Unraveling the Effects of PPARβ/δ on Insulin Resistance and Cardiovascular Disease

Vázquez‐Carrera, Manuel

doi:10.1016/j.tem.2016.02.008

Cited by 64 publications

(55 citation statements)

References 94 publications

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“…In recent years there has been a great interest in the actions of PPARα and PPARγ. PPARδ has roles in metabolism similar to PPARα and PPARγ such as improving glycemic control, decreasing insulin resistant and elevating high-density lipoprotein [49–51]. In addition, PPARδ was reported to have pro-angiogenic effects [5] unlike PPARα and PPARγ [52].…”

Section: Discussionmentioning

confidence: 99%

Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice

Zhao

Guo

et al. 2016

PLoS ONE

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Diabetic mellitus (DM) patients are at an increased risk of developing peripheral arterial disease (PAD). Danhong injection (DHI) is a Chinese patent medicine widely used for several cardiovascular indications but the mechanism of action is not well-understood. We investigated the therapeutic potential of DHI on experimental PAD in mice with chemically induced as well as genetic (KKAy) type 2 DM and the overlapping signaling pathways regulating both therapeutic angiogenesis and glucose homeostasis. Compared with normal genetic background wild type (WT) mice, both DM mice showed impaired perfusion recovery in hind-limb ischemia (HLI) model. DHI treatment significantly accelerated perfusion recovery, lowered blood glucose and improved glucose tolerance in both DM models. Bioluminescent imaging demonstrated a continuous ischemia-induced vascular endothelial growth factor receptor 2 (VEGFR-2) gene expressions with a peak time coincident with the maximal DHI stimulation. Flow cytometry analysis showed a DHI-mediated increase in endothelial progenitor cell (EPC) mobilization from bone marrow to circulating peripheral blood. DHI administration upregulated the expression of vascular endothelial growth factor A (VEGF-A) and VEGF receptor-2 (VEGFR-2) in ischemic muscle. A cross talk between ischemia-induced angiogenesis and glucose tolerance pathways was analyzed by Ingenuity Pathway Analysis (IPA) which suggested an interaction of VEGF-A/VEGFR-2 and peroxisome proliferator-activated receptor δ (PPARδ)/peroxisome proliferator-activated receptor γ (PPARγ) genes. We confirmed that upregulation of VEGF-A/VEGFR-2 by DHI promoted PPARδ gene expression in both type 2 diabetic mice. Our findings demonstrated that a multi-component Chinese medicine DHI effectively increased blood flow recovery after tissue ischemia in diabetic mice by promoting angiogenesis and improving glucose tolerance through a concomitant activation of VEGF-A/VEGFR-2 and PPARδ signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice

Zhao

Guo

et al. 2016

PLoS ONE

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“…PPARδ (also known as PPARβ) is ubiquitously expressed and when activated it promotes fatty acid oxidation, thermogenesis, insulin sensitivity, high density lipoprotein cholesterol (HDLc) levels in plasma and overall energy expenditure 7 . PPARδ deficient mice are prone to obesity and insulin resistance when challenged with a high-fat diet (HFD).…”

Section: Introductionmentioning

confidence: 99%

Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia

Doktorova

Zwarts

Zutphen

et al. 2017

Sci Rep

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Peroxisome proliferator-activated receptor δ (PPARδ) is a ligand-activated transcription factor that has an important role in lipid metabolism. Activation of PPARδ stimulates fatty acid oxidation in adipose tissue and skeletal muscle and improves dyslipidemia in mice and humans. PPARδ is highly expressed in the intestinal tract but its physiological function in this organ is not known. Using mice with an intestinal epithelial cell-specific deletion of PPARδ, we show that intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia. Furthermore, absence of intestinal PPARδ abolished the ability of PPARδ agonist GW501516 to increase plasma levels of HDL-cholesterol. Together, our findings show that intestinal PPARδ is important in maintaining metabolic homeostasis and suggest that intestinal-specific activation of PPARδ could be a therapeutic approach for treatment of the metabolic syndrome and dyslipidemia, while avoiding systemic toxicity.

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“…PPARβ/δ activation inhibits human macrophage foam cell formation and inflammation induced by VLDL and it also exerts favorable effects on HDL-C level [41]. Moreover, relevant study showed that PPARβ/δ agonist treatment decreased plasma TG, Apo-B, total and LDL-cholesterol [42].…”

Section: Discussionmentioning

confidence: 99%

Hypolipidemic effect of XH601 on hamsters of Hyperlipidemia and its potential mechanism

et al. 2017

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BackgroundThe novel compound XH601 is a synthesized derivative of formononetin. The present study was to investigate the hypolipidemia effect and potential mechanism of XH601.MethodsMale Golden Syrian hamsters were induced by high-fat diet (HFD) for eight weeks and the hyperlipidemic model was established successfully. After XH601 treatment, serum and hepatic biochemistry parameters of hamsters were detected and the effect of XH601 on adipose tissue was also analyzed. Furthermore, 3 T3-L1 cell differentiation by Oil-Red-O staining was observed and the mRNA and protein expression of peroxisome proliferator-activated receptors (PPARs) were measured by qRT-PCR and Western-blot in mature adipocytes.ResultsThe in vivo results suggest that XH601 significantly decreased the adipose weight and levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), apolipoprotein B (Apo-B), apolipoprotein E (Apo-E), while increased serum high-density lipoprotein (HDL-C). The in vitro results implied that XH601 up-regulated the mRNA and protein expression of both PPARα and PPARβ/δ in a dose-dependent manner.ConclusionsThe study suggests that XH601 exhibited strong ability to improve the dyslipidemia in hamsters fed with high-fat diet. The potential mechanism of XH601 was associated with the up-regulation of PPARα and PPARβ/δ mRNA and protein expression.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-017-0472-z) contains supplementary material, which is available to authorized users.

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Unraveling the Effects of PPARβ/δ on Insulin Resistance and Cardiovascular Disease

Cited by 64 publications

References 94 publications

Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice

Coordinated Activation of VEGF/VEGFR-2 and PPARδ Pathways by a Multi-Component Chinese Medicine DHI Accelerated Recovery from Peripheral Arterial Disease in Type 2 Diabetic Mice

Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia

Hypolipidemic effect of XH601 on hamsters of Hyperlipidemia and its potential mechanism

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