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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Regul+Integr+Comp+Physiol
2014 ; 307
(12
): R1458-70
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Dynamic and extensive metabolic state-dependent regulation of cytokine expression
and circulating levels
#MMPMID25320344
Petersen PS
; Lei X
; Seldin MM
; Rodriguez S
; Byerly MS
; Wolfe A
; Whitlock S
; Wong GW
Am J Physiol Regul Integr Comp Physiol
2014[Dec]; 307
(12
): R1458-70
PMID25320344
show ga
Cytokines play diverse and critical roles in innate and acquired immunity, and
several function within the central nervous system and in peripheral tissues to
modulate energy metabolism. The extent to which changes in energy balance impact
the expression and circulating levels of cytokines (many of which have
pleiotropic functions) has not been systematically examined. To investigate
metabolism-related changes in cytokine profiles, we used a multiplex approach to
assess changes in 71 circulating mouse cytokines in response to acute (fasting
and refeeding) and chronic (high-fat feeding) alterations in whole body
metabolism. Refeeding significantly decreased serum levels of IL-22, IL-1?,
soluble (s)IL-2R?, and soluble vascular endothelial growth factor receptor 3
(VEGFR3), but markedly increased granulocyte colony-stimulating factor (G-CSF),
IL-1?, chemokine (C-C motif) ligand (CCL2), sIL-1RI, lipocalin-2, pentraxin-3,
tissue inhibitor of metalloproteinase (TIMP-1), and serum amyloid protein (SAP)
relative to the fasted state. Interestingly, only a few of these changes
paralleled the alterations in expression of their corresponding mRNAs. Functional
studies demonstrated that central delivery of G-CSF increased, whereas IL-22
decreased, food intake. Changes in food intake were not accompanied by acute
alterations in orexigenic (Npy and Agrp) and anorexigenic (Pomc and Cart)
neuropeptide gene expression in the hypothalamus. In the context of chronic
high-fat feeding, circulating levels of chemokine (C-X-C) ligand (CXCL1), serum
amyloid protein A3 (SAA3), TIMP-1, ?1-acid glycoprotein (AGP), and A2M were
increased, whereas IL-12p40, CCL4, sCD30, soluble receptor for advanced glycation
end products (sRAGE), CCL12, CCL20, CX3CL1, IL-16, IL-22, and haptoglobin were
decreased relative to mice fed a control low-fat diet. These results demonstrate
that both short- and long-term changes in whole body metabolism extensively alter
cytokine expression and circulating levels, thus providing a foundation and
framework for further investigations to ascertain the metabolic roles for these
molecules in physiological and pathological states.
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