Adipose-immune interactions during obesity and caloric restriction:

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reciprocal mechanisms regulating immunity and health span
Vishwa Deep Dixit1 Laboratory of Neuroendocrine-Immunology, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA

Abstract: Increasing evidence suggests a tight coupling of metabolic and immune systems. This cross-talk mediated by neuroendocrine peptides as well as numerous cytokines andchemokines is believed to be responsible for integrating energy balance to immune function. These neuroendocrineimmune interactions are heightened during the state of chronic positive energy balance, as seen during obesity, and negative energy balance caused by caloric restriction (CR). Emerging evidence suggests that obesity may be associated with an immunodeficient state and chronic inflammation,which contribute to an increased risk of premature death. The direct interactions between expanded leukocyte populations within the adipose tissue during obesity and an increased number of adipocytes within an aging lymphoid microenvironment may constitute an important adaptive or pathological response as a result of change in energy balance. In stark contrast to obesity, CR causes negative energybalance and robustly prolongs a healthy lifespan in all of the species studied to date. Therefore, the endogenous neuroendocrine-metabolic sensors elevated or suppressed as a result of changes in energy balance may offer an important mechanism in understanding the antiaging and potential immune-enhancing nature of CR. Ghrelin, one such sensor of negative energy balance, is reduced during obesityand increased by CR. Ghrelin also regulates immune function by reducing proinflammatory cytokines and promotes thymopoiesis during aging and thus, may be a new CR mimetic target. The identification of immune effects and molecular pathways used by such orexigenic metabolic factors could offer potentially novel approaches to enhance immunity and increase healthy lifespan. J. Leukoc. Biol. 84: 882–892; 2008.

INTRODUCTION
Charles Darwin famously noted that “Evolution is how life commutes its own death sentence”. Arguably, the survival and evolution of the human race are intimately linked with the drive to find and accumulate food as well as the ability to sense and successfully clear pathogens. The discrepancy between the environment, in which hunger and the immune system evolved inprehistoric times, is vastly different from the calorie-rich “obesogenic” environment in the modern world. It has been hypothesized that because of the scarce availability of food throughout most of human evolution, dominant genetic pathways were shaped in favor of increasing caloric intake over the mechanisms causing reduction in energy intake [1]. An increase in the availability of high-calorie foodsand exposure of these dominant genetic traits [2] have led to an alarming increase in obesity. The rise in obesity-associated diseases has raised concerns that the steady increase in life expectancy during the past centuries may not be sustainable. Indeed, obesity has been shown to have a substantial negative effect on longevity, reducing the length of life of people who are severely obese by anestimated 5–20 years [3]. Data from the National Health and Nutrition Examination Survey suggest that close to 33% of the adult U.S. population is obese, and 17% of children and adolescents are overweight [4]. According to current predictions, the prevalence and severity of obesity and its complications will worsen [5]. Given the increasing trends of obesity in younger ages, a large group ofindividuals will carry and express the obesity-related risks for a longer period of their lifespan. How this growing number of the adult obese population will age immunologically may have significant health and societal implications. This overview provides insights into how immune function is affected by metabolic states of chronic caloric excess seen during obesity with an emphasis on interactions...
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