5 where they may act to limit the development of obesity 6 . However, ILC2s have not been identified in human adipose tissue, and the mechanisms by which ILC2s regulate metabolic homeostasis remain unknown. Here we identify ILC2s in human WAT and demonstrate that decreased ILC2 responses in WAT are a conserved characteristic of obesity in humans and mice. Interleukin (IL)-33 was found to be critical for the maintenance of ILC2s in WAT and in limiting adiposity in mice by increasing caloric expenditure. This was associated with recruitment of uncoupling protein 1 (UCP1) + beige adipocytes in WAT, a process known as beiging or browning that regulates caloric expenditure 7 , 8 , 9 . IL-33-induced beiging was dependent on ILC2s, and IL-33 treatment or transfer of IL-33-elicited ILC2s was sufficient to drive beiging independently of the adaptive immune system, eosinophils or IL-4 receptor signalling. We found that ILC2s produce methionine-enkephalin peptides that can act directly on adipocytes to upregulate Ucp1 expression in vitro and that promote beiging in vivo . Collectively, these studies indicate that, in addition to responding to infection or tissue damage, ILC2s can regulate adipose function and metabolic homeostasis in part via production of enkephalin peptides that elicit beiging.

يدور موضوع هذا الكتاب حول نشوء الشرق الأوسط الحديث. يقدم باتريك سيل هذه القصة عبر سرد حياة رياض الصلح، السياسي اللبناني الذي تحول إلى رجل الدولة العربي المبرز في زمانه، واستمر حتى اغتياله في العام 1951، وكان في طليعة الأحداث والكفاح الذي أسس للوضع الحالي في المنطقة، حيث انتزع استقلال لبنان من فرنسا وأصبح رئيس وزرائه الأول لمرحلة ما بعد الاستقلال، مع جميع تحديات ومآسي تلك المرحلة. إنه كتاب مبهر يربط تاريخ الكفاح العربي من أجل الاستقلال ربطا مباشرا بحياة الشخصيات المعنية، مستعينا على ذلك بالسجلات العثمانية والبريطانية والفرنسية، وعلى مقابلات عدة. إنه مرجع قيم للدارسين والباحثين، يحمل أهمية مؤثرة لكل من يحاول أن يتعرف أكثر على منطقة ودول الشرق الأوسط.

Significance High levels of brown/beige fat activity protects animals against metabolic disease, but there has been little known about the precursor cells that mediate the expansion of brown or beige fat. We discovered that early B-cell factor 2 (Ebf2), a transcription factor, is selectively expressed in brown and beige fat cell precursors. Through purification of Ebf2 ⁺ cells, we identified a gene profile of brown fat precursors that can be used to distinguish these cells from other developmentally related cell types. Importantly, Ebf2 was also found to regulate the gene expression profile of brown fat precursor cells. Taken together, this study identifies Ebf2 as a highly specific marker of brown and beige preadipose cells and reveals that Ebf2 functions to control brown preadipose cell identity. Brown adipocytes and muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to platelet-derived growth factor α ⁺, myogenic factor 5 Cʳᵉ-lineage–marked cells. RNA-sequence analysis identified early B-cell factor 2 ( Ebf2 ) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2 -expressing cells purified from Ebf2 ᴳFᴾ embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2 -expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2 expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells.

يدور موضوع هذا الكتاب حول نشوء الشرق الأوسط الحديث. يقدم باتريك سيل هذه القصة عبر سرد حياة رياض الصلح، السياسي اللبناني الذي تحول إلى رجل الدولة العربي المبرز في زمانه، واستمر حتى اغتياله في العام 1951، وكان في طليعة الأحداث والكفاح الذي أسس للوضع الحالي في المنطقة، حيث انتزع استقلال لبنان من فرنسا وأصبح رئيس وزرائه الأول لمرحلة ما بعد الاستقلال، مع جميع تحديات ومآسي تلك المرحلة. إنه كتاب مبهر يربط تاريخ الكفاح العربي من أجل الاستقلال ربطا مباشرا بحياة الشخصيات المعنية، مستعينا على ذلك بالسجلات العثمانية والبريطانية والفرنسية، وعلى مقابلات عدة. إنه مرجع قيم للدارسين والباحثين، يحمل أهمية مؤثرة لكل من يحاول أن يتعرف أكثر على منطقة ودول الشرق الأوسط.

Key Points Brown and beige adipocytes are thermogenic fat cells that are highly specialized in dissipating chemical energy in the form of heat. There is great hope that these cells can be targeted therapeutically to combat obesity, insulin resistance and type 2 diabetes. Brown adipocytes develop in distinctive developmental depots of brown adipose tissue (BAT) and have a relatively stable thermogenic phenotype. These cells are poised for heat production in response to various stimuli, including catecholamines that are secreted by sympathetic nerves in BAT on cold exposure. Beige adipocytes are uncoupling protein 1 (UCP1)-expressing and thermogenically competent adipocytes that form in white adipose tissue (WAT) depots in response to various stimuli, including cold exposure or β3-adrenergic agonists. The beige phenotype of WAT is flexible, and the maintenance of beige cells requires ongoing stimulation. Beige adipocytes can arise from adipogenic precursor cells in WAT through de novo differentiation or through the direct conversion of mature unilocular white-like adipocytes. Brown and beige fat cells express certain transcription factors, such as early B-cell factor 2 (EBF2), PR domain zinc finger protein 16 (PRDM16), interferon regulatory factor 4 (IRF4) and zinc finger protein 516 (ZFP516), that cooperate with the general adipogenic factors peroxisome proliferator-activated receptor-γ (PPARγ) and the CCAAT/enhancer-binding proteins (C/EBPs) to drive brown adipocyte differentiation and thermogenic gene programming. ZFP423 acts in white adipocytes to suppress EBF2 and maintain white fat fate. Type 2 cytokine signalling and alternative macrophage activation play a crucial part in regulating both brown fat thermogenesis and beige fat biogenesis. Alternatively activated macrophages secrete catecholamines in WAT to promote browning. Brown adipocytes (which reside in brown adipose tissue) and beige adipocytes (which develop in white adipose tissue in response to cold) expend energy to produce heat and are therefore important in regulating body temperature and body weight. Recent studies provide insights into the developmental origins of brown and beige adipocytes and into the regulation of their differentiation and function. Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight. Brown adipocytes develop in discrete and relatively homogenous depots of brown adipose tissue, whereas beige adipocytes are induced to develop in white adipose tissue in response to certain stimuli — notably, exposure to cold. Fate-mapping analyses have identified progenitor populations that give rise to brown and beige fat cells, and have revealed unanticipated cell-lineage relationships between vascular smooth muscle cells and beige adipocytes, and between skeletal muscle cells and brown fat. In addition, non-adipocyte cells in adipose tissue, including neurons, blood vessel-associated cells and immune cells, have crucial roles in regulating the differentiation and function of brown and beige fat.