Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
free free
Warning: file_get_contents(http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=18854155&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 445
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity Zhang X; Zhang G; Zhang H; Karin M; Bai H; Cai DCell 2008[Oct]; 135 (1): 61-73Overnutrition is associated with chronic inflammation in metabolic tissues. Whether metabolic inflammation compromises the neural regulatory systems and therefore promotes overnutrition-associated diseases remains unexplored. Here we show that a mediator of metabolic inflammation, IKKbeta/NF-kappaB, normally remains inactive although enriched in hypothalamic neurons. Overnutrition atypically activates hypothalamic IKKbeta/NF-kappaB at least in part through elevated endoplasmic reticulum stress in the hypothalamus. While forced activation of hypothalamic IKKbeta/NF-kappaB interrupts central insulin/leptin signaling and actions, site- or cell-specific suppression of IKKbeta either broadly across the brain or locally within the mediobasal hypothalamus, or specifically in hypothalamic AGRP neurons significantly protects against obesity and glucose intolerance. The molecular mechanisms involved include regulation by IKKbeta/NF-kappaB of SOCS3, a core inhibitor of insulin and leptin signaling. Our results show that the hypothalamic IKKbeta/NF-kappaB program is a general neural mechanism for energy imbalance underlying obesity and suggest that suppressing hypothalamic IKKbeta/NF-kappaB may represent a strategy to combat obesity and related diseases.|*Energy Metabolism[MESH]|*Signal Transduction[MESH]|Agouti-Related Protein/genetics/metabolism[MESH]|Animals[MESH]|Endoplasmic Reticulum/metabolism[MESH]|Humans[MESH]|Hypothalamus/immunology/*physiopathology[MESH]|I-kappa B Proteins/*metabolism[MESH]|Immunity, Innate[MESH]|Insulin Resistance[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|NF-kappa B/*metabolism[MESH]|Neurons/metabolism[MESH]|Obesity/metabolism[MESH]|Overnutrition/*physiopathology[MESH]|Suppressor of Cytokine Signaling 3 Protein[MESH]|Suppressor of Cytokine Signaling Proteins/metabolism[MESH] |