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We are analyzing https://www.nature.com/articles/nrendo.2016.135.

Title:
PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD | Nature Reviews Endocrinology
Description:
Peroxisome proliferator-activated receptors (PPARs) are integrators of both inflammatory and metabolic signalling networks. In this Review, the authors provide a comprehensive overview of how PPARs contribute to the development of metabolic disorders and how pharmacologically targeting these pathways can be used to develop new therapeutics for such diseases. Obesity is a worldwide epidemic that predisposes individuals to cardiometabolic complications, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which are all related to inappropriate ectopic lipid deposition. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are highly needed. The peroxisome proliferator-activated receptors (PPARs) modulate several biological processes that are perturbed in obesity, including inflammation, lipid and glucose metabolism and overall energy homeostasis. Here, we review how PPARs regulate the functions of adipose tissues, such as adipogenesis, lipid storage and adaptive thermogenesis, under healthy and pathological conditions. We also discuss the clinical use and mechanism of PPAR agonists in the treatment of obesity comorbidities such as dyslipidaemia, T2DM and NAFLD. First generation PPAR agonists, primarily those acting on PPARγ, are associated with adverse effects that outweigh their clinical benefits, which led to the discontinuation of their development. An improved understanding of the physiological roles of PPARs might, therefore, enable the development of safe, new PPAR agonists with improved therapeutic potential.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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  • Education
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Keywords {🔍}

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Topics {✒️}

peroxisome proliferator-activated receptor-β/-δ nature portfolio peroxisome proliferator-activated receptor-α peroxisome proliferator-activated receptor-δ permissions reprints privacy policy net/cymabay/media/9af11b3859e3b4fa04eff0f43424ffb5 peroxisome proliferator-activated receptor peroxisome proliferator-activated receptors advertising int/mediacentre/factsheets/fs311/en/ lipoatrophic a-zip/f-1 mice portal pressure fatty acid-induced dysfunction ppar-γ regulates osteoclastogenesis nature 444 nature 485 nature 466 nature 517 nature 502 nature diet-induced hepatic steatosis service pparβ/δ-mediated lipogenesis adipose subtype-selective recruitment author information authors adipocyte-derived th2 cytokines erk/cdk5 axis controls diet-induced obese mice obesity-induced hepatic steatosis amiloride-sensitive channel enac targeting ppar-α expression lipin 1–pgc1α–pparα pathway sirt1-dependent signaling pathway δ promotes reversal ppar-β/-δ palmitate-treated β-cells collecting duct-specific deletion author correspondence nuclear receptor atlas female c57bl/6j mice social media national library macrophage-specific conditional knockouts ppar pan-agonist obesity-linked adipocyte inflammation gov/ct2/show/nct02121717 gov/ct2/show/nct01042106 fatty acid oxidation effective therapeutic approaches

Questions {❓}

  • Adiponectin, driver or passenger on the road to insulin sensitivity?
  • Modulating peroxisome proliferator-activated receptors for therapeutic benefit?

Schema {🗺️}

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      description: Peroxisome proliferator-activated receptors (PPARs) are integrators of both inflammatory and metabolic signalling networks. In this Review, the authors provide a comprehensive overview of how PPARs contribute to the development of metabolic disorders and how pharmacologically targeting these pathways can be used to develop new therapeutics for such diseases. Obesity is a worldwide epidemic that predisposes individuals to cardiometabolic complications, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), which are all related to inappropriate ectopic lipid deposition. Identification of the pathogenic molecular mechanisms and effective therapeutic approaches are highly needed. The peroxisome proliferator-activated receptors (PPARs) modulate several biological processes that are perturbed in obesity, including inflammation, lipid and glucose metabolism and overall energy homeostasis. Here, we review how PPARs regulate the functions of adipose tissues, such as adipogenesis, lipid storage and adaptive thermogenesis, under healthy and pathological conditions. We also discuss the clinical use and mechanism of PPAR agonists in the treatment of obesity comorbidities such as dyslipidaemia, T2DM and NAFLD. First generation PPAR agonists, primarily those acting on PPARγ, are associated with adverse effects that outweigh their clinical benefits, which led to the discontinuation of their development. An improved understanding of the physiological roles of PPARs might, therefore, enable the development of safe, new PPAR agonists with improved therapeutic potential.
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