Objective: To gain insight into the in vivo modulation of the expression of the adipogenic transcription factors PPAR gamma 2, C/EBP alpha, and ADD1/SREBP1c by retinoids and its relationship with whole-body adiposity.
Research methods and procedures: Three-week-old mice were fed with standard chow or a vitamin A-deficient diet for 10 weeks. During the 4 days immediately before they were killed, the animals were treated either with all-trans retinoic acid (tRA; 100 mg/kg per day, subcutaneously) or vehicle. The specific levels of the mRNAs for the three transcription factors were analyzed in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue and in brown adipose tissue (BAT). Other parameters determined were leptin and UCP2 levels in white adipose tissue depots, total cholesterol and triglyceride serum levels, energy intake, body weight, and adiposity.
Results: Vitamin A-deficient diet feeding led to a marked increase of adiposity and to a small increase of body weight. Hypertrophy of white adipose tissue depots correlated with enhanced PPAR gamma 2 expression. Hypertrophy of BAT, in contrast, correlated with a decrease of PPAR gamma 2 expression that may contribute to the known reduced thermogenic potential of BAT under conditions of vitamin A restriction. Treatment with tRA triggered a reduction of adiposity and body weight that correlated with a down-regulation of PPAR gamma 2 expression in all adipose tissues. The effects of tRA were more pronounced in eWAT, where C/EBP alpha and ADD1/SREBP1c levels were also reduced. The response to tRA was impaired in the eWAT and BAT of animals fed the vitamin A-deficient diet.
Discussion: The results emphasize the importance of retinoids as physiological regulators of adipose tissue development and function in intact animals.