Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

The prevalence of obesity, a condition associated with increased health risks, has risen significantly over the past several decades. Although obesity develops from energy imbalance, its etiology involves a multitude of other factors. One of these factors are endocrine disruptors, or \"obesogens\", when in reference to obesity. Bisphenol A (BPA), a known endocrine disruptor used in plastic materials, has recently been described as an environmental obesogen. Although BPA-free products are becoming more common now than in the past, concerns still remain about the obesogenic properties of the compounds that replace it, namely Bisphenol S (BPS), Bisphenol F (BPF), and Bisphenol AF (BPAF). The purpose of this review is to investigate the relationship between BPA substitutes and obesity. Literature on the relationship between BPA substitutes and obesity was identified through PubMed and Google Scholar, utilizing the search terms \"BPA substitutes\", \"bisphenol analogues\", \"BPS\", \"BPF\", \"BPAF\", \"obesity\", \"obesogens\", \"adipogenesis\", \"PPARγ\", and \"adipocyte differentiation\". Various population-based studies were assessed to gain a better understanding of the epidemiology, which revealed evidence that BPA substitutes may act as obesogens at the pathophysiological level. Additional studies were assessed to explore the potential mechanisms by which these compounds act as obesogens. For BPS, these mechanisms include Peroxisome proliferator-activated receptor gamma (PPARγ) activation, potentiation of high-fat diet induced weight-gain, and stimulation of adipocyte hypertrophy and adipose depot composition. For BPF and BPAF, the evidence is more inconclusive. Given the current understanding of these compounds, there is sufficient concern about exposures. Thus, further research needs to be conducted on the relationship of BPA substitutes to obesity to inform on the potential public health measures that can be implemented to minimize exposures.

Atherosclerosis, a chief pathogenic factor of cardiovascular disease, is associated with many factors including inflammation, dyslipidemia, and oxidative stress. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and are widely expressed with tissue- and cell-specificity. They control multiple genes that are involved in lipid metabolism, inflammatory response, and redox homeostasis. Given the diverse biological functions of PPARs, they have been extensively studied since their discovery in 1990s. Although controversies exist, accumulating evidence have demonstrated that PPAR activation attenuates atherosclerosis. Recent advances are valuable for understanding the mechanisms of action of PPAR activation. This article reviews the recent findings, mainly from the year of 2018 to present, including endogenous molecules in regulation of PPARs, roles of PPARs in atherosclerosis by focusing on lipid metabolism, inflammation, and oxidative stress, and synthesized PPAR modulators. This article provides information valuable for researchers in the field of basic cardiovascular research, for pharmacologists that are interested in developing novel PPAR agonists and antagonists with lower side effects as well as for clinicians.

Phytochemicals have been used as one of the sources for the development of anti-obesity drugs. Plants are rich in a variety of bioactive compounds including polyphenols, saponins and terpenes. Phytochemicals inhibit adipocyte differentiation by inhibiting the transcription and translation of adipogenesis transcription factors such as C/EBPα and PPARγ. It has been proved that phytochemicals inhibit the genes and proteins associated with adipogenesis and lipid accumulation by activating Wnt/β-catenin signaling pathway. The activation of Wnt/β-catenin signaling pathway by phytochemicals is multi-target regulation, including the regulation of pathway critical factor β-catenin and its target gene, the downregulation of destruction complex, and the up-regulation of Wnt ligands, its cell surface receptor and Wnt antagonist. In this review, the literature on the anti-obesity effect of phytochemicals through Wnt/β-catenin signaling pathway is collected from Google Scholar, Scopus, PubMed, and Web of Science, and summarizes the regulation mechanism of phytochemicals in this pathway. As one of the alternative methods of weight loss drugs, Phytochemicals inhibit adipogenesis through Wnt/β-catenin signaling pathway. More progress in relevant fields may pose phytochemicals as the main source of anti-obesity treatment.

Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.

The search for new antiobesogenic agents is increasing because of the current obesity pandemic. Capsaicin (Caps), an exogenous agonist of the vanilloid receptor of transient potential type 1 (TRPV1), has shown promising results in the treatment of obesity. This scoping review aims to verify the pathways mediating the effects of Caps in obesity and the different methods adopted to identify these pathways. The search was carried out using data from the EMBASE, MEDLINE (PubMed), Web of Science, and SCOPUS databases. Studies considered eligible evaluated the mechanisms of action of Caps in obesity models or cell types involved in obesity. Nine studies were included and 100% (n = 6) of the in vivo studies showed a high risk of bias. Of the 9 studies, 66.6% (n = 6) administered Caps orally in the diet and 55.5% (n = 5) used a concentration of Caps of 0.01% in the diet. In vitro, the most tested concentration was 1 μM (88.9%; n = 8). Capsazepine was the antagonist chosen by 66.6% (n = 6) of the studies. Seven studies (77.8%) linked the antiobesogenic effects of Caps to TRPV1 activation and 3 (33.3%) indicated peroxisome proliferator-activated receptor (PPAR) involvement as an upstream connection to TRPV1, rather than a direct metabolic target of Caps. The main secondary effects of Caps were lower weight gain (33.3%; n = 3) or loss (22.2%; n = 2), greater improvement in lipid profile (33.3%; n = 3), lower white adipocyte adipogenesis (33.3%; n = 3), browning process activation (44.4%; n = 4), and higher brown adipocyte activity (33.3%; n = 3) compared with those of the control treatment. Some studies have shown that PPAR agonists modulate TRPV1 activity, and no study has evaluated the simultaneous antagonism of these 2 receptors. Consequently, further studies are necessary to elucidate the role of each of these signaling molecules in the antiobesogenic effects of Caps.

Autoimmune diseases are common diseases of the immune system that are characterized by the loss of self-tolerance and the production of autoantibodies; the breakdown of immune tolerance and the prolonged inflammatory reaction are undisputedly core steps in the initiation and maintenance of autoimmunity. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear hormone receptor family and act as ligand-activated transcription factors. There are three different isotypes of PPARs: PPARα, PPARγ, and PPARβ/δ. PPARγ is an established regulator of glucose homeostasis and lipid metabolism. Recent studies have demonstrated that PPARγ exhibits anti-inflammatory and anti-fibrotic effects in multiple disease models. PPARγ can also modulate the activation and polarization of macrophages, regulate the function of dendritic cells and mediate T cell survival, activation, and differentiation. In this review, we summarize the signaling pathways and biological functions of PPARγ and focus on how PPARγ and its agonists play protective roles in autoimmune diseases, including autoimmune thyroid diseases, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, primary Sjogren syndrome and primary biliary cirrhosis.

Thiazolidin-2,4-dione (TZD) possessing an active methylene constitute an important chemical class of compounds for the development of new drugs. So, many scholars have synthesized these derivatives as target molecules and evaluated their biological potential. Currently, some of the TZDs are synthesized to treat human cancers stating high levels of PPARγ because it is expected that activation of PPARγ arbitrates their anticancer activity because PPARγ ligands have recently been established to affect differentiation, cell proliferation and apoptosis of different cell types. In the present review, the synthesis of various derivatives of thiazolidine-2,4-diones, their mechanism of action and anticancer activity have been highlighted.

There is significant evidence of globally ubiquitous prenatal exposures to bisphenol A (BPA). Childhood obesity as an epidemic has been a global concern for over a decade. Experimental models and epidemiological evidence suggest that BPA may act as an obesogen during adipogenesis. Results from stem cell models and birth cohort studies support the developmental origins of health and disease theory. While literature reviews have presented a variety of potential mechanisms of BPA action during adipogenesis, there remains no consensus. This review is the first to explore the proliferator-activated receptor gamma (PPARγ) mechanism in detail. This review will also examine the obesogenic effect of prenatal exposure to BPA during critical windows of vulnerability. Although vast experimental literature exists, there is limited epidemiological evidence to support the hypothesis for the obesogenic effect of BPA. The primary goal of this review is to provide researchers with a roadmap of existing research and suggestions for future directions for analyzing the relationship between prenatal BPA exposures and childhood obesity.

Our study demonstrates that (C-X-C motif) ligand 9 and 11 (CXCL9, CXCL11) chemokines were absent basally in non-neoplastic thyroid (TFC) and papillary thyroid carcinoma (PTC) cells. Interferon (IFN)γ induced the chemokine secretion in TFC and PTC, while tumor necrosis factor (TNF)α induced it only in PTC. IFNγ+TNFα induced a synergistic chemokines release in PTC, and at a lower level in TFC. Peroxisome proliferator-activated receptor (PPAR)γ agonists suppressed dose-dependently IFNγ+TNFα-induced chemokine release in TFC, while stimulated it in PTC. PPARγ knocking down, by RNA interference technique in PTC cells, abolished the effect of PPARγ agonists on chemokines release. In PTC cells, PPARγ agonists reduced proliferation, and CXCL9 or CXCL11 (100 and 500 pg/mL) reduced proliferation and migration (P < 0.01, for all). In conclusion, in PTC cells: (a) IFNγ+TNFα induced a marked release of CXCL9 and CXCL11; (b) PPARγ agonists stimulated CXCL9 and CXCL11 secretion, while inhibited proliferation; (c) CXCL9 and CXCL11 inhibited proliferation and migration. The use of CXCL9 or CXCL11 as antineoplastic agents in PTC remains to be explored. HIGHLIGHTS: • IFNγ and IFNγ+TNFα induce dose-dependently CXCL9 (and less CXCL11) in PTC cells. • Rosi and Pio dose-dependently inhibit the PTC cells proliferation. • Rosi and Pio (at variance of normal TFC) stimulate CXCL9 or CXCL11 secretion. • CXCL9 or CXCL11 induce a significant antiproliferative effect in PTC cells. • Chemokines induced by IFNγ (CXCL9 or CXCL11) inhibit migration in PTC cells.