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Nathan Goodyear

PPARs, Obesity, and Inflammation - 0 views

  • increase of 61% within 10 years
  • Many of the inflammatory markers found in plasma of obese individuals appear to originate from adipose tissue
  • 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
  • the peroxisome proliferators- activated receptor (PPAR) family are involved in the regulation of inflammation and energy homestasis
  • natural agonists, including unsaturated fatty acids and eicosanoids
  • PPARα also regulates inflammatory processes, mainly by inhibiting inflammatory gene expression
  • 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
  • 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.
  • 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
  • PPARγ is considered the master regulator of adipogenesis
  • Unsaturated fatty acids and several eicosanoids serve as endogenous agonists of PPARγ
  • PPARγ2, which is adipose-tissue specific
  • 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
  • and (2) by preventing removal of corepressor complexes from gene promoter regions resulting in suppression of inflammatory gene transcription
  • diet-induced obesity is associated with increased inflammatory gene expression in adipose tissue via adipocyte hypertrophy and macrophage infiltration
  • PPARγ is able to reverse macrophage infiltration, and subsequently reduces inflammatory gene expression
  • 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
  • By interfering with NF-κB signaling pathways, PPARγ is known to decrease inflammation in activated macrophages
  • Recent data suggest that activation of PPARγ in fatty liver may protect against inflammation
  • PPARs may influence the inflammatory response either by direct transcriptional downregulation of proinflammatory genes
  • anti-inflammatory properties of PPARs in human obesity
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    PPARs play pivotal in obesity.  PPARs appear to reduce the inflammatory cascade associated with obesity.  Downregulation of PPARs are associated with increased inflammation.  Natural PPARs include unsaturated fats and eicosanoids.
Nathan Goodyear

Effects of Peroxisome Proliferator-Activated Receptor-α and -γ Agonists on 11... - 0 views

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    PPAR alpha and/or PPAR gamma does not down regulate 11Beta-HSD1.
Nathan Goodyear

Treatment of Obesity-Related Complications with Novel Classes of Naturally Occurring PP... - 0 views

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    natural PPAR agonists.  Maybe provide some of the anti-inflammatory improved lipid metabolism without the side effects found in their synthetic counterpart avandia
Nathan Goodyear

Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimu... - 0 views

  • PPARγ agonists were shown to inhibit the β-amyloid-stimulated expression of the cytokine genes interleukin-6 and tumor necrosis factor α. Furthermore, PPARγ agonists inhibited the expression of cyclooxygenase-2.
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    Not that we are recommending NSAIDS to reduce inflammation: but the learned biochemical pathways of inflammation involved with AD, allows a natural approach to reduce microglial associated inflammation through PPAR-gamma activation.
Nathan Goodyear

Adiponectin translation is increased by the PPARγ agonists pioglitazone and ω... - 0 views

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    Omeg-3, DHA and EPA, increased adiponectin production.  In addition, blockade of the PPAR-gamma resulted in a reduction in adiponectin production.  Thus PPAR gamma activation results in adiponectin production by adipocytes.
Nathan Goodyear

Inflammatory Mechanisms in Alzheimer's Disease: Inhibition of β-Amyloid-Stimu... - 0 views

  • The activated microglia mount a complex local proinflammatory response
  • PPARγ plays a critical role in regulating the inflammatory responses of microglia and monocytes to β-amyloid
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    microglial and inflammatory response in Alzheimer's disease.  Agonists of PPAR-gamma inhibit this action.  This has important implications in reducing the local inflammatory response found in the brains of those with Alzheimers and other neuordegenerative disease.
Nathan Goodyear

Natural product agonists of peroxisome proliferator-activated receptor gamma ... - 0 views

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    to read.
Nathan Goodyear

ingentaconnect Adipose Tissue Macrophages, Low Grade Inflammation and Insulin Re... - 0 views

  • “M1” or “classically activated” macrophages
  • PPAR-gamma agonists
  • “M2” or an “alternatively activated” anti-inflammatory phenotype
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    ATMs and obesity induced inflammation initiates insulin resistance and thus type II diabetes. The bodies reaction to a fat cell is no different than a bacterial, viral, or parasitic infection.  The body recognizes something (fat) that shouldn't be there and it attempts to destroy it and remove it.
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