Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARα, PPARβ/δ, and PPARγ, have been identified so far. PPARα is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs (e.g., fenofibrate). PPARβ/δ is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPARα or PPARγ target genes. PPARγ1 and γ2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPARγ1 is expressed in colon, immune system (e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Ligand-dependent transactivation, ligand-independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPARα agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPARα agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPARγ activators. In all the studies, both the PPARγ activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPARα and PPARγ may be a target for gastric ulcer therapy. Finally, more studies are also needed to confirm the involvement of PPARs α and γ in gastric ulcer.

Food entrainment in mice leads to sex- and organ-specific responses in the digestive system and nutrient metabolism

“…However, this rhythmicity seemed chaotic, with an appearance only in DF males and females and SDF females on the post-shift day 7 and in NF and SNF males on the post-shift day 3. Some studies have suggested that Pparα could regulate Gast expression and/or translation, indicating that they might belong to the same regulatory pathway (40, 41). However, we observed no similarities between their diurnal patterns.…”

“…Although its function is essential for nutrient digestion, the rhythmicity was highly chaotic, appearing and disappearing under various feeding conditions. Some studies have suggested that Pparα could regulate Gast expression and/or translation, indicating that they might belong to the same regulatory pathway (Saha, 2015; Bakke et al, 2002). However, we observed no similarities between their expression patterns.…”

Honokiol, an inducer of sirtuin‐3, protects against non‐steroidal anti‐inflammatory drug‐induced gastric mucosal mitochondrial pathology, apoptosis and inflammatory tissue injury

“…It is worth mentioning that in addition to its direct Sirt3‐stimulating effect, honokiol is also credited with partial agonism or activation of non‐adipogenic PPARγ (Atanasov et al, 2013). Moreover, PPARγ activation has also been reported to offer gastroprotection and hasten ulcer healing in rodent models (Saha, 2015). Therefore, possible PPARγ agonism by honokiol may also contribute to or synergize its collective gastroprotective response.…”

An Overview of the Role of Peroxisome Proliferator-activated Receptors in Liver Diseases

“…In this regard, PPARα is a significant target for fibrate hypolipidemic drugs, implicated mainly in the catabolism of FAs and their oxidation in the heart, muscle, liver, kidney, small and large intestine. 18 It also causes glucose homeostasis and insulin resistance. PPARα agonists reduce renal blood pressure by interfering in the renin angiotensin system and provide renal vasodilatation by promoting the expression of endothelial nitric oxide synthase (commonly known as eNOS) in endothelium.…”