Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038187 (
starvation
)
24,951
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Costello syndrome
is a "RASopathy" that is characterized by growth retardation, dysmorphic facial appearance, hypertrophic cardiomyopathy and tumor predisposition. >80% of patients with
Costello syndrome
harbor a heterozygous germline G12S mutation in HRAS. Altered metabolic regulation has been suspected because patients with
Costello syndrome
exhibit hypoketotic hypoglycemia and increased resting energy expenditure, and their growth is severely retarded. To examine the mechanisms of energy reprogramming by HRAS activation in vivo, we generated knock-in mice expressing a heterozygous Hras G12S mutation (Hras
G12S/+
mice) as a mouse model of
Costello syndrome
. On a high-fat diet, Hras
G12S/+
mice developed a lean phenotype with microvesicular hepatic steatosis, resulting in early death compared with wild-type mice. Under
starvation
conditions, hypoketosis and elevated blood levels of long-chain fatty acylcarnitines were observed, suggesting impaired mitochondrial fatty acid oxidation. Our findings suggest that the oncogenic Hras mutation modulates energy homeostasis in vivo.
...
PMID:Mice with an Oncogenic HRAS Mutation are Resistant to High-Fat Diet-Induced Obesity and Exhibit Impaired Hepatic Energy Homeostasis. 2924 9
