biology

Peroxisome proliferator-activated receptor delta

Peroxisome proliferator-activated receptor delta is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Peroxisome proliferator-activated receptor delta rather than just read about it. In short: Peroxisome proliferator-activated receptor delta (PPAR-delta), or (PPAR-beta), also known as Nuclear hormone receptor 1 (NUC1) is a nuclear receptor that in humans is encoded by the PPARD gene. This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family.

Key takeaways

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Reference excerpt

Peroxisome proliferator-activated receptor delta (PPAR-delta), or (PPAR-beta), also known as Nuclear hormone receptor 1 (NUC1) is a nuclear receptor that in humans is encoded by the PPARD gene. This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) family. It was first identified in Xenopus in 1993.

Function PPAR-delta is a nuclear hormone receptor that governs a variety of biological processes and may be involved in the development of several chronic diseases, including diabetes, obesity, atherosclerosis, and cancer. In muscle PPARD expression is increased by exercise, resulting in increased oxidative (fat-burning) capacity and an increase in type I fibers. Both PPAR-delta and AMPK agonists are regarded as exercise mimetics. In adipose tissue PPAR-β/δ increases both oxidation as well as uncoupling of oxidative phosphorylation. PPAR-delta may function as an integrator of transcription repression and nuclear receptor signaling. It activates transcription of a variety of target genes by binding to specific DNA elements. Well described target genes of PPARδ include PDK4, ANGPTL4, PLIN2, and CD36. The expression of this gene is found to be elevated in colorectal cancer cells. The elevated expression can be repressed by adenomatosis polyposis coli (APC), a tumor suppressor protein involved in the APC/beta-catenin signaling pathway. Knockout studies in mice suggested the role of this protein in myelination of the corpus callosum, epidermal cell proliferation, and glucose and lipid metabolism. This protein has been shown to be involved in differentiation, lipid accumulation, directional sensing, polarization, and migration in keratinocytes.

Role in cancer Studies into the role of PPAR-delta in cancer have produced contradictory results. Although there is some controversy, the majority of studies have suggested that PPAR-delta activation could result in changes that are favorable to cancer progression. Work by Wagner and colleagues has reported that vascular PPARβ/δ promotes tumour angiogenesis and progression.

Tissue distribution PPAR-delta is highly expressed in many tissues, including colon, small intestine, liver and keratinocytes, as well as in heart, spleen, skeletal muscle, lung, brain and thymus.

Knockout studies Knockout mice lacking the ligand binding domain of PPAR-delta are viable. However, these mice are smaller than the wild type both neo and postnatally. In addition, fat stores in the gonads of the mutants are smaller. The mutants also display increased epidermal hyperplasia upon induction with TPA.

Ligands PPAR-delta is activated in the cell by various fatty acids and fatty acid derivatives. Examples of naturally occurring fatty acids that bind with and activate PPAR-delta include arachidonic acid and certain members of the 15-hydroxyicosatetraenoic acid family of arachidonic acid metabolites including 15(S)-HETE, 15(R)-HETE, and 15-HpETE. Several high affinity ligands for PPAR-delta have been developed, including GW501516 and GW0742, which play an important role in research. In one study utilizing such a ligand, it has been shown that agonism of PPARδ changes the body's fuel preference from glucose to lipids. Initially, PPAR-delta agonists were considered promising therapies as an exercise mimetic that could treat metabolic syndrome, and evidence of possible pro-cancer effects subsequently emerged. Clinical development of the class nonetheless continued in other indications: the selective PPAR-delta agonist seladelpar received accelerated approval from the US Food and Drug Administration in August 2024 for primary biliary cholangitis. The atypical antidepressant Tianeptine has been shown to be a high-efficacy PPAR-delta agonist.

Agonists GW501516 GW0742 Seladelpar Telmisartan Tianeptine Estianeptine Although its drug development was discontinued due to animal studies suggesting an increased risk of cancer, GW501516 has been used as a performance enhancing drug. It and other PPAR-delta agonists are banned in sports.

Interactions Peroxisome proliferator-activated receptor delta has been shown to interact with HDAC3 and NCOR2.

References

Illustrations

Worked examples

Example 1 — a first encounter with Peroxisome proliferator-activated receptor delta

Start with the simplest possible case. Write down what Peroxisome proliferator-activated receptor delta claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Peroxisome proliferator-activated receptor delta before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Peroxisome proliferator-activated receptor delta ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Peroxisome proliferator-activated receptor delta

In research: Peroxisome proliferator-activated receptor delta appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Peroxisome proliferator-activated receptor delta in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Peroxisome proliferator-activated receptor delta is common in secondary-school and first-year university syllabi. It links to neighbouring topics Biology of bipolar disorder, Genes on human chromosome 6, Intracellular receptors, so understanding it makes those chapters shorter.
In everyday life: Look for Peroxisome proliferator-activated receptor delta outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Peroxisome proliferator-activated receptor delta in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Peroxisome proliferator-activated receptor delta means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
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Frequently asked questions

What is Peroxisome proliferator-activated receptor delta in simple terms?

Why does Peroxisome proliferator-activated receptor delta matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Peroxisome proliferator-activated receptor delta?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Peroxisome proliferator-activated receptor delta.