Characterization and biological roles of the peroxisome proliferator-activated receptor (PPAR) isotypes are well known in monogastrics, but not in ruminants. However, a wealth of information has accumulated in little more than a decade on ruminant PPARs including isotype tissue distribution, response to synthetic and natural agonists, gene targets, and factors affecting their expression. Functional characterization demonstrated that, as in monogastrics, the PPAR isotypes control expression of genes involved in lipid metabolism, anti-inflammatory response, development, and growth. Contrary to mouse, however, the PPAR gene network appears to controls milk fat synthesis in lactating ruminants. As in monogastrics, PPAR isotypes in ruminants are activated by long-chain fatty acids, therefore, making them ideal candidates for fine-tuning metabolism in this species via nutrients. In this regard, using information accumulated in ruminants and monogastrics, we propose a model of PPAR isotype-driven biological functions encompassing key tissues during the peripartal period in dairy cattle. 1. Introduction In humans, mouse, and rat, nuclear receptors (NR), including PPARs, form a transcription factor family of 47–49 members [1]. Activity of NR allows for long-term (hours to days) control of metabolism because they can affect mRNA expression of target genes, including metabolic enzymes [2]. Thus, NR represent an important regulatory system in cells, tissues, and organs playing a central role in metabolic coordination of the entire organism. Peroxisome proliferator-activated receptors (PPARs) were originally identified in Xenopus frogs [3] as novel members of the NR that induced the proliferation of peroxisomes in cells, a process that was accompanied by activation of the promoter of the acyl-CoA oxidase gene (ACOX1) encoding the key enzyme of peroxisomal long-chain fatty acid (LCFA) β-oxidation. The PPARα was the first member or isotype of the PPARs to be discovered in mammals during the search of a molecular target for liver peroxisome proliferators [4]. Those compounds include hypolipidemic drugs, that is, fibrates (e.g., clofibrate, fenofibrate, or Wy-14643), whose main effect is to lower blood triacylglycerol (TAG) and regulate cholesterol concentrations [5]. Initial characterization of PPARα (gene symbol PPARA in human and ruminants) in the adult mouse revealed that it was highly expressed in liver, kidney, and heart [4]. Shortly after PPARα was discovered, the isotypes PPARγ (gene symbol PPARG) and PPARβ/δ (gene symbol PPARD) were cloned [3, 6]. In
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