科研之友
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摘要
Objective: Weight-loss is a near societal obsession and many diet programs use significant calorie restriction including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the ILI arm of the neuroimmune system was down-regulated by a 24 h fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 h. Expression of the endogenous ILI antagonists, ILI receptor type 2 (ILI R2), and ILI receptor antagonist (ILI RA) was determined as were sickness behaviors before and after IL-1 beta administration. Results: Fasting markedly increased gene expression of ILI R2 (83-fold in adipose tissue, 9.5-fold in liver) and 1151 RA (68-fold in liver). Fasted mice were protected from 1L-1 beta-induced weight-loss, hypoglycemia, loss of locomotor, and social anxiety. These protections were coupled to a large positive interaction of fasting and 115113 on ILI R2 gene expression in adipose tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased 1151 RA and 1151 R2 protein 2.5- and 3.2-fold, respectively, in liver but also increased 1151 R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent ILI R2 or ILI RA gene expression. Administration of the FFA, palmitate, to mice increased liver 1151 R2 and 1151 RA gene expression by 14- and II-fold, respectively. Conclusion:These findings indicate that fasting augments expression of endogenous ILI antagonists inducing 1151 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.
- 出版日期2014-7-9
