Preferred Label : Metabolic Syndrome Pathway;
NCIt related terms : Visceral Fat Deposits and the Metabolic Syndrome;
Alternative definition : BIOCARTA: Obesity is associated with many adverse health effects, including an increased
risk of diabetes and heart disease. The combined condition of obesity, diabetes, and
heart disease is sometimes referred to as the metabolic syndrome. One of the factors
that best correlates obesity with the rest of the metabolic syndrome is not overall
body mass, but the distribution of adipose tissue in the abdominal region, visceral
obesity. Glucocorticoids have been associated as a risk factor for the metabolic syndrome,
but most obese individuals have normal levels of circulating corticosteroids. Active
corticosteroids such as cortisol and corticosterone activate the glucocorticoid receptor,
a nuclear hormone receptor and transcription factor. Obese individuals have elevated
levels in adipose tissue of a key enzyme in glucocorticoid metabolism, 11beta hydroxysteroid
dehydrogenase type 1 (11betaHSD-1). 11betaHSD-1 interconverts inactive corticosteroids
and the active form. When present in cells, 11betaHSD-1 can convert inactive corticosteroids
from the blood to create locally high concentrations in a tissue such as adipose tissue.
When activated in adipose tissue, GR increases the level of visceral fat, induces
insulin resistance and dyslipidemias that increase the risk of heart disease. The
mechanisms by which GR might induce the various aspects of the metabolic syndrome
are a key area of research. One of the genes activated by GR is lipoprotein lipase.
When GR is activated in visceral adipose tissue, it will increase the expression of
lipoprotein lipase (LPL). This enzyme hydrolyzes triglycerides in plasma, releasing
free fatty acids into tissues, where they can be reassembled into triglycerides. In
visceral adipose, this GR-driven overexpression of lipoprotein lipase will result
in the increased deposits of visceral fat that are observed. Genes thought to be involved
in insulin resistance also appear to be affected by altered 11betaHSD-1 corticosteroid
metabolism in visceral fat. This includes downregulation of resistin and adipoQ, and
induction of TNF-alpha. The elevated free fatty acids and active corticosteroids released
from visceral fat may account for the metabolic changes in liver associated with the
metabolic syndrome. Antidiabetic thiazoidinedione drugs such as troglitazone and Avandia
act as agonists of another nuclear receptor, PPAR-gamma. These drugs activate PPAR-gamma
and repress expression of 11betaHSD-1 in visceral tissue, perhaps accounting in part
for the antidiabetic insulin sensitizing properties of these drugs. (This definition
may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_vobesityPathway;
Origin ID : C39268;
UMLS CUI : C1513161;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
