Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family

Background: Adiponutrin/PNPLA3 and adipose triglyceride lipase (ATGL) are proteins highly expressed in adipose tissue which have apparently different roles (lipogenic/lipolytic). Gene expression of both proteins and their nutritional regulation have been described to be altered in genetically obese animals. Methods: We studied adiponutrin and ATGL expression in 6-month-old rats made obese by cafeteria diet feeding, submitted to different feeding conditions (feeding/fasting/re-feeding), compared with normoweight animals. Adiponutrin and ATGL mRNA levels were determined in white adipose tissue depots (subcutaneous and visceral) and in interscapular brown adipose tissue, and ATGL protein levels in selected depots. In addition, basal adiponutrin and ATGL expression levels were compared between 6- and 3-month-old animals. Results: Obesity decreased adiponutrin and ATGL expression in different adipose depots. For adiponutrin, a tendency to lower mRNA levels was observed in the white adipose depots studied in obese animals, although the decrease was only significant in the subcutaneous depot. For ATGL, a generalized and significant lower expression was found in white and brown adipose tissue of cafeteria-obese rats. When considering nutritional regulation, according to a lipogenic role, adiponutrin mRNA expression decreased with fasting and was recovered by re-feeding in normoweight animals; this regulation was lost in obese rats. Expression of the lipolytic ATGL (mRNA and protein levels) was increased by fasting in normoweight animals in the mesenteric adipose depot, while no change was evident in obese rats. Moreover, adiponutrin and ATGL nutritional regulation was affected by age, and we report a downregulation of adiponutrin mRNA basal levels with age in internal adipose depots. Conclusions: Cafeteria diet-induced obesity and age alter adiponutrin and ATGL expression and their regulation by feeding conditions. These results reinforce the importance of a proper expression and regulation of both proteins for body weight maintenance and their role in energy metabolism.