What does PPAR-alpha do?

Published on by Paul Reynolds

What does PPAR-alpha do?

Peroxisome proliferator-activated receptor (PPAR)-alpha is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPAR-alpha regulates the expression of genes involved in fatty acid beta-oxidation and is a major regulator of energy homeostasis.

Where are PPAR-alpha receptors?

In rodents, highest mRNA expression levels of PPAR-alpha are found in liver and brown adipose tissue, followed by heart and kidney. Lower PPAR-alpha expression levels are found in small and large intestine, skeletal muscle and adrenal gland.

Which drug activates PPAR-alpha?

PPARs are activated by fatty acids and eicosanoids [21], as well as by small molecules, such as fibrates for PPAR-α, GW501516, GW0742, bezafibrate and Telmisartan for PPAR-β/δ, and glitazones for PPAR-γ.

Which drug is PPAR-alpha agonist?

PPAR-alpha agonists PPARα (alpha) is the main target of fibrate drugs, a class of amphipathic carboxylic acids (clofibrate, gemfibrozil, ciprofibrate, bezafibrate, and fenofibrate).

What is Pparα What is its clinical significance?

PPARα is highly expressed in metabolically active tissues, such as liver, heart, skeletal muscle, intestinal mucosa and brown adipose tissue. This receptor is implicated in fatty acid metabolism and its activation lowers lipid levels [12-15].

How do PPAR alpha agonists work?

PPARγ agonists promote adipocyte differentiation, and they promote FFA uptake and storage in subcutaneous adipose rather than visceral adipose tissue. This reduces FFA levels, with associated reductions in insulin resistance.

What is PPAR medicine?

Pioglitazone decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is a potent and highly selective agonist for Peroxisome proliferator-activated receptor-gamma (PPARγ).

Which drugs are fibrates?

List of Fibric acid derivatives:

Drug Name Avg. Rating Reviews
TriCor (Pro) Generic name: fenofibrate 5.9 15 reviews
Lopid (Pro) Generic name: gemfibrozil 6.5 6 reviews
Lipofen (Pro) Generic name: fenofibrate 7.3 2 reviews
Antara (Pro) Generic name: fenofibrate 2.0 1 review

Which activity is mainly performed by Alpha oxidation process?

Alpha oxidation (α-oxidation) is a process by which certain fatty acids are broken down by removal of a single carbon from the carboxyl end. In humans, alpha-oxidation is used in peroxisomes to break down dietary phytanic acid, which cannot undergo beta-oxidation due to its β-methyl branch, into pristanic acid.

What are the benefits of PPAR?

Treatment with PPAR agonists can reduce the burden of atherogenic postprandial lipoproteins and improve vascular function, reduce inflammation and inhibit foam cell formation. All of these would be expected to have favorable effects on cardiovascular risk.

What are the target genes of PPAR alpha?

Gene expression profiling studies have indicated that PPAR-alpha target genes number in the hundreds. Classical target genes of PPAR-alpha include PDK4, ACOX1, and CPT1.

What is the role of peroxisome proliferator activated receptor alpha?

The peroxisome proliferator-activated receptor alpha (PPAR ) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis.

How is PPAR-alpha related to anticonvulsants?

PPAR-alpha may also be a site of action of certain anticonvulsants. PPAR-α governs biological processes by altering the expression of a large number of target genes. Accordingly, the functional role of PPAR-alpha is directly related to the biological function of its target genes.

What is the function of PPAR alpha in the liver?

Function. PPAR-alpha is a transcription factor and a major regulator of lipid metabolism in the liver. PPAR-alpha is activated under conditions of energy deprivation and is necessary for the process of ketogenesis, a key adaptive response to prolonged fasting. Activation of PPAR-alpha promotes uptake, utilization,…

What does PPAR-alpha do?

Peroxisome proliferator-activated receptor (PPAR)-alpha is a ligand-activated transcriptional factor that belongs to the family of nuclear receptors. PPAR-alpha regulates the expression of genes involved in fatty acid beta-oxidation and is a major regulator of energy homeostasis.

Where is PPAR-alpha found?

In rodents, highest mRNA expression levels of PPAR-alpha are found in liver and brown adipose tissue, followed by heart and kidney. Lower PPAR-alpha expression levels are found in small and large intestine, skeletal muscle and adrenal gland.

What drug activates PPAR-alpha?

PPAR alpha, agonists

Drug Target Type
Elafibranor Peroxisome proliferator-activated receptor gamma target
Muraglitazar Peroxisome proliferator-activated receptor alpha target
Muraglitazar Peroxisome proliferator-activated receptor gamma target
Muraglitazar Cytochrome P450 1A2 enzyme

What activates PPAR gamma?

The phytocannabinoid cannabidiol (CBD) has been shown to activate PPAR gamma in in vitro and in vivo models. The cannabinoid carboxylic acids THCA, CBDA and CBGA activate PAARy more efficient than their decarboxylated products; however, THCA was the acid found with highest activity.

How do PPAR alpha agonists work?

PPARγ agonists promote adipocyte differentiation, and they promote FFA uptake and storage in subcutaneous adipose rather than visceral adipose tissue. This reduces FFA levels, with associated reductions in insulin resistance.

Is Metformin a PPAR agonist?

Metformin, although not a PPAR agonist, is also commonly used in the treatment of type 2 diabetes.

What is the role of PPAR gamma?

Activation of PPAR-γ causes insulin sensitization and enhances glucose metabolism, whereas activation of PPAR-β/δ enhances fatty acids metabolism. Thus, PPAR family of nuclear receptors plays a major regulatory role in energy homeostasis and metabolic function.

How is PPAR activated?

Physiological function All PPARs heterodimerize with the retinoid X receptor (RXR) and bind to specific regions on the DNA of target genes. These DNA sequences are termed PPREs (peroxisome proliferator hormone response elements). In contrast, PPARα is activated by leukotriene B4.

How does PPAR gamma increase insulin sensitivity?

PPAR-γ agonists decrease circulating triglyceride and free fatty acid levels by repartitioning fatty acids in adipocytes. Increased free fatty acids are associated with hepatic insulin resistance, resulting in the increased gluconeogenesis (47).

What is the role of PPARα in liver metabolism?

Objective Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD).

How does PPARs and nonalcoholic fatty liver disease differ?

PPARs and nonalcoholic fatty liver disease Nonalcoholic fatty liver disease (NAFLD) encompasses a range of liver pathology ranging from simple steatosis to varying degrees of inflammation, hepatocyte injury and fibrosis. Without intervention it can progress to end-stage liver disease and hepatocellular carcinoma. Given its close association …

Which is peroxisome proliferator activated receptor α ( PPARα )?

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor belonging, together with PPARγ and PPARβ/δ, to the NR1C nuclear receptor subfamily. Many PPARα target genes are involved in fatty acid metabolism in tissues with high oxidative rates such as muscle, heart and liver.

How does the deletion of PPAR alpha affect cisplatin?

PPAR-alpha Deletion Attenuates Cisplatin Nephrotoxicity by Modulating Renal Organic Transporters MATE-1 and OCT-2. PPARalpha/RXRalpha downregulates amino acid catabolism in the liver via interaction with HNF4alpha promoting its proteasomal degradation.