Impairment of nutritional regulation of adipose triglyceride lipase expression with age

Objective: Fasting-induced lipolysis becomes less effective with age. We have studied whether nutritional regulation of adipose triglyceride lipase (ATGL)-with an important role in lipolysis in low energy states-is affected by age. Design: Wistar rats of different ages (from 1 to 13 months) were distributed in control and fasted groups (14 h-food deprivation). ATGL mRNA expression was measured in different adipose depots at different ages and in only one depot at 13 months by reverse transcription (RT)-PCR. ATGL protein levels were determined at 3 and 7 months (not at 13 months) by western blot. Nonesterified fatty acid (NEFA), insulin and leptin levels were assessed in serum by enzymatic assays. Results: ATGL expression was dependent on regional fat distribution, with higher levels in brown than in white adipose tissue depots; and was affected by age: ATGL mRNA was increased with age in the brown adipose tissue and was decreased in two of the studied white depots, the inguinal and retroperitoneal, not being affected in the epididymal and mesenteric. Age also affected ATGL nutritional regulation: fasting increased ATGL gene expression and protein levels in the different white adipose depots of the youngest rats (up to the age of 5 months), whereas there was no change in the oldest rats studied (7 and 13-months old). This was in agreement with the pattern of NEFA levels, which did not increase in serum of fasted rats in the oldest animals, whereas other homeostatic parameters, such as insulin and leptin, responded to fasting independently of age. ATGL expressed by brown adipose tissue was not affected by feeding conditions at any age. Conclusion: Nutritional regulation of ATGL expression in white adipose tissue is impaired with age, which could contribute to the increased difficulty for mobilizing lipids when animals are exposed to nutritional stress such as fasting.