Several common diseases such as type II diabetes, hypertension, cardiovascular diseases, hyperlipidemia, and some cancers are associated with obesity.
An abnormal increase in body fat relative to lean tissue mass has been used as an indicator of obesity.
High fat diet, certain environmental factors, and genetic linkage are the primary causes of obesity.
In order to understand the genetic basis of obesity, several monogenic murine obesity models have been characterized including obese (Ob), diabetes (db), fat (fat), agouti yellow (Ay), and tubby (tub).
More recently, Tub, the human homolog of mouse Tub, TULP1 & TULP2 (for Tubby Like Proteins) and Agouti related protein (AGRP) have been cloned.
The obesity associated with Ay mice may be due to ectopic expression of a secreted protein Agouti.
Agouti protein (132 aa in human) is normally expressed in skin but its ubiquitous expression causes obesity.
Agouti is a paracrine-signaling molecule that affects pigmentation by inhibiting the melanocortin receptor 1 (MCR-1).
However, recombinant Agouti protein also antagonizes the MC2R and MC4R.
AGRP (132 aa in human, chromosome 16q21) is normally expressed in adrenal and hypothalamus.
AGRP levels are increased several folds in ob/ob mice.
AGRP is a strong antagonist of MC3R and MC4R.
Ubiquitous expression of AGRP in transgenic mice causes obesity without altering skin pigmentation.
Applications:Suitable for use in ELISA.
Western Blot, though not tested, may potentially be used as an application.
