Impairment of adipsin expression is secondary to the onset of obesity in db/db mice

Area of Science:

• Biochemistry
• Genetics
• Obesity Research

Background:

• Genetically obese mice (db/db and ob/ob) are models for human obesity, but primary biochemical defects are unknown.
• Suppressed adipsin expression in adult obese mice suggested a role in obesity pathogenesis.
• For etiological significance, adipsin deficiency must occur early in life during fat accumulation.

Purpose of the Study:

• To investigate the temporal relationship between adipsin expression and adipose tissue development in early-stage db/db mice.
• To determine if early adipsin deficiency contributes to the onset of obesity in this genetic model.

Main Methods:

• Comparison of adipose tissue development in db/db pups and lean (+/db) littermates at 10 days of age.
• Quantification of adipose tissue adipsin mRNA and serum adipsin levels in db/db mice at 10, 15, and 30 days of age.
• Assessment of hyperinsulinemia development in db/db mice.

Main Results:

• At 10 days, db/db pups showed significantly more adipose tissue than lean controls, but with similar adipsin mRNA and serum levels.
• Adipsin expression remained normal in obese mice at 15 days.
• Adipsin deficiency was evident at 30 days, coinciding with the development of hyperinsulinemia.

Conclusions:

• The defect in adipsin expression in db/db mice is a secondary phenomenon.
• Adipsin deficiency does not play a primary etiological role in the onset of obesity in this model.
• Early adipose tissue overdevelopment precedes adipsin suppression in db/db mice.