PPARs: therapeutic targets for metabolic disease

Berger, Joel P.; Akiyama, Taro E.; Meinke, Peter T.

doi:10.1016/j.tips.2005.03.003

Cited by 638 publications

(502 citation statements)

References 86 publications

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“…Obesity, insulin resistance, and hypertension are resulted from these lipid disorders, which together are known as the metabolic syndrome [11]. PPARs are regarded as important targets for the treatment of metabolic syndrome [5,14].…”

Section: Introductionmentioning

confidence: 99%

“…PPARc has been implicated as the primary receptor modulating the insulin sensitizing activity of the TZDs (Thiazolidinediones) class of anti-diabetic drugs [22], and it is well known for its role in adipogenesis at the cellular level [9]. Therefore, substantial attempts are being made to develop new therapeutic agents for hyperlipidemia, insulin resistance, or atherosclerosis based on their activity toward PPARs [5]. For example, PPAR a/c dual agonists were developed as effective therapeutic agents for the treatment of insulin resistance and hypertriglyceridemia in the metabolic syndrome [5].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, substantial attempts are being made to develop new therapeutic agents for hyperlipidemia, insulin resistance, or atherosclerosis based on their activity toward PPARs [5]. For example, PPAR a/c dual agonists were developed as effective therapeutic agents for the treatment of insulin resistance and hypertriglyceridemia in the metabolic syndrome [5].…”

Section: Introductionmentioning

confidence: 99%

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Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARα in bitter gourd (Momordica charantia L.)

et al. 2006

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SummaryBitter gourd (Momordica charantia L.) is a common vegetable in Asia that has been used in traditional medicine for the treatment of Diabetes. PPARs are ligand-dependent transcription factors that belong to the steroid hormone nuclear receptor family and control lipid and glucose homeostasis in the body. We previously reported that the ethyl acetate (EA) extract of bitter gourd activated peroxisome proliferator receptors (PPARs) a and c. To identify the active compound that activated PPARa, wild bitter gourd EA extract was partitioned between n-hexane and 90% methanol/10% H 2 O, and the n-hexane soluble fraction was further separated by silica gel column chromatography and finally by preparative HPLC. A transactivation assay employing a clone of CHOK1 cells stably transfected with a (UAS) 4 -tk-alkaline phosphatase reporter and a chimeric receptor of GAL4-rPPARa LBD was used to track the active component. Based on Mass, NMR, and IR spectroscopy, 9cis, 11trans, 13trans-conjugated linolenic acid (9c, 11t, 13t-CLN) was identified as a PPARa activator in wild bitter gourd. The isolated 9c, 11t, 13t-CLN rich fraction also significantly induced acyl CoA oxidase (ACO) activity in a peroxisome proliferator-responsive murine hepatoma cell line, H4IIEC3, implying that 9c, 11t, 13t-CLN was able to act on a natural PPARa signaling pathway as well. The content of 9c, 11t, 13t-CLN was estimated to be about 7.1 g/kg of our dried wild bitter gourd sample. The concentration of 9c, 11t, 13t-CLN and activation activity in the hydrolyzed EA extract of the seeds was higher than that of the flesh. The potential health benefits of 9c, 11t, 13t-CLN through the PPARa regulated mechanism are worthy to be further characterized in in vivo studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARα in bitter gourd (Momordica charantia L.)

et al. 2006

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“…We also deciphered the molecular mechanism of action, showing that MEHP acts as a SPPARM, 52 studies of which remain an important target for pharmaceutical research on type 2 diabetes. 64,65 Assessment of metabolic effects upon in utero and perinatal exposure to phthalates…”

Section: Pparc and Phthalates: Stepping In With The Definition Of A Smentioning

confidence: 99%

Interference of pollutants with PPARs: endocrine disruption meets metabolism

2008

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The concept of endocrine disruption emerged over a decade ago with the observation that several natural or industrial compounds can interfere with estrogen and androgen signaling, and thereby affect both male and female reproductive functions. Since then, many endocrine-disrupting chemicals (EDCs) have been identified and the concept has been broadened to receptors regulating other aspects of endocrine pathways. In that context, interference of EDCs with receptors regulating metabolism has been proposed as a factor that could contribute to metabolic diseases such as obesity and diabetes. We review recent studies showing that several pollutants, including phthalates and organotins, interfere with PPAR (peroxisome proliferator-activated receptors) nuclear receptors and may thereby affect metabolic homeostasis. Particular emphasis is given on the mechanisms of action of these compounds. However, unlike what has been suspected, we provide evidence from mouse models suggesting that in utero exposure to the phthalate ester di-ethyl-hexyl-phthalate most likely does not predispose to obesity. Collectively, these studies define a subclass of EDCs that perturb metabolic signaling and that we propose to define as metabolic disruptors.

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“…49 Thiazolidinediones (TZDs) can directly reduce peripheral systemic insulin resistance, 50 via the mighty activation of PPARγ, inducing the fat redirection from visceral to subcutaneous depots. 51 Given adipocytes own the highest PPARγ levels, these cells are the primary target for the glucose-lowering actions of TZDs.…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor-B: Impact on physiology and pathology

Zhu

Gao

et al. 2017

Cell Adhesion & Migration

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Angiogenesis plays an important role in controlling tissue development and maintaining normal tissue function. Dysregulated angiogenesis is implicated in the pathogenesis of a variety of diseases, particularly diabetes, cancers, and neurodegenerative disorders. As the major regulator of angiogenesis, the vascular endothelial growth factor (VEGF) family is composed of a group of crucial members including VEGF-B. While the physiological roles of VEGF-B remain debatable, increasing evidence suggests that this protein is able to protect certain type of cells from apoptosis under pathological conditions. More importantly, recent studies reveal that VEGF-B is involved in lipid transport and energy metabolism, implicating this protein in obesity, diabetes and related metabolic complications. This article summarizes the current knowledge and understanding of VEGF-B in physiology and pathology, and shed light on the therapeutic potential of this crucial protein.

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PPARs: therapeutic targets for metabolic disease

Cited by 638 publications

References 86 publications

Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARα in bitter gourd (Momordica charantia L.)

Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPARα in bitter gourd (Momordica charantia L.)

Interference of pollutants with PPARs: endocrine disruption meets metabolism

Vascular endothelial growth factor-B: Impact on physiology and pathology

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