Modulation of PPAR-γby Nutraceutics as Complementary Treatment for Obesity-Related Disorders and Inflammatory Diseases

Abstract

A direct correlation between adequate nutrition and health is a universally accepted truth. The Western lifestyle, with a high intake of simple sugars, saturated fat, and physical inactivity, promotes pathologic conditions. The main adverse consequences range from cardiovascular disease, type 2 diabetes, and metabolic syndrome to several cancers. Dietary components influence tissue homeostasis in multiple ways and many different functional foods have been associated with various health benefits when consumed. Natural products are an important and promising source for drug discovery. Many anti-inflammatory natural products activate peroxisome proliferator-activated receptors (PPAR); therefore, compounds that activate or modulate PPAR-gamma (PPAR-γ) may help to fight all of these pathological conditions. Consequently, the discovery and optimization of novel PPAR-γ agonists and modulators that would display reduced side effects is of great interest. In this paper, we present some of the main naturally derived products studied that exert an influence on metabolism through the activation or modulation of PPAR-γ, and we also present PPAR-γ-related diseases that can be complementarily treated with nutraceutics from functional foods.

Rice bran prevents high-fat diet-induced inflammation and macrophage content in adipose tissue

“…Also, analysis of adipose tissue biomarkers associated with macrophage polarization in insulin resistance (i.e., Emr1, Itgax/MRC1 ratio, adiponectin and PPARγ) [40,41] revealed a significant restoration in the expression levels of these markers after 1 % RBEE administration. In agreement with this, oryzanol, one of the major components in rice bran, upregulated PPARγ expression in adipocytes [42][43][44][45]. Altogether, our data suggest that RBEE administration could change macrophage polarization in obesity.…”

Effect of feed supplementation with live yeast on the intestinal transcriptome profile of weaning pigs orally challenged with Escherichia coli F4

“…Conversely, a cluster of upregulated gene sets related to antioxidant activity matched with the antibiotic treatment, including particularly IGF-1, a key gene capable of reducing the induction of cell apoptosis while maintaining cell growth under oxidative stress (Baregamian et al, 2006), and THOC5 which reduces bacteria translocation and is a major regulator of homeostatic self-renewal within the intestinal crypt (Saran et al, 2013). Moreover, the CM diet was able to reduce the ETEC effect, increasing the expression of PPAR-γ, a gene widely recognized for its anti-inflammatory effect (Ortuño Sahagún et al, 2012) and confirming in vitro data (Zanello et al, 2011). On the other hand, the competitive administration of yeast did not completely protect the intestinal mucosa from the activation of several genes involved in mucosal inflammation.…”

Probing the intermolecular interactions of PPARγ-LBD with polyunsaturated fatty acids and their anti-inflammatory metabolites to infer most potential binding moieties

“…In the present study, we performed molecular docking of PPARγ against various PUFAs and its metabolites (henceforth called as bioactive lipids) [43], keeping co-crystal bound Rosiglitazone (BRL) as a reference structure (PDB ID: 4OF8). Further, the bound complexes were subjected to molecular dynamics simulation to compare the binding efficacies and to infer the agonistic binding modes of fatty acids, which are potential therapeutic molecules [44, 45], towards identification of the most potent and efficient bioactive lipid agonist targeting PPARγ (Fig. 1).…”