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

Area of Science:

• Endocrinology
• Bone Biology
• Metabolic Disorders

Background:

• Lipodystrophy is characterized by a lack of white adipose tissue, often leading to diabetes and steatosis.
• The role of exercise in lipodystrophy, particularly concerning skeletal health, remains uninvestigated.
• SEIBold (SEIPIN) is crucial for lipid droplet formation and adipose tissue development.

Purpose of the Study:

• To investigate the effects of exercise on skeletal health in a mouse model of lipodystrophy with SEIPIN deficiency.
• To examine bone marrow adipose tissue (BMAT) quantity and distribution in SEIPIN-deficient mice.
• To assess exercise's impact on bone parameters and metabolic adaptations in this model.

Main Methods:

• Utilized a global SEIPIN knockout (KO) mouse model and wild-type (WT) littermates.
• Assigned mice to six weeks of voluntary running exercise (E) or no exercise (N).
• Assessed body weight, adipose tissue, liver steatosis (Plin1 expression), bone marrow adiposity (9.4T MRI), and bone structure (μCT).

Main Results:

• SEIPIN KO mice exhibited reduced body weight, absence of epididymal adipose tissue, and significant liver steatosis.
• BMAT was present but lower in KO mice, with notable regional differences in the femur.
• Exercise reduced weight in WT but not KO mice; however, exercise increased trabecular bone volume fraction (BV/TV) in both KO and WT mice.

Conclusions:

• SEIPIN deficiency leads to lipodystrophy, altered BMAT distribution, and preserved bone structure.
• Exercise can induce skeletal benefits (increased trabecular bone) in SEIPIN-deficient mice, despite metabolic differences.
• These findings suggest potential metabolic flexibility during exercise-induced bone anabolism, even in lipodystrophy.