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Biomedical subjects

C M Pond

Publications and source records attributed to C M Pond.

At least 19 recordsLinked to original sources

What are subcutaneous adipocytes really good for?

Our acute awareness of the cosmetic, psychosocial and sexual importance of subcutaneous adipose tissue contrasts dramatically with how poorly we have understood the biology of this massive, enigmatic, often ignored and much-abused skin compartment. Therefore, it is timely to recall the exciting, steadily growing, yet underappreciated body of evidence that subcutaneous adipocytes are so much more than just 'fat guys', hanging around passively to conspire, at most, against your desperate attempts to maintain ideal weight. Although the subcutis, quantitatively, tends to represent the dominant architectural component of human skin, conventional wisdom confines its biological key functions to those of energy storage, physical buffer, thermoregulation and thermoinsulation. However, already the distribution of human superficial adipose tissue, by itself, questions how justified the popular belief is that 'skin fat' (which actually may be more diverse than often assumed) serves primarily thermoinsulatory purposes. And although the metabolic complications of obesity are well appreciated, our understanding of how exactly subcutaneous adipocytes contribute to extracutaneous disease - and even influence important immune and brain functions! - is far from complete. The increasing insights recently won into subcutaneous adipose tissue as a cytokine depot that regulates innate immunity and cell growth exemplarily serve to illustrate the vast open research expanses that remain to be fully explored in the subcutis. The following public debate carries you from the evolutionary origins and the key functional purposes of adipose tissue, via adipose-derived stem cells and adipokines straight to the neuroendocrine, immunomodulatory and central nervous effects of signals that originate in the subcutis - perhaps, the most underestimated tissue of the human body. The editors are confident that, at the end, you shall agree: No basic scientist and no doctor with a serious interest in skin, and hardly anyone else in the life sciences, can afford to ignore the subcutaneous adipocyte - beyond its ample impact on beauty, benessence and body mass.

Adipocytes↗

Changes in lymphokine receptor expression and fatty acid composition of phospholipids and triacylglycerols in rat adipocytes associated with lymph nodes following a transient immune challenge.

Single-photon counting fluorimetry was used to record the time course of the expression of interleukin-10 receptors labelled with fluorescent antibodies on the surface of adipocytes over 24h, following an immune challenge to the rat popliteal lymph node. Homologous perinodal and remote-from-node samples from the stimulated and unstimulated popliteal depots were compared in rats fed on plain chow and chow supplemented with 10% w/w suet, fish or vegetable oils. Receptor expression was maximal 6 h after stimulation, and returned to baseline after 24 h, and was similar in the stimulated and unstimulated depots. Fewer receptors were elicited in tissues from rats fed lipid-supplemented diets compared with the control diet, with fewest of all following the fish oil diet. These data suggest that interleukin-10 is involved in local interactions between perinodal adipocytes and lymph node lymphoid cells. Both triacylglycerols and phospholipids contained more polyunsaturates and fewer saturates in perinodal adipose tissue than in samples from sites not associated with lymphoid tissue. These data are consistent with paracrine interactions between perinodal adipocytes and activated lymphoid cells.

Adipocytes↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

Long-term changes in adipose tissue in human disease.

Redistribution of white adipose tissue is a long-term symptom of several chronic diseases. Although the roles of adipocytes in acute illness have been thoroughly studied, how or why short-term responses of adipose tissue to disease sometimes produce long-term redistribution, and the causal relationship between the anatomical changes and the associated metabolic syndromes are poorly understood. The present paper reviews explanations for the redistribution of adipose tissue after infection with HIV, and in Crohn's disease; both conditions that share the peculiarity of selective expansion of certain adipose depots while others are depleted. HIV adipose tissue redistribution syndrome (HARS) develops gradually after several months of infection with the HIV both in untreated patients and in those taking protease inhibitors and nucleoside reverse transcriptase inhibitors. Some current theories about the causes of HARS are critically assessed, and reasons presented for implicating local interactions between the immune system and perinodal adipocytes. Some evolutionary aspects of conspicuous long-term changes in the distribution of human adipose tissue are discussed. Adipose tissue acts as a social signal, indicating dietary history and previous exposure to pathogens. A distinctive symptom of Crohn's disease is selective enlargement of the mesenteric adipose tissue near the diseased lymph nodes and intestine. Perinodal adipocytes have site-specific properties not found in adipocytes from nodeless depots, such as perirenal and epididymal, that may equip them to interact locally with lymph-node lymphoid cells, making polyunsaturated fatty acids selectively and rapidly available to activated immune cells. Studies of the time course of activation of perinodal adipocytes via the lymph nodes they enclose indicate that prolonged or frequent stimulation recruits more adipocytes to control by immune cells, which may lead to selective enlargement of node-containing depots. These concepts suggest hypotheses about HARS and the anomalous development of mesenteric adipose tissue in Crohn's disease that could form the basis for further investigations.

Adipose Tissue↗

Adipose tissue: quartermaster to the lymph node garrisons.

Why is mammalian adipose tissue always split into a few large depots and many small ones, widely scattered around the body? Recent research suggests that fat cells (adipocytes) in the minor depots that enclose lymph nodes could be specialised to supply immune cells with the fuel and materials they need to mount a prompt, effective response to foreign invasion. Eliminating them or disrupting their relationship with immune cells may have unforeseen consequences.

Adipose Tissue↗

Interactions of noradrenalin and tumour necrosis factor alpha, interleukin 4 and interleukin 6 in the control of lipolysis from adipocytes around lymph nodes.

The contributions of inflammatory and immunosuppressive cytokines and noradrenalin to the control of lipolysis in adipocytes surrounding and remote from lymph nodes were investigated in healthy adult guinea-pigs. A few hours after excision from fasting animals, spontaneous lipolysis in adipocytes from around the popliteal and mesenteric lymph nodes and omental "milky spots" was significantly lower than in those from elsewhere in the same depots, and much lower than in perirenal, epididymal or parametrial adipocytes. The perinodal adipocytes were consistently more sensitive to noradrenalin at 10(-8), 10(-7)and 10(-5) M, and their maximum rate of lipolysis was higher. They also responded more strongly to pre-incubation for 24 h with tumour necrosis factor alpha interleukin 6 and interleukin 4 than those elsewhere in the same depots. Tumour necrosis factor alpha and interleukin 6 applied alone stimulated lipolysis, but combined with interleukin 4, they suppressed glycerol release, especially in perinodal adipocytes, thereby creating large within-depot differences. These cytokines had minimal effects on lipolysis in perirenal or gonadal adipocytes. The authors conclude that adipocytes surrounding lymph nodes contribute little to whole-body energy supply during fasting, but are more sensitive than all others to cytokines and to noradrenalin, having higher maximum but lower minimum rates of lipolysis. These properties equip perinodal adipocytes for local interactions with lymphoid tissue.

Adipocytes↗

Vascularisation in adipose depots surrounding immune-stimulated lymph nodes.

We report a change in the vascularisation of the adipose depots surrounding the popliteal lymph node that has, and the contralateral node that has not, been exposed to a simulated immune challenge. The percentage of the depot that consists of vessels, as measured by image analysis, decreases over a period of 2 d after immune stimulus, then increases in a biphasic manner over the next 2-3 wk. By 1 mo after the stimulus, the vascularisation has returned to baseline values. The adipose tissue surrounding both the stimulated and the unstimulated lymph nodes shows a similar pattern, but the unstimulated depot lags by 3-6 d in reaching its maximum vascularisation. These data support the hypothesis that perinodal adipose tissue is involved in peripheral immune responses.

Adipose Tissue↗

In vivo evidence for the involvement of the adipose tissue surrounding lymph nodes in immune responses.

Spontaneous lipolysis in the adipocytes surrounding the popliteal lymph node rose within 1 h of its being activated with a subcutaneous injection of lipopolysaccharide (LPS), reached a peak after 6-9 h, then declined almost to basal levels after 24 h. The response of adipocytes from elsewhere in the same depot was delayed and smaller. Following the simulated immune challenge, perinodal adipocytes were consistently more sensitive to noradrenalin at 10(-8) and 10(-7) M than those elsewhere in the same depot, but the maximum lipolysis, in the presence of 10(-5) M noradrenalin, was similar in all popliteal samples. These effects were increased by incubating adipose tissue explants for 24 h in tissue culture medium, suggesting autocrine amplification of the initial stimuli. Incubation with interleukin-4 (IL-4, 10 ng/ml) abolished the increase in lipolysis in samples around the activated lymph node and depressed it to below control values in other adipocytes. In vivo stimulation of the popliteal node increased maximum lipolysis in the presence of 10(-5) M noradrenalin in samples from around mesenteric lymph nodes and after 24 h incubation, in omental perinodal adipocytes. No effects of any pre-treatments were detected in perirenal adipocytes. We conclude that the adipocytes surrounding lymph nodes are actively involved in local, transient immune responses. Their participation may explain why most major lymph nodes are embedded in adipose tissue.

Adipocytes↗

Immunofluorescent localisation of tumour necrosis factor-alpha receptors on the popliteal lymph node and the surrounding adipose tissue following a simulated immune challenge.

We used immunohistochemical techniques to demonstrate the distribution of receptors for the cytokine tumour necrosis factor-alpha on the popliteal lymph node and the adipose tissue surrounding it for 5 d following a simulated immune challenge to one hind leg in the rat. We found different patterns of expression of receptors on adipocytes surrounding a lymph node to a distance of about 1 mm, and on those more remote from the node. Sites recognised by an antibody to type I tumour necrosis factor receptors appeared on the challenged node and the adipocytes surrounding it within 30 min of an injection of bacterial lipopolysaccharide, but appeared on adipocytes surrounding the unchallenged popliteal node only 24 h later. Adipocytes distant from the node, both within the same depot and in the contralateral depot, showed no response. Sites recognised by an antibody to type II tumour necrosis factor receptors were present at all times on lymph nodes and the adipocytes close to them, but appeared on more distant adipocytes only 24 h after immune challenge, in both challenged and unchallenged legs. These data support the proposal, based on in vitro studies, that the adipose tissue surrounding major lymph nodes is specialised to respond to cytokines derived from lymphoid cells, and participates in the immune responses of the adjacent node.

Adipose Tissue↗

Adaptations of maternal adipose tissue to lactation.

The ability to store substantial amounts of energy as lipid in adipose tissue has allowed development of a variety of strategies in wild animals to meet the considerable metabolic challenge of lactation. The ability to use adipose tissue energy has also been critical for development of the exceptional rates of milk production achieved in the dairy cow. Lactation thus results in profound changes in adipose tissue metabolism, the molecular bases of which are beginning to be resolved in domestic ruminants and laboratory rodents. In addition to its role as an energy store, adipose tissue has a variety of other functions (e.g., modulation of mammary development, appetite, immune system function), some of which are important for lactation.

Adaptation, Physiological↗

The effects of feeding suet-enriched chow on site-specific differences in the composition of triacylglycerol fatty acids in adipose tissue and its interactions in vitro with lymphoid cells.

The effects of diet on the composition and properties of adipose tissue in relation to lymph nodes were studied in adult guinea-pigs. The proportions of monoenoic triacylglycerol fatty acids were constant in all sites in adipose tissue of similarly fed guinea-pigs, but were substantially greater in samples from guinea-pigs fed on suet-enriched chow. Triacylglycerols in adipose tissue from near nodes contained significantly fewer saturated fatty acids, and significantly more 18:2n-6 and 18:3n-3 than those in samples from sites remote from nodes within the same depot. Depots that interact most strongly with lymphoid cells in vitro had the largest and most consistent within-depot differences. The gradients of triacylglycerol fatty acid composition with distance from lymph nodes in two small intermuscular depots were similar in guinea-pigs fed on plain or suet-enriched chow. These findings are consistent with the hypothesis that adipose tissue around lymph nodes is specialized for local interactions with the lymphoid cells therein, and help to explain the variability of serial or duplicate measurements of adipose tissue composition. When cultured alone, lipopolysaccharide-stimulated lymph node lymphoid cells from suet-fed guinea-pigs incorporated as much labelled thymidine as the controls. Adipose tissue explants from suet-fed guinea-pigs inhibited lymphocyte proliferation much less than those of the controls, although the site-specific differences were similar. The pattern of site-specific differences in glycerol released from explants incubated alone was generally similar for both dietary groups, but except in the popliteal depot, the increases following co-culturing with lymphoid cells were smaller for samples from suet-fed guinea-pigs. These experiments show that minor changes in the fatty acid composition of the diet can substantially alter the interactions between adipose tissue and lymphoid cells.

Adipose Tissue↗

Interactions between adipose tissue around lymph nodes and lymphoid cells in vitro.

The functional relationships between lymphoid cells and the adipose tissue that surrounds lymph nodes were investigated in healthy adult guinea pigs. Lymphoid cells extracted from healthy adult guinea pigs were co-cultured for 48 h with adipose tissue explants from 18 sites defined by their anatomical relations to lymph nodes. Such explants from near a node suppressed lymphocyte proliferation stimulated with concanavalin A or lipopolysaccharide more than those from sites 5-10 mm from nodes. Inhibition was almost completely abolished by 500 microU insulin. The presence of lymphoid cells increased lipolysis (measured as glycerol release) in adipose tissue from all depots containing lymph nodes (i.e., except perirenal), especially in the presence of mitogens and with near-node samples from intermuscular and mesenteric depots. Inhibition of lymphocyte proliferation by adipose tissue was proportional to the additional lipolysis stimulated by the presence of lymphoid cells. For all depots except the mesenteric, glycerol release stimulated by lymphoid cells was inversely proportional to spontaneous lipolysis in adipose tissue cultured alone. These experiments demonstrate reciprocal interactions between lymphoid cells and adipose tissue, especially that around lymph nodes. The mediators of the action of adipose tissue on lymphoid cells probably include lipolytic products; mediators of the inverse effects are unknown.

Adipose Tissue↗

Site-specific properties of human adipose depots homologous to those of other mammals.

1. Mean adipocyte volume, collagen content and the maximum activities of hexokinase and phosphofructokinase were measure in 15 depots of 8 men who were in good health until their sudden death. The data were used to establish homologies between depots in humans and other mammals. 2. The basic organization of adipose tissue in humans is similar to that of other mammals, although additional depots that are minimal or absent in rodents may be massive in humans. 3. Known site-specific properties relevant to manipulation of adipose tissue are reviewed.

Abdominal Muscles↗