The transcriptional factors of peroxisome proliferator-activated receptors (PPARs) contain three different isoforms, namely nuclear receptor subfamily PPARα or NR1C1, PPARβ/δ or NR1C2, and PPARγ or NR1C3 [27,28,29]. These isoforms are expressed in multiple tissue and organs with identical character and ligand specificity [30]. The PPAR-α is expressed mainly in the liver but is also present in muscle, bone, and heart. The PPAR-δ is expressed in most parts of the body and regulates energy expenditure [31,32]. The PPAR-γ is expressed in vascular smooth muscle cells, and endothelial cells [33,34]. The expression of various types of PPARs is shown in Figure 3 [35,36,37].

In the human body, the three forms of PPARs are responsible for the activation of most of the enzymes that are required for fatty acid oxidation, glucose metabolism, and lipid metabolism [38]. These PPARs perform specific or distinct functions such as cellular energy balancing, and maintenance of energy homeostasis on their own or by helping each other [39]. Energy metabolism at a molecular level through PPARs is still not explained but when ligands are attached to these receptors, they transcript the genes involved in regulatory energy functions [40]. The PPARα is involved in the activation of gene-encoding enzymes such as carnitine palmityl transferase 1 (CPT1), fatty acid transport protein, acyl-CoA dehydrogenase or oxidase, or synthase required in the fatty acid oxidation pathway [41]. It also reduces plasma triglyceride levels and increases high-density lipoprotein, which gives benefits such as ketogenesis [42]. The PPARβ controls fatty acid metabolism, increases insulin sensitivity, obesity resistance, suppression of macrophage-derived inflammation, and also the formation of oxidative muscle fibers. The PPARγ promotes fatty acid uptake, and adipokine production raises insulin sensitivity, also in adipogenesis [43,44,45,46]. Other functions associated with PPARs are described in Figure 4 [47,48,49].

In several areas of medicinal chemistry, heterocyclic molecules are indispensable [50,51]. These compounds constitute nitrogen, sulfur, and oxygen atoms with various positional combinations in the cyclic ring [52]. Medicinal chemists and researchers always explore heterocycles due to their vital contribution to drug discovery and design by boosting the novel lead moieties with potential biological action in medicinal chemistry [53]. Based on statistics, more than 85% of biologically potential chemical moieties contain heterocyclic motifs [54]. Some of the most common heterocycles are pyrimidine, imidazole, oxazole, tetrazole, triazine, triazle, thiazole, indole, pyridine, thiophene, pyrazole, coumarin, oxindole, furan, etc. [55,56,57,58]. These heterocyclic nuclei possess a broad spectrum of medicinal potential such as an anti-microbial [59], antimalarial [60], anti-anxiety [61], anti-cancer [62], anti-depressant [63], anti-tubercular [64], anti-virus [65], anti-protozoal [66], and anti-convulsant, etc. Several heterocyclic analogs have been reported to affect PPAR in different diseases [67,68,69,70,71,72]. Apart from commercially available marketed drugs, Table 1. depicts the patented drugs acting on PPARs.