Structural Diversity of Peroxisome Proliferators and Their Effects on Mammalian Liver Cells <i>in Vivo</i>

Iglesia, Felix A. de la; McGuire, Edward J.; Haskins, Jeffrey R.; Lalwani, Narendra D.

doi:10.1111/j.1749-6632.1996.tb18625.x

Cited by 9 publications

(2 citation statements)

References 25 publications

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“…We found that BEZ, like other fibrates, can induce hepatomegaly in mice (data not shown), which is consistent with previous studies (40), and may be attributable to its capacity to induce peroxisome proliferation (41). Peroxisomal proliferation is species specific (42,43) because fibrate treatment does not cause hepatomegaly and peroxisomal proliferation in primates and humans (44)(45)(46). The 0.5% BEZ dose used in our study was chosen according to three previous, independent mouse studies (9,20,39).…”

Section: Discussionsupporting

confidence: 88%

Bezafibrate Improves Insulin Sensitivity and Metabolic Flexibility in STZ-Induced Diabetic Mice

et al. 2016

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Bezafibrate (BEZ), a pan activator of peroxisome proliferator-activated receptors (PPARs), has been generally used to treat hyperlipidemia for decades. Clinical trials with type 2 diabetes patients indicated that BEZ also has beneficial effects on glucose metabolism, although the underlying mechanisms of these effects remain elusive. Even less is known about a potential role for BEZ in treating type 1 diabetes. Here we show that BEZ markedly improves hyperglycemia and glucose and insulin tolerance in mice with streptozotocin (STZ)-induced diabetes, an insulin-deficient mouse model of type 1 diabetes. BEZ treatment of STZ mice significantly suppressed the hepatic expression of genes that are annotated in inflammatory processes, whereas the expression of PPAR and insulin target gene transcripts was increased. Furthermore, BEZ-treated mice also exhibited improved metabolic flexibility as well as an enhanced mitochondrial mass and function in the liver. Finally, we show that the number of pancreatic islets and the area of insulin-positive cells tended to be higher in BEZ-treated mice. Our data suggest that BEZ may improve impaired glucose metabolism by augmenting hepatic mitochondrial performance, suppressing hepatic inflammatory pathways, and improving insulin sensitivity and metabolic flexibility. Thus, BEZ treatment might also be useful for patients with impaired glucose tolerance or diabetes.

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Section: Discussionsupporting

confidence: 88%

Bezafibrate Improves Insulin Sensitivity and Metabolic Flexibility in STZ-Induced Diabetic Mice

et al. 2016

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“…These agents are collectively named "peroxisome proliferators" (reviewed in Ref. [2]). The increase in the number of peroxisome was found to be associated with an induction of gene expression involved in fatty acid oxidation; thereby a receptor-mediated mechanism of action was postulated.…”

Section: Peroxisomementioning

confidence: 99%

PPAR and immune system—what do we know?

Zhang

Young

2002

International Immunopharmacology

101

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Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear steroid receptor superfamily. Originally, the receptors were identified as critical controllers for several key enzymes that catalyze the oxidation of fatty acids. PPARs consist of three members: PPAR-alpha, PPAR-beta/delta, and PPAR-gamma. Among them, PPAR-gamma is essential for controlling thermogenesis and adipocyte differentiation. The ligands for PPAR-gamma include 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2)--a metabolite from the prostaglandin synthesis pathway, and "glitazones"--drugs utilized in the treatment of patients with diabetes. The precursors for prostaglandins are fatty acids consumed from diet and these precursors have long been postulated to have a regulatory role in immune functions. Emerging evidence indicates that PPAR-gamma and its ligands are indeed important for the modulation of immune and inflammatory reactions. In this review, we will spotlight the molecular mechanisms of receptor/ligand function and how they may regulate immune and inflammatory reactions. We also propose that PPAR-gamma and its endogenous ligands are participating factors for Type 1/Type 2 T and NK cell differentiation and development. Deciphering the mechanism of action of PPAR-gamma and its ligands may lead to a new therapeutic regiment for treatment of diseases involving dysfunction of the immune system.

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