P53 regulates the lipid metabolism response to metabolic stress in brown adipose tissue

Einleitung Obesity and metabolic dysfunction are highly prevalent worldwide and are associated with increased risk for type 2 diabetes and cardiovascular disease. Brown adipose tissue (BAT) possesses significant potential due its ability for uncoupled respiration and is investigated as a therapeutic target. In addition to its role as a tumour suppressor, p53 is described as a regulator of metabolism in non-transformed cells, and the role of p53 in nutrient flux regulation of adipose tissue is not well understood.

Methoden Acute, BAT-specific p53 knockout (p53BKO) mice were generated using the tamoxifen-inducible Cre-loxP-system. Control and p53BKO mice were subjected to fasting or adrenergic activation to investigate the functional role of p53 in directing brown adipocyte nutrient oxidation.

Ergebnisse p53BKO mice demonstrated changed lipid metabolism in BAT and, unexpectedly, also in white fat. Furthermore, the response to acute adrenergic stimulation was blunted in p53BKO mice, which displayed altered systemic triglyceride metabolism and lipid mobilisation.

Schlussfolgerung Taken together, these data suggest that p53 is an integral part of acute lipid metabolism regulation in BAT. Further investigation will be important in understanding the implication of p53 in nutrient turnover in the context of obesity and metabolic stress.

Publication History

Article published online:
04 September 2020