PPARs, Obesity, and Inflammation - 0 views
www.ncbi.nlm.nih.gov/...PMC1783744
obesity inflammation PPARs perioxisome proliferator-activated receptor
shared by Nathan Goodyear on 16 Jan 12
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increase of 61% within 10 years
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Many of the inflammatory markers found in plasma of obese individuals appear to originate from adipose tissue
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obesity is a state of chronic low-grade inflammation that is initiated by morphological changes in the adipose tissue.
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secretion of MCP-1, resistin, and other proinflammatory cytokines is increased by obesity, the adipose secretion of the anti-inflammatory protein adiponectin is decreased
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the peroxisome proliferators- activated receptor (PPAR) family are involved in the regulation of inflammation and energy homestasis
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upregulation of COX-2 is seen in alcoholic steatohepatitis and nonalcoholic steatohepatitis and has been directly linked to the progression of steatosis to steatohepatitis, the inhibitory effect of PPARα on COX-2 may reduce steatohepatitis
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PPARα agonists have a clear anorexic effect resulting in decreased food intake, evidence is accumulating that PPARα may also directly influence adipose tissue function, including its inflammatory status.
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PPARα may govern adipose tissue inflammation in three different ways: (1) by decreasing adipocyte hypertrophy, which is known to be connected with a higher inflammatory status of the tissue [3, 11, 59], (2) by direct regulation of inflammatory gene expression via locally expressed PPARα, or (3) by systemic events likely originating from liver
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two different molecular mechanisms have been proposed by which anti-inflammatory actions of PPARγ are effectuated: (1) via interference with proinflammatory transcription factors including STAT, NF-κB, and AP-1
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and (2) by preventing removal of corepressor complexes from gene promoter regions resulting in suppression of inflammatory gene transcription
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diet-induced obesity is associated with increased inflammatory gene expression in adipose tissue via adipocyte hypertrophy and macrophage infiltration
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PPARγ is able to reverse macrophage infiltration, and subsequently reduces inflammatory gene expression
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Inflammatory adipokines mainly originate from macrophages which are part of the stromal vascular fraction of adipose tissue [18, 19], and accordingly, the downregulation of inflammatory adipokines in WAT by PPARγ probably occurs via effects on macrophages
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By interfering with NF-κB signaling pathways, PPARγ is known to decrease inflammation in activated macrophages
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PPARs may influence the inflammatory response either by direct transcriptional downregulation of proinflammatory genes