ESPE2022 Free Communications Fat, Metabolism and Obesity (6 abstracts)
Background and Aim: Pediatric patients with germline mutations in the phosphatase and tensin homolog (Pten) gene frequently develop aberrant adipose tissue growth called lipomas. In severe cases, recurrent lipoma formation can have adverse effects on organ function and quality of life. Due to the lack of understanding the basis of lipoma development, no systemic treatment options are available. We therefore aimed to characterize an already described lipoma bearing mouse model with conditional knockout of Pten in osteoprogenitor cells. Surprisingly, these mice did not develop lipomas, but showed an age-dependent decrease in adipose tissue weight.
Methods: We compared metabolic characteristics and adipose tissue histology of mice with inducible knockout of Pten (Pten cKO) in osteoprogenitor cells expressing the transcription factor Osterix/Sp7 and respective control mice. We analyzed lipolysis induction in isolated adipocytes from Pten cKO mice and controls as well as corresponding signaling pathway activation on protein level.
Results: We found an age-dependent loss of fat mass in Pten cKO mice affecting specifically the inguinal as well as gonadal white adipose tissue (WAT) depots, with no observable effect on brown adipose tissue. Other metabolically active organs were not affected by atrophic changes and no change in body weight was observed. When analyzing Pten expression we found an expected decrease of Pten protein in the bone marrow. Surprisingly, we also observed a higher expression of Pten specifically in WAT with concomitant downregulation of AKT phosphorylation, a downstream target of Pten action. Phosphorylation of hormone sensitive lipase (Hsl/Lipe) was increased in Pten cKO WAT. In line with this, we saw a higher release of glycerol from adipocytes isolated from Pten cKO mice compared to control adipocytes. Adipose tissue histology revealed distinct morphological differences between Pten cKO mice and controls. White adipocytes of Pten cKO mice were significantly smaller compared to those from control mice. Interestingly, Pten cKO WAT depots also contained regions of normal up to giant (> 200 µm diameter) adipocytes next to smaller adipocytes (approx. 20 µm).
Conclusion: Knockout of Pten in osteoprogenitor cells leads to alterations in adipose tissue composition and loss of adipose tissue, which is potentially due to increased lipolysis. A downregulation of Pten in osteoprogenitor cells leads to a selective upregulation in WAT indicating a Pten regulation loop between different body compartments.
15 Sep 2022 - 17 Sep 2022