Caroline M. Pond

Adipose tissue in the mammalian heart and pericardium: Structure, foetal development and biochemical properties

1. The occurrence and relative abundance of adipose tissue around the heart and in the pericardium of wild and domesticated mammals are reviewed and some new data reported. 2. For macaque monkeys and a wide range of other adult mammals, the mean volume of epicardial adipocytes is constant at about half the average of that of other depots, although the relative mass of this depot is unrelated to the abundance of adipose tissue in the rest of the body. 3. In young adult guinea-pigs, the maximum rate of fatty acid synthesis is significantly higher in epicardial adipose tissue than that in the pericardial, perirenal and popliteal depots. 4. The rate of fatty acid release by epicardial adipose tissue is approximately twice that of the pericardial and perirenal depots. 5. The protein contents of guinea-pig epicardial and pericardial adipose tissue are similar, and are significantly higher than those of the perirenal and popliteal adipose tissue and there are no site-specific differences in the abundance of mitochondria. 6. In adult Macaca monkeys, the capacity of the epicardial adipose tissue for glucose utilization is about half that of the intra-abdominal depots. 7. The principal difference between epicardial adipose tissue and that elsewhere in the body is its greater capacity for fatty acid release. 8. It is suggested that cardiac adipose tissue may act as a local energy supply for adjacent myocardium and/or as a buffer against toxic levels of free fatty acids.

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.

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.

What are subcutaneous adipocytes really good for...

Abstract:  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.

Paracrine relationships between adipose and lymphoid tissues: implications for the mechanism of HIV-associated adipose redistribution syndrome.

The adipocytes anatomically associated with lymph nodes and omental milky spots have site-specific properties that equip them to interact locally with lymphoid cells. Paracine provisioning of peripheral immune responses improves their efficiency and emancipates activated lymphocytes from competition with other tissues for blood-borne nutrients. Prolonged disruption to such paracine interactions might contribute to the HIV-associated adipose redistribution syndrome, causing selective hypertrophy of the mesentery, omentum and other lymphoid tissue-containing adipose depots, while nodeless depots atrophy.

The Anatomy of Adipose Tissue in Captive Macaca Monkeys and Its Implications for Human Biology

In a sample of 31 sedentary, ad libitum-fed monkeys, most specimens had less than 5% adipose tissue by weight. Total fatness correlated closely with the number of adipocytes per kilogram lean body mass, but not at all with mean adipocyte volume, except in specimens below 5% fat. The total number of adipocytes per kilogram of lean body mass increased more than tenfold in the most obese specimens. These data suggest that, like humans but in contrast to laboratory rodents, adipocyte proliferation, not adipocyte enlargement, is the chief mechanism of adipose tissue expansion except in very lean monkeys. Adipose tissue was found in all the typical mammalian depots and in the superficial abdominal paunch, which enlarged disproportionately in obese specimens, forming an almost continuous layer over most of the body. Site-specific differences in the activities of some glycolytic enzymes were similar to those of other mammals. Adipocytes in the paunch depot showed biochemical properties in common with those in the groin depots. The distribution and cellularity of adipose tissue in normal humans were similar to those of exceptionally obese monkeys. Many of the interspecific and sex differences can be attributed to the much greater abundance of adipose tissue in humans, and may not be associated with hair reduction or aquatic habits. Some minor changes in the size or shape of certain adipose depots may have arisen recently under sexual selection. The relevance of laboratory rodents as animal models of human obesity is assessed from comparison of the cellular structure, anatomical distribution and enzyme profiles of adipose tissue in monkeys with those of human and other mammals.

Body mass and natural diet as determinants of the number and volume of adipocytes in eutherian mammals

Total dissection of a randomly collected sample of 202 adult and subadult eutherian mammals, combined with site‐specific adipocyte volume determination, shows that the number of adipocytes in the body is proportional to (Body Mass)0.74 for predominantly carnivorous species and to (Body Mass)0.78 for mainly herbivorous, nonruminant mammals. Adipocyte expansion or shrinkage, not proliferation or depletion of adipocyte number, is the principal mechanism of adipose tissue enlargement and reduction. Therefore, the adipocytes of large mammals are larger than those of smaller specimens of similar dietary habits and fatness. We suggest that the presence of more numerous, smaller adipocytes in smaller mammals is related to their higher mass‐specific metabolic rate. The adipose tissue of mammals with a predominantly carnivorous diet contains 4.6 times as many adipocytes as that of herbivorous nonruminants of similar body mass; but nonruminant herbivores are not necessarily fatter because the adipocytes of carnivorous mammals are proportionately smaller than those of nonruminant herbivores. We suggest that a carbohydrate‐based energy metabolism is associated with fewer, relatively larger adipocytes and that when lipids and proteins form the major dietary energy source, adipose tissue consists of a greater number of smaller adipocytes.

Different “Weight” of Cardiac and General Adiposity in Predicting Left Ventricle Morphology

Excess adiposity has been widely related to cardiac morphological changes. Nevertheless, the mechanistic link between increased adiposity and left ventricular (LV) morphology is controversial and not completely understood. In this context, several authors have recently debated the different “weight” of BMI as an index of general adiposity vs. the importance of the epicardial fat depot as a marker of local visceral adiposity in obesity‐related LV changes. Studies in uncomplicated obesity suggest that the role of BMI in predicting LV abnormalities remains rather doubtful. In contrast, several lines of evidence suggest that cardiac adiposity could play an important part in the development of cardiac modifications. Epicardial fat as an index of cardiac adiposity could have a functional and mechanical role in obesity‐related LV abnormalities. Epicardial fat is clinically correlated with LV mass, atrial dimensions, and diastolic function, but a causal effect of epicardial adipose tissue on cardiac chamber modifications remains to be demonstrated. Nevertheless, the close anatomical and functional relationship of epicardial adipose tissue to the adjacent myocardium should readily allow local, paracrine interactions between these tissues.

The source of fatty acids incorporated into proliferating lymphoid cells in immune-stimulated lymph nodes

To explore the hypothesis that proliferating lymphoid cells in immune-stimulated lymph nodes obtain nutrients locally from adjacent adipose tissue, adult guinea pigs were fed for 6 weeks on standard chow or on chow supplemented with 100 g suet, sunflower oil or fish oil/kg. All the guinea pigs ate standard chow for the last 5 d, during which swelling of one popliteal lymph node was stimulated by repeated local injection of lipopolysaccharide. The fatty acid compositions of phospholipids in both popliteal and in several mesenteric lymph nodes, and of triacylglycerols in eleven samples of adipose tissue defined by their anatomical relations to lymph nodes, were determined by GC. The proportions of fatty acids in the phospholipids extracted from the stimulated popliteal node correlated best with those of triacylglycerols in the surrounding adipocytes, less strongly with those of adipocytes elsewhere in depots associated with lymphoid tissue, but not with those of nodeless depots. The composition of triacylglycerols in the perinodal adipose tissue changed under local immune stimulation. We conclude that proliferating lymphoid cells in activated lymph nodes obtain fatty acids mainly from the triacylglycerols in adjacent perinodal adipose tissue. Immune stimulation prompts changes in the fatty acid composition of the triacylglycerols of adipocytes in node-containing depots that equip the adipose tissue for provisioning immune responses. Such local interactions show that specialised adipocytes can act as an interface between whole-body and cellular nutrition, and may explain why mammalian adipose tissue is partitioned into a few large and many small depots.

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 Crohns 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 Crohns 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 Crohns disease that could form the basis for further investigations.