Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity

Cody McGrath, Sarah E. Little-Letsinger, Jeyantt Srinivas Sankaran, Buer Sen, Zhihui Xie, Martin A. Styner, Xiaopeng Zong, Weiqin Chen, Janet Rubin, Eric L. Klett, Rosalind A. Coleman, Maya Styner

Research output: Contribution to journalArticlepeer-review

Abstract

Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation’s most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via μCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p<0.001) but not in KO. Notably, exercise increased trabecular BV/TV in both (+31%, KO-E vs KO, p=0.004; +14%, WT-E vs WT, p=0.006). The presence and distribution of BMAT in SEIPIN KO, though lower than WT, is unexpected and points to a uniqueness of this depot. That trabecular bone increases were achievable in both KO and WT, despite a difference in BMAT quantity/distribution, points to potential metabolic flexibility during exercise-induced skeletal anabolism.

Original languageEnglish (US)
Article number782194
JournalFrontiers in Endocrinology
Volume12
DOIs
StatePublished - Jan 25 2022
Externally publishedYes

Keywords

  • anabolism
  • bone
  • bone marrow adipose tissue (BMAT)
  • BSCL2
  • congenital lipodystrophy
  • endocrinology and metabolism
  • exercise
  • SEIPIN

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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