Adipose tissue and the immune system

Adipocytes anatomically associated with lymph nodes (and omental milky spots) have many special properties including fatty acid composition and the control of lipolysis that equip them to interact locally with lymphoid cells. Lymph node lymphocytes and tissue dendritic cells acquire their fatty acids from the contiguous adipocytes. Lymph node-derived dendritic cells suppress lipolysis in perinodal adipocytes but those that permeate the adipose tissue stimulate lipolysis, especially after minor, local immune stimulation. Inflammation alters the composition of fatty acids incorporated into dendritic cells, and that of node-containing adipose tissue, counteracting the effects of dietary lipids. Thus these specialised adipocytes partially emancipate the immune system from fluctuations in the abundance and composition of dietary lipids. Prolonged, low-level immune stimulation induces the local formation of more adipocytes, especially adjacent to the inflamed lymph node. This mechanism may contribute to hypertrophy of the mesentery and omentum in chronic inflammatory diseases such as HIV-infection, and in smokers. Paracrine interactions between adipose and lymphoid tissues are enhanced by diets rich in n-6 fatty acids and attentuated by fish oils. The latter improve immune function and body conformation in animals and people. The partitioning of adipose tissue in many depots, some specialised for local, paracrine interactions with other tissues, is a fundamental feature of mammals.     

Adipose tissue macrophage in immune regulation of metabolism

The prevalence of obesity and type 2 diabetes is escalating to an epidemic proportion worldwide.Obesity is known to be associated with a state of chronic,low-grade inflammation.Emerging lines of evidence have shown that both innate and adaptive immune responses play crucial roles in the control of metabolic homeostasis.Macrophages in adipose tissues are the essential effector cells in orchestrating metabolic inflammation,which is thought to promote the pathogenic progression of obesity and obesity-related disorders.Here we discuss our current understanding of the distinct modes of activation of adipose tissue macrophages,which can sense the metabolic cues and exert profound effects upon adipose homeostasis.Targeting macrophages in adipose tissues may provide new avenues for developing immunomodulation-based therapeutics against obesity and obesity-associated metabolic diseases.     

Adipose tissue,the immune system and exercise fatigue: how activated lymphocytes compete for lipids

Adipose depots that contain lymph nodes, and probably intermuscular fat in skeletal and cardiac muscle, are specialized to provision adjacent tissue in a paracrine mode. Perinodal adipocytes respond selectively to various cytokines and incorporate proportionately more polyunsaturated fatty acids. Lipolysis in the adipocytes of node-containing depots can be stimulated via inflammation of the enclosed lymph nodes. Repeated immune stimulation elicits properties characteristic of perinodal adipocytes in those elsewhere in the same depot, and hours later in other node-containing depots, but not in nodeless depots. Such site-specific properties of adipose tissue enable partitioning of dietary and metabolic supplies of fatty acids between competing tissues. Local interactions emancipate the peripheral immune system from competing with other tissues for lipids during immune responses, and may be especially important during periods of high demand, such as strenuous exercise. Biopsies of subcutaneous adipose tissue from sites remote from lymph nodes do not adequately represent the composition of fatty acids available to the immune system in situ, and perhaps that supplied to other tissues. Intermuscular fat in skeletal and cardiac muscle may also indicate paracrine relationships between adipocytes and "end-user" tissues. The concept of paracrine interactions between certain adipocytes and "user" tissue may account for the widespread contiguity between these tissues in vivo.     

Adipose tissue houses different subtypes of stem cells

Adipose tissue stromal fraction (ASF) contains multipotent cells capable of differentiation towards several lineages and may be used for the treatment of various degenerative diseases. However, the multipotent cells within ASF have not been fully characterized. In this study we have attempted to characterize stem cells in the ASF obtained through serial dilution. Five single-cell clones were studied. It was found that the single-cell clones exhibited slight but significant differences in proliferative capacity and differentiation potential. We conclude that ASF houses different subtypes of stem cells.     

Adipose tissue engineering with cells in engineered matrices

Tissue engineering has shown promise for the development of constructs to facilitate large volume soft tissue augmentation in reconstructive and cosmetic plastic surgery. This article reviews the key progress to date in the field of adipose tissue engineering. In order to effectively design a soft tissue substitute, it is critical to understand the native tissue environment and function. As such, the basic physiology of adipose tissue is described and the process of adipogenesis is discussed. In this article, we have focused on tissue engineering using a cell-seeded scaffold approach, where engineered extracellular matrix substitutes are seeded with exogenous cells that may contribute to the regenerative response. The strengths and limitations of each of the possible cell sources for adipose tissue engineering, including adipose-derived stem cells, are detailed. We briefly highlight some of the results from the major studies to date, involving a range of synthetic and naturally derived scaffolds. While these studies have shown that adipose tissue regeneration is possible, more research is required to develop optimized constructs that will facilitate safe, predictable and long-term augmentation in clinical applications.Key words: tissue engineering, regenerative medicine, adipose tissue, adipose-derived stem cells, adipogenesis, cell culture, scaffolds, cell-biomaterial interactions     

Adipose tissue engineering with cells in engineered matrices

Tissue engineering has shown promise for the development of constructs to facilitate large volume soft tissue augmentation in reconstructive and cosmetic plastic surgery. This article reviews the key progress to date in the field of adipose tissue engineering. In order to effectively design a soft tissue substitute, it is critical to understand the native tissue environment and function. As such, the basic physiology of adipose tissue is described and the process of adipogenesis is discussed. In this article, we have focused on tissue engineering using a cell-seeded scaffold approach, where engineered extracellular matrix substitutes are seeded with exogenous cells that may contribute to the regenerative response. The strengths and limitations of each of the possible cell sources for adipose tissue engineering, including adipose-derived stem cells, are detailed. We briefly highlight some of the results from the major studies to date, involving a range of synthetic and naturally derived scaffolds. While these studies have shown that adipose tissue regeneration is possible, more research is required to develop optimized constructs that will facilitate safe, predictable, and long-term augmentation in clinical applications.     

Adipose tissue cells, lipotransfer and cancer: A challenge for scientists, oncologists and surgeons

Despite recent evidence of the cancer-promoting role of adipose tissue-derived progenitor and differentiated cells, the use of lipotransfer for tissue/organ reconstruction after surgical removal of cancer is increasing worldwide. Here we discuss in a multidisciplinary fashion the preclinical data connecting obesity, adipose cells and cancer progression, as well as the clinical data concerning safety of lipotransfer procedures in cancer patients. A roadmap towards a more rationale use of lipotransfer in oncology is urgently needed and should include preclinical studies to dissect the roles of different adipose tissue-derived cells, the evaluation of drugs currently candidate to inhibit the interaction between adipose and tumor cells, and carefully designed clinical trials to investigate the safety of lipotransfer procedures in cancer patients.     

Adipose tissue ofDrosophila melanogaster

Summary Using transplantation techniques it was shown that immature and supposedly mature stages of fat body from the larvae ofDrosophila melanogaster do not lyse rapidly in the lytic, internal environment of the young adult. In the younger tissue the protein granules (probably lysosomes) were just beginning to form, whereas in the older tissue the protein granules were at a maximum level. In both cases the implanted tissues became steadily smaller independently of the environment. The decrease in implant size was interreted to mean that the cells were lysing, since the average cell size did not change, and since many cells appear cytologically degenerate. However, the estimated rate of cell loss was much slower than in the case where the cells pass through metamorphosis. Some of the immature cells produced relatively high amounts of protein granules independently of the environment. Although the protein granules are at a maximum amount in both stages, it would appear that additional development must be required for the cells to become susceptible to the lytic environment of the young adult.On leave of absence for 1972–1973: Department of Genetics, University of Nijmegen, The Netherlands.The author expresses gratitude to the National Science Foundation for financial support (Research Grant GB 12969) and to Mrs. Barbara LaTendresse for her expert technical assistance.     

Adipose tissue islets: tissue culture of a potential source of fat cells in the adult rat

Collagenase digests of adipose tissue of the 3 to 4-month-old rat contain groups of 20-100 tightly arranged cells (islets) that copurify with the free-floating fat cells. When cultured along with mature adipocytes the islets give rise to cells, initially fibroblast-like, which rapidly proliferate, acquire lipid droplets, and differentiate into small adipocytes within 4-6 days without the addition to the medium of the agents usually required to produce differentiation in stromal-vascular preadipocytes. Differentiation of these cells is independent of confluence and begins as early as day 2 of culture. The proportion of islet-derived cells that differentiate is directly correlated with the number of mature adipocytes simultaneously present in the culture (r = .709; P less than 0.001). Culture medium exposed to mature adipocytes demonstrated differentiation-promoting activity, suggesting a paracrine effect of these cells. Islets may in vivo constitute a source for newly formed adipocytes in the adult rat. The differentiation of these potential adipocytes may be regulated, at least in part, by the mature fat cells via a paracrine effect.     

Adipose triglyceride lipase in immune response, inflammation, and atherosclerosis

Abstract Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, including macrophages. The hydrolytic cleavage of triacylglycerol by adipose triglyceride lipase (ATGL) generates non-esterified fatty acids, which are subsequently used as essential precursors for lipid and membrane synthesis, mediators in cell signaling processes or as energy substrate in mitochondria. This review summarizes the current knowledge concerning the consequences of ATGL deficiency in macrophages with particular emphasis on macrophage (dys)-function, apoptosis, and atherosclerosis.     

Adipose tissue and cholesterol metabolism

Adipose tissue in man is a major site for cholesterol storage. In obesity over half of total body cholesterol may reside within this tissue; however, relatively little attention has been directed toward understanding the cholesterol metabolism and its relationship to whole body cholesterol homeostasis in this tissue. In this review the factors which influence cholesterol storage are discussed, with particular emphasis on the effects of diet and drug treatment in both animals and man. The uptake, synthesis, and mobilization of adipose tissue cholesterol appears to be mediated and/or regulated, as in other tissues, by the plasma lipoproteins, and these processes are examined with regard to both normal and pathologic states.     

Adipose tissue: a subtle and complex cell system

White adipose tissue (WAT) represents a large amount of all adult tissues. For a long time, it was considered as a poorly active, overgrown and undesirable tissue. It was mainly studied for its involvement in energy metabolism and disorders, as well as for its endocrine functions. WAT is composed of two main populations, matures adipocytes and stroma vascular fraction (SVF) that can be separated easily. The SVF contains two compartments, stromal and hematopoietic that have been recently characterized. The stromal population (or ADAS for Adipose Derived Stromal Cells) presents functional features of, as well as lineage relationship with, macrophages. These stromal cells, that are able to differentiate into adipocytes, also display endothelial potential, and could be considered as vascular progenitors. Differentiation of various adipose-derived cell subsets towards functional cardiomyocytes, osteoblasts, chondrocytes, muscle, hematopoietic and neural cells was also obtained in vitro or in vivo. Adipose tissue thus appears as a complex tissue composed of different cell subsets that could vary according to the nature and the location of fat pads, or to the physiological or pathological status. WAT appears as a very plastic and heterogeneous tissue that is very easy to sample. This represents a great advantage when considering adipose tissue as a potential and suitable source of stem cell for cell therapy. Further investigations in this way have to lead to the emergence of new insights fundamental to progress in our knowledge of adipose tissue biology.     

Adipose tissue is a regulated source of interleukin-10

White adipose tissue (WAT) is the source of pro- and anti-inflammatory cytokines and we have recently shown that this tissue is a major source of the anti-inflammatory interleukin (IL)-1 receptor antagonist (IL-1Ra). We now aimed at identifying additional adipose-derived cytokines, which might serve as regulators of IL-1Ra. We demonstrate here for the first time that the antiinflammatory cytokine IL-10 is secreted by human WAT explants and that it is up-regulated by LPS and TNF-alpha in vitro, as well as in obesity in humans (2- and 6-fold increase in subcutaneous and visceral WAT, respectively) and rodents (4-fold increase).     

Adipose tissue: between the extremes

Adipose tissue represents a critical component in healthy energy homeostasis. It fulfills important roles in whole‐body lipid handling, serves as the body's major energy storage compartment and insulation barrier, and secretes numerous endocrine mediators such as adipokines or lipokines. As a consequence, dysfunction of these processes in adipose tissue compartments is tightly linked to severe metabolic disorders, including obesity, metabolic syndrome, lipodystrophy, and cachexia. While numerous studies have addressed causes and consequences of obesity‐related adipose tissue hypertrophy and hyperplasia for health, critical pathways and mechanisms in (involuntary) adipose tissue loss as well as its systemic metabolic consequences are far less understood. In this review, we discuss the current understanding of conditions of adipose tissue wasting and review microenvironmental determinants of adipocyte (dys)function in related pathophysiologies.     

Adipose tissue protein phosphatase inhibitor-2

Rat fat cells contain three species of spontaneously active inhibitor proteins of protein phosphatase 1, as resolved by SDS-PAGE, with apparent molecular masses of 40 kDa, and 28 kDa respectively. The 33-kDa, thermostable inhibitor was highly purified from bovine adipose tissue and shown to be very similar to inhibitor-2 of skeletal muscle. It was phosphorylated, on threonine only, by glycogen synthase kinase 3. It formed an inactivated complex with protein phosphatase 1, that was reactivated by incubation with ATP-Mg and glycogen synthase kinase 3. By gel filtration it had a Stokes radius of 3.4 nm. Peptide and phosphopeptide maps, generated by Staphylococcus aureus V8 proteinase, trypsin or thermolysin, of the inhibitor and of the skeletal muscle inhibitor-2 were similar. The 40-kDa inhibitor, which was denatured by boiling, represents a novel protein phosphatase inhibitor protein or an undegraded precursor of inhibitor-2. The total activity of inhibitor-2-like material (thermostable and macromolecular) in an adipocyte cytosol extract corresponded to an intracellular concentration of 0.3 microM inhibitor-2.