Interactions of Adipose and Lymphoid Tissues
3. CONCLUSIONS
direct competition for fuels and other resources. Fever and systemic immune responses combined with anorexia cause small mammals (including human infants) to lose weight and are thus regarded as deleterious. However, when adult mice were experimentally infected with Listeria and fed forcibly or ad libitum over the following days, weight loss (because of the combination of anorexia and high energy expenditure) correlated posi- tively with survival (177). Overriding anorexia by force-feeding seems to accelerate the progress of pathogens, and hasten death, the opposite of what would be expected if depletion of lipid and protein reserves suppressed immune function.
Dhurandhar, Vangipuram, and colleagues have championed the view that obesity can be promoted by long-term viral infection (92,178). Various viruses in domestic poultry, certain rodents, and monkeys have been implicated, but it is too early to speculate on the mechanism by which the metabolic changes associated with viral infection lead to obesity.
2.3.1. STARVATION ANDCACHEXIA
Famines, wars, and other tragedies have many times demonstrated in humans the association between undernutrition and increased susceptibility to pathogens and para- sites, especially those that invade through the gut and skin, presumably as a result of immune inadequacies (179). However, there are some paradoxes. Many animals man- age to remain healthy and breed normally while very lean, and “stress” rather than weight loss per se seems more important for impaired immune function in wild animals.
Although maintaining the immune system is energetically expensive (180), many wild animals manage to remain healthy and breed normally while very lean, as well as while very obese (90). Studies of human athletes (181) suggest that endocrine and paracrine changes caused by “stress,” rather than weight loss per se, impair immune function.
Under some circumstances, notably prolonged anorexia nervosa, immune function remains surprisingly efficient in spite of massive reduction in adipose tissue mass (182), less fever in response to infection (183), and altered plasma cytokines (184).
A notable feature of naturally lean mammals is the retention of a small amount of perinodal adipose tissue around major lymph nodes. Prolonged fasting in laboratory rodents does not raise lipolysis in perinodal adipocytes as much as in adipocytes not anatomically associated with lymphoid tissue (41). As long as local interactions between adipose and lymphoid tissues are unimpaired, the immune system can probably function over a wide range of body compositions. Obvious cachexia with extensive depletion of muscle protein seems to set in at about the same time as this perinodal adipose tissue dis- appears. Thus it is possible that deficiencies in perinodal adipose tissue and its capacity to support immune function, rather than reduction in whole body energy supplies per se, are the mechanism by which nutritional “stress” impairs immune function.
Trypanosoma cruzi, the protoctistan parasite that causes Chagas’ disease, can invade preadipocytes in vitro and alter their pattern of secretions (185). Similar behavior in vivo could explain the long-term changes in metabolism and body composition associ- ated with this disease.
lymphoid structures. As well as secreting and responding to cytokines, adipocytes asso- ciated with lymphoid structures selectively accumulate and store certain fatty acids, especially those that are essential precursors for eicosanoids and docosanoids, and release them in response to local lipolytic signals. Quality as well as quantity of fatty acids is important for efficient immune function. Local provisioning of lymphoid tissues partially emancipates immune function from changes in quantity and composition of food. Paracrine control of lipolysis by lymphoid cells reduces competition with other tissues for energy stores, thus enabling fever and other energetically expensive defenses against pathogens to take place simultaneously with immune responses and unrelated functions such as lactation and exercise. The partitioning of white adipose tissue into a few large and numerous small depots, many associated with lymphoid structures and other tissues (such as muscle), and its local, paracrine control evolved alongside the more elaborate and expensive immune system (38).
ACKNOWLEDGMENTS
I thank Dr. R. H. Colby for helpful comments on the manuscript, and the Leverhulme Trust, Bristol-Myers Squibb (USA), the Open University Trustees’ Fund, and the North West London Hospital Trust (St. Mark’s Hospital, Northwick Park) for financial support.
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