General Information:

Id: 3,892 (click here to show other Interactions for entry)
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
article
Reference: Ringseis R et al.(2012) Regulation of Genes Involved in Carnitine Homeostasis by PPARalpha across Different Species (Rat, Mouse, Pig, Cattle, Chicken, and Human) PPAR Res 2012 [PMID: 23150726]

Interaction Information:

Comment Peroxisome proliferator-activated receptor alpha (PPARalpha) is considered a master transcriptional regulator of lipid metabolism and energy homeostasis, because typical genes regulated by PPARalpha are involved in all aspects of fatty acid catabolism (cellular fatty acid uptake, activation of fatty acids, intracellular fatty acid transport, import of fatty acids into the mitochondria, and mitochondrial and peroxisomal fatty acid beta-oxidation), ketogenesis, as well as gluconeogenesis.
Formal Description
Interaction-ID: 39368

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Peroxisome proliferator-activated receptor alpha (PPARalpha) is considered a master transcriptional regulator of lipid metabolism and energy homeostasis, because typical genes regulated by PPARalpha are involved in all aspects of fatty acid catabolism (cellular fatty acid uptake, activation of fatty acids, intracellular fatty acid transport, import of fatty acids into the mitochondria, and mitochondrial and peroxisomal fatty acid beta-oxidation), ketogenesis, as well as gluconeogenesis.
Formal Description
Interaction-ID: 39370

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Peroxisome proliferator-activated receptor alpha (PPARalpha) is considered a master transcriptional regulator of lipid metabolism and energy homeostasis, because typical genes regulated by PPARalpha are involved in all aspects of fatty acid catabolism (cellular fatty acid uptake, activation of fatty acids, intracellular fatty acid transport, import of fatty acids into the mitochondria, and mitochondrial and peroxisomal fatty acid beta-oxidation), ketogenesis, as well as gluconeogenesis.
Formal Description
Interaction-ID: 39371

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment Peroxisome proliferator-activated receptor alpha (PPARalpha) is considered a master transcriptional regulator of lipid metabolism and energy homeostasis, because typical genes regulated by PPARalpha are involved in all aspects of fatty acid catabolism (cellular fatty acid uptake, activation of fatty acids, intracellular fatty acid transport, import of fatty acids into the mitochondria, and mitochondrial and peroxisomal fatty acid beta-oxidation), ketogenesis, as well as gluconeogenesis.
Formal Description
Interaction-ID: 39372

gene/protein

PPARA

affects_activity of

process

gluconeogenesis

Drugbank entries Show/Hide entries for PPARA
Comment It was shown that elevation of hepatic carnitine concentration in response to fasting, or fibrates occurs only in wild-type mice but not in transgenic mice lacking a functional PPARalpha protein strengthening the assumption that PPARalpha is a critical regulator of carnitine homeostasis.
Formal Description
Interaction-ID: 39378

gene/protein

PPARA

increases_quantity of

drug/chemical compound

Carnitine

in liver
Drugbank entries Show/Hide entries for PPARA
Comment It was shown that elevation of hepatic carnitine concentration in response to fasting, or fibrates occurs only in wild-type mice but not in transgenic mice lacking a functional PPARalpha protein strengthening the assumption that PPARalpha is a critical regulator of carnitine homeostasis.
Formal Description
Interaction-ID: 39379

gene/protein

PPARA

affects_activity of

Drugbank entries Show/Hide entries for PPARA
Comment It could be convincingly demonstrated that the mouse genes encoding the carnitine transporter novel organic cation transporter 2 (OCTN2/SLC22A5) and two enzymes of the carnitine biosynthetic pathway, gamma-butyrobetaine dioxygenase (BBOX1) and 4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1), are direct PPARalpha target genes as evidenced by the identification of functional peroxysome proliferator responsive elements (PPRE) within the regulatory region of the respective genes.
Formal Description
Interaction-ID: 39380

gene/protein

PPARA

increases_expression of

gene/protein

SLC22A5

Drugbank entries Show/Hide entries for PPARA or SLC22A5
Comment It could be convincingly demonstrated that the mouse genes encoding the carnitine transporter novel organic cation transporter 2 (OCTN2/SLC22A5) and two enzymes of the carnitine biosynthetic pathway, gamma-butyrobetaine dioxygenase (BBOX1) and 4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1), are direct PPARalpha target genes as evidenced by the identification of functional peroxysome proliferator responsive elements (PPRE) within the regulatory region of the respective genes.
Formal Description
Interaction-ID: 39382

gene/protein

PPARA

increases_expression of

gene/protein

BBOX1

Drugbank entries Show/Hide entries for PPARA or BBOX1
Comment It could be convincingly demonstrated that the mouse genes encoding the carnitine transporter novel organic cation transporter 2 (OCTN2/SLC22A5) and two enzymes of the carnitine biosynthetic pathway, gamma-butyrobetaine dioxygenase (BBOX1) and 4-trimethylaminobutyraldehyde dehydrogenase (ALDH9A1), are direct PPARalpha target genes as evidenced by the identification of functional peroxysome proliferator responsive elements (PPRE) within the regulatory region of the respective genes.
Formal Description
Interaction-ID: 39383

gene/protein

PPARA

increases_expression of

gene/protein

ALDH9A1

Drugbank entries Show/Hide entries for PPARA or ALDH9A1
Comment It is well established that PPARalpha activators exert distinct species-specific actions. In rodents, like mice and rats, administration of PPARalpha activators leads to a marked peroxisomal enzyme induction, peroxisome proliferation, and even hepatocarcinogenesis. In contrast, PPARalpha activators cannot induce peroxisome proliferation and hepatocarcinogenesis and the induction of peroxisomal metabolism pathways is much less pronounced in human hepatocytes and livers from nonhuman primates. This distinct response of the peroxisomes to PPARalpha activators is responsible for the classification of different species into proliferating (mice, rats) and nonproliferating ones (humans, monkeys, guinea pigs). Several factors are considered to account for the marked difference in the response to PPARalpha activators between different species: expression level of PPARalpha, degree of conservation and functionality of the PPRE in the regulatory region of target genes, and lack or overexpression of transcriptional coregulators.
Formal Description
Interaction-ID: 39384

gene/protein

PPARA

affects_activity of

in rodents
Drugbank entries Show/Hide entries for PPARA
Comment It is well established that PPARalpha activators exert distinct species-specific actions. In rodents, like mice and rats, administration of PPARalpha activators leads to a marked peroxisomal enzyme induction, peroxisome proliferation, and even hepatocarcinogenesis. In contrast, PPARalpha activators cannot induce peroxisome proliferation and hepatocarcinogenesis and the induction of peroxisomal metabolism pathways is much less pronounced in human hepatocytes and livers from nonhuman primates. This distinct response of the peroxisomes to PPARalpha activators is responsible for the classification of different species into proliferating (mice, rats) and nonproliferating ones (humans, monkeys, guinea pigs). Several factors are considered to account for the marked difference in the response to PPARalpha activators between different species: expression level of PPARalpha, degree of conservation and functionality of the PPRE in the regulatory region of target genes, and lack or overexpression of transcriptional coregulators.
Formal Description
Interaction-ID: 39388

gene/protein

PPARA

affects_activity of

in rodents
Drugbank entries Show/Hide entries for PPARA
Comment It is well established that PPARalpha activators exert distinct species-specific actions. In rodents, like mice and rats, administration of PPARalpha activators leads to a marked peroxisomal enzyme induction, peroxisome proliferation, and even hepatocarcinogenesis. In contrast, PPARalpha activators cannot induce peroxisome proliferation and hepatocarcinogenesis and the induction of peroxisomal metabolism pathways is much less pronounced in human hepatocytes and livers from nonhuman primates. This distinct response of the peroxisomes to PPARalpha activators is responsible for the classification of different species into proliferating (mice, rats) and nonproliferating ones (humans, monkeys, guinea pigs). Several factors are considered to account for the marked difference in the response to PPARalpha activators between different species: expression level of PPARalpha, degree of conservation and functionality of the PPRE in the regulatory region of target genes, and lack or overexpression of transcriptional coregulators.
Formal Description
Interaction-ID: 39396

gene/protein

PPARA

NOT affects_activity of

in humans
Drugbank entries Show/Hide entries for PPARA
Comment It is well established that PPARalpha activators exert distinct species-specific actions. In rodents, like mice and rats, administration of PPARalpha activators leads to a marked peroxisomal enzyme induction, peroxisome proliferation, and even hepatocarcinogenesis. In contrast, PPARalpha activators cannot induce peroxisome proliferation and hepatocarcinogenesis and the induction of peroxisomal metabolism pathways is much less pronounced in human hepatocytes and livers from nonhuman primates. This distinct response of the peroxisomes to PPARalpha activators is responsible for the classification of different species into proliferating (mice, rats) and nonproliferating ones (humans, monkeys, guinea pigs). Several factors are considered to account for the marked difference in the response to PPARalpha activators between different species: expression level of PPARalpha, degree of conservation and functionality of the PPRE in the regulatory region of target genes, and lack or overexpression of transcriptional coregulators.
Formal Description
Interaction-ID: 39397

gene/protein

PPARA

NOT affects_activity of

in humans
Drugbank entries Show/Hide entries for PPARA
Comment Genes encoding proteins of the carnitine shuttle system, such as carnitine-palmitoyltransferase I and carnitine-acylcanitine translocase, were shown to be regulated by both PPARalpha and PPARdelta.
Formal Description
Interaction-ID: 39461

gene/protein

PPARA

affects_expression of

gene/protein

CPT1A

Drugbank entries Show/Hide entries for PPARA or CPT1A
Comment Genes encoding proteins of the carnitine shuttle system, such as carnitine-palmitoyltransferase I and carnitine-acylcanitine translocase, were shown to be regulated by both PPARalpha and PPARdelta.
Formal Description
Interaction-ID: 39463

gene/protein

PPARA

affects_expression of

gene/protein

CPT1B

Drugbank entries Show/Hide entries for PPARA
Comment Genes encoding proteins of the carnitine shuttle system, such as carnitine-palmitoyltransferase I and carnitine-acylcanitine translocase, were shown to be regulated by both PPARalpha and PPARdelta.
Formal Description
Interaction-ID: 39464

gene/protein

PPARA

affects_expression of

gene/protein

CPT1C

Drugbank entries Show/Hide entries for PPARA
Comment Genes encoding proteins of the carnitine shuttle system, such as carnitine-palmitoyltransferase I and carnitine-acylcanitine translocase, were shown to be regulated by both PPARalpha and PPARdelta.
Formal Description
Interaction-ID: 39465

gene/protein

PPARA

affects_expression of

gene/protein

SLC25A20

Drugbank entries Show/Hide entries for PPARA or SLC25A20