Exposure to an obesity-inducing diet early affects pattern of expression of peroxisome proliferator, retinoic acid, and triiodothyronine nuclear receptors in the rat

Since evidence has appeared that alpha and gamma isoforms of the peroxisome proliferator receptors (PPARs) are involved in the regulation of triglycer ide homeostasis and in the control of the differentiation of adipocytes tha t is required for the development of obesity, a large number of studies hav e investigated the physiologic role of nuclear receptors in the control of energy balance. The aim of this study was to determine the early effects of an obesity-inducing diet on the expression of PPAR alpha and gamma and oth er nuclear receptors such as all-trans retinoic acid receptor (RAR) and tri iodothyronine receptor (TR), which all form functional heterodimers with a common partner, the 9-cis retinoic acid receptor (RXR). The experiment used a cafeteria diet where 60% of the energy was supplied as lipids. This diet was offered to young rats for 8 and 28 days and the expression of nuclear receptors was determined at the end of each experimental time period (1) in the liver by assaying the binding properties of RAR and TR and by quantify ing mRNA levels of RAR beta, TR alpha (1)beta (1), RXR alpha, and PPAR alph a, and (2) in the white adipose tissue (WAT) by quantifying mRNA levels of RAR alpha, RXR alpha, TR alpha (1)beta (1), and PPAR gamma (2). After 8 day s of cafeteria diet a significant decrease of RAR and TR maximal binding ca pacity (MBC) was observed in the liver (-20.1% and -35.0%, respectively, P < .05) and the level of the mRNA of RAR beta was significantly decreased (- 17.4%, P < .05). After 28 days of cafeteria diet, the level of the mRNA of PPAR alpha and acyl-CoA oxidase (ACOX) was significantly increased (+54.5% and +37.8%, P < .01 and P < .05, respectively), whereas the MBC of RAR and TR was significantly decreased (-16.0% and -23.4%, P < .01), as were the mR NA levels of RAR beta and TR alpha (1)beta (1) (-28.5% and -32.0%, P < .05) . The level of RXRa mRNA was unchanged. In WAT, the mRNA level of PPAR gamm a2 was significantly increased after 28 days of cafeteria diet (+49.5%, P < .05) and the mRNA levels of RARa and TR alpha (1)beta (1), significantly d ecreased (-22.3% and -31.0%, P < .05). These results as a whole showed that a high-fat diet can induce early modifications in the pattern of expressio n of nuclear receptors in the liver and the WAT. These modifications could be compatible with an early adaptive phenomenon. Further investigations are necessary to better understanding the link between the modifications of th e pattern of expression of these receptors and plasticity of adipose tissue leading to the onset of obesity. Copyright (C) 2001 by WB. Saunders Compan y.