biology

Peroxisome proliferator-activated receptor gamma

Peroxisome proliferator-activated receptor gamma 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 gamma rather than just read about it. In short: Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the PPARG gene. Tissue distribution PPARG is mainly present in adipose tissue, colon and macrophages.

Key takeaways

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Reference excerpt

Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the PPARG gene.

Tissue distribution PPARG is mainly present in adipose tissue, colon and macrophages. Two isoforms of PPARG are detected in the human and in the mouse: PPAR-γ1 (found in nearly all tissues except muscle) and PPAR-γ2 (mostly found in adipose tissue and the intestine).

Gene expression This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Alternatively spliced transcript variants that encode different isoforms have been described. The activity of PPARG can be regulated via phosphorylation through the MEK/ERK pathway. This modification decreases transcriptional activity of PPARG and leads to diabetic gene modifications, and results in insulin insensitivity. For example, the phosphorylation of serine 112 will inhibit PPARG function, and enhance adipogenic potential of fibroblasts.

Function PPARG regulates fatty acid storage and glucose metabolism. The genes activated by PPARG stimulate lipid uptake and adipogenesis by fat cells. PPARG knockout mice are devoid of adipose tissue, establishing PPARG as a master regulator of adipocyte differentiation. PPARG increases insulin sensitivity by enhancing storage of fatty acids in fat cells (reducing lipotoxicity), by enhancing adiponectin release from fat cells, by inducing FGF21, and by enhancing nicotinic acid adenine dinucleotide phosphate production through upregulation of the CD38 enzyme in mice. PPARG promotes anti-inflammatory M2 macrophage activation in mice. Adiponectin induces ABCA1-mediated reverse cholesterol transport by activation of PPAR-γ and LXRα/β. Many naturally occurring agents directly bind with and activate PPAR gamma. These agents include various polyunsaturated fatty acids like arachidonic acid and arachidonic acid metabolites such as certain members of the 5-hydroxyicosatetraenoic acid and 5-oxo-eicosatetraenoic acid family, e.g., 5-oxo-15(S)-HETE and 5-oxo-ETE or 15-hydroxyicosatetraenoic acid family including 15(S)-HETE, 15(R)-HETE, and 15(S)-HpETE, the phytocannabinoid tetrahydrocannabinol (THC), its metabolite THC-COOH, and its synthetic analog ajulemic acid (AJA). The activation of PPAR gamma by these and other ligands may be responsible for inhibiting the growth of cultured human breast, gastric, lung, prostate and other cancer cell lines. During embryogenesis, PPARG first substantially expresses in the interscapular brown fat pad in mice. Depletion of PPARG in mice results in embryonic lethality at E10.5, due to the vascular anomalies in placenta, with no permeation of fetal blood vessels and dilation and rupture of maternal blood sinuses. The expression of PPARG can be detected in mouse placenta as early as E8.5 and through the remainder of gestation; in the human placenta, PPARG is mainly located in the primary trophoblast cell. PPARG is required for epithelial differentiation of trophoblast tissue in mice, which is critical for proper placenta vascularization. PPARG agonists inhibit extravillous cytotrophoblast invasion. PPARG is also required for the accumulation of lipid droplets by the placenta in mice.

Interactions Peroxisome proliferator-activated receptor gamma has been shown to interact with:

Research PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia. Many insulin sensitizing drugs (namely, the thiazolidinediones) used in the treatment of diabetes activate PPARG as a means to lower serum glucose without increasing pancreatic insulin secretion. Activation of PPARG is more effective for skeletal muscle insulin resistance than for insulin resistance of the liver.

See also Endocannabinoid system Endocannainoidome

References

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Illustrations

Worked examples

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

Start with the simplest possible case. Write down what Peroxisome proliferator-activated receptor gamma 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 gamma 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 gamma 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 gamma

In research: Peroxisome proliferator-activated receptor gamma 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 gamma 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 gamma is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 3, Intracellular receptors, Transcription factors, so understanding it makes those chapters shorter.
In everyday life: Look for Peroxisome proliferator-activated receptor gamma 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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Frequently asked questions

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

Why does Peroxisome proliferator-activated receptor gamma 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 gamma?

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 gamma.