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

• Published in: Frontiers in endocrinology (Lausanne) 2022-01, Vol.12, p.782194-782194
• Main Authors: McGrath, Cody, Little-Letsinger, Sarah E, Sankaran, Jeyantt Srinivas, Sen, Buer, Xie, Zhihui, Styner, Martin A, Zong, Xiaopeng, Chen, Weiqin, Rubin, Janet, Klett, Eric L, Coleman, Rosalind A, Styner, Maya
• Format: Article
• Language: English
• Subjects: Adipose Tissue - diagnostic imaging; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Body Weight; bone; Bone Marrow - diagnostic imaging; Bone Marrow - metabolism; Bone Marrow - pathology; BSCL2; Cancellous Bone - diagnostic imaging; Cancellous Bone - metabolism; congenital lipodystrophy; Diaphyses - diagnostic imaging; Disease Models, Animal; Endocrinology; endocrinology and metabolism; Epididymis - metabolism; Epididymis - pathology; exercise; Femur - diagnostic imaging; Femur - metabolism; GTP-Binding Protein gamma Subunits - genetics; Lipodystrophy - diagnostic imaging; Lipodystrophy - genetics; Lipodystrophy - metabolism; Lipodystrophy - pathology; Male; Mice; Mice, Knockout; Organ Size; Perilipin-1 - genetics; Physical Conditioning, Animal; SEIPIN; X-Ray Microtomography
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2021.782194

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