Disease relevance of Dob1

• We describe a new multiple gene mouse model of differential sensitivity to dietary obesity that provides a tool for dissecting the genetic basis for body composition and obesity [1].
• Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance [2].
• Among a selected group of mouse strains susceptible to dietary obesity, those with an enhanced capacity for Ucp1 and brown adipocyte induction in white fat preferentially lost body weight following adrenergic stimulation [3].

High impact information on Dob1

• Absence of the lipid phosphatase SHIP2 confers resistance to dietary obesity [4].
• The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes [5].
• Dietary obesity linked to genetic loci on chromosomes 9 and 15 in a polygenic mouse model [6].
• Intercrosses between these strains segregate the phenotype of sensitivity to dietary obesity [6].
• Loci linked to sensitivity to dietary obesity were identified by Quantitative Trait Locus (QTL) analysis of two mapping populations derived from a cross between AKR/J and SWR/J mice [6].

Biological context of Dob1

• This study suggests that loss of PKCtheta reduces energy expenditure and increases the risk of dietary obesity and insulin resistance in mice [7].

Anatomical context of Dob1

• We recently reported that UCP2 expression is increased by high fat feeding in adipose tissue of the A/J strain of mice, which is resistant to the development of dietary obesity [8].

Associations of Dob1 with chemical compounds

• In one model of dietary obesity resulting when animals eat a high-fat diet, the syndrome is blocked by inhibitory adrenal steroid activity [9].

Other interactions of Dob1

• CONCLUSIONS: Impaired expression of adipocyte betaAR subtypes is a general feature of both genetic and dietary obesity in mice [10].
• Indeed, mice deficient in 11beta-HSD1 resist both the metabolic syndrome that develops with dietary obesity and glucocorticoid-associated cognitive impairments that develop with ageing [11].
• Obese human and rodent models of dietary obesity have shown decreased sensitivity to blood-borne leptin, postulated to be due to impaired transport of leptin across the BBB [12].

References