General Information:

Id: 1,963
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Rattus norvegicus
male
article
Reference: Koves TR et al.(2008) Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 7: 45-56 [PMID: 18177724]

Interaction Information:

Comment Total serum nonesterified free fatty acids (NEFA) were elevated in response to an overnight fast and prolonged high-fat (HF) feeding; however, the diet-induced increase was apparent only in the postprandial state. Oleate (C18:1), palmitate (C16:0), linoleate (C18:2), and stearate (C18:0) were the most elevated fatty acids in HF-fed animals.
Formal Description
Interaction-ID: 15312

environment

high-fat diet

increases_quantity of

drug/chemical compound

Fatty acid

in blood; in postprandial state
Comment Total serum nonesterified free fatty acids (NEFA) were elevated in response to an overnight fast and prolonged high-fat (HF) feeding; however, the diet-induced increase was apparent only in the postprandial state. Oleate (C18:1), palmitate (C16:0), linoleate (C18:2), and stearate (C18:0) were the most elevated fatty acids in HF-fed animals.
Formal Description
Interaction-ID: 15395

environment

high-fat diet

increases_quantity of

drug/chemical compound

Oleic acid

in blood; in postprandial state
Drugbank entries Show/Hide entries for
Comment Total serum nonesterified free fatty acids (NEFA) were elevated in response to an overnight fast and prolonged high-fat (HF) feeding; however, the diet-induced increase was apparent only in the postprandial state. Oleate (C18:1), palmitate (C16:0), linoleate (C18:2), and stearate (C18:0) were the most elevated fatty acids in HF-fed animals.
Formal Description
Interaction-ID: 15396

environment

high-fat diet

increases_quantity of

drug/chemical compound

Palmitic acid

in blood; in postprandial state
Drugbank entries Show/Hide entries for
Comment Total serum nonesterified free fatty acids (NEFA) were elevated in response to an overnight fast and prolonged high-fat (HF) feeding; however, the diet-induced increase was apparent only in the postprandial state. Oleate (C18:1), palmitate (C16:0), linoleate (C18:2), and stearate (C18:0) were the most elevated fatty acids in HF-fed animals.
Formal Description
Interaction-ID: 15397

environment

high-fat diet

increases_quantity of

drug/chemical compound

Linoleic acid

in blood; in postprandial state
Comment Total serum nonesterified free fatty acids (NEFA) were elevated in response to an overnight fast and prolonged high-fat (HF) feeding; however, the diet-induced increase was apparent only in the postprandial state. Oleate (C18:1), palmitate (C16:0), linoleate (C18:2), and stearate (C18:0) were the most elevated fatty acids in HF-fed animals.
Formal Description
Interaction-ID: 15398

environment

high-fat diet

increases_quantity of

drug/chemical compound

Stearic acid

in blood; in postprandial state
Drugbank entries Show/Hide entries for
Comment In response to overnight fasting, in serum most lipid-derived acylcarnitines increased, whereas the amino acid intermediates decreased. Consistent with the fasting-induced rise in circulating NEFA, this profile implies a metabolic switch favoring higher rates of beta-oxidation and diminished degradation of amino acids.
Formal Description
Interaction-ID: 15399

environment

fasting

increases_activity of

Comment In response to overnight fasting, in serum most lipid-derived acylcarnitines increased, whereas the amino acid intermediates decreased. Consistent with the fasting-induced rise in circulating NEFA, this profile implies a metabolic switch favoring higher rates of beta-oxidation and diminished degradation of amino acids.
Formal Description
Interaction-ID: 15400

environment

fasting

decreases_activity of

Comment Under fasting conditions, serum acylcarnitines were similar between the two diet groups. Conversely, serum samples collected in the fed state revealed higher levels of several fatty acid-derived species and reduced levels of C3, C4, and C5 in HF-fed animals compared to SC-fed animals.
Formal Description
Interaction-ID: 15401

environment

high-fat diet

increases_activity of

Comment Consistent with the serum profile, a marked accumulation of fatty acylcarnitine species in muscles from HF-fed rats was observed. Whereas SC-fed rats lowered most muscle fatty acylcarnitines during the transition from the fasted to the fed state, HF-fed animals exhibited little or no change. Thus, during fasted conditions, the import of fatty acids into muscle mitochondria appears to exceed metabolic demand. Feeding relieved the surplus, but only in the SC-fed group, suggesting that mitochondria from obese animals are unable to appropriately adjust fatty acid influx in response to nutritional status.
Formal Description
Interaction-ID: 15402

environment

high-fat diet

increases_activity of

in skeletal muscle
Comment In contrast to skeletal muscle, liver acylcarnitines were not elevated in HF-fed animals compared to SC-fed animals.
Formal Description
Interaction-ID: 15403

environment

high-fat diet

NOT increases_activity of

in liver
Comment In standard chow (SC)-fed rats, long-chain acylcarnitine levels increased during the fed-to-fasted transition, consistent with increased CPT1 activity, whereas this response was impaired in the HF-fed group.
Formal Description
Interaction-ID: 15404

environment

chow diet

increases_activity of

gene/protein

CPT1A

in liver
Drugbank entries Show/Hide entries for CPT1A
Comment In standard chow (SC)-fed rats, long-chain acylcarnitine levels increased during the fed-to-fasted transition, consistent with increased CPT1 activity, whereas this response was impaired in the HF-fed group.
Formal Description
Interaction-ID: 15406

environment

high-fat diet

NOT increases_activity of

gene/protein

CPT1A

in liver
Drugbank entries Show/Hide entries for CPT1A
Comment Fasting-induced upregulation of CPT1-alpha (the liver isoform) was abolished by HF feeding.
Formal Description
Interaction-ID: 15407

environment

fasting

increases_expression of

gene/protein

CPT1A

in liver; after chow diet
Drugbank entries Show/Hide entries for CPT1A
Comment Fasting-induced upregulation of CPT1-alpha (the liver isoform) was abolished by HF feeding.
Formal Description
Interaction-ID: 15408

environment

fasting

NOT increases_expression of

gene/protein

CPT1A

in liver; after high-fat diet
Drugbank entries Show/Hide entries for CPT1A
Comment High-fat feeding promotes incomplete beta-oxidation and metabolic inflexibility in skeletal muscle.
Formal Description
Interaction-ID: 15409

environment

high-fat diet

increases_activity of

process

incomplete fatty acid beta-oxidation

in skeletal muscle
Comment In cultured L6 myotubes, lipid-induced insulin resistance was prevented by manipulations that restrict fatty acid uptake into mitochondria. Insulin resistance in L6 myocytes requires beta-oxidation.
Formal Description
Interaction-ID: 15411

increases_activity of

disease

Insulin resistance

in skeletal muscle