Lipoatrophy induced by subcutaneous insulin infusion: ultrastructural analysis and gene expression profiling

Area of Science:

• Endocrinology
• Metabolic Research
• Adipose Tissue Biology

Background:

• Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication linked to insulin therapy.
• Understanding the ultrastructural and molecular basis of LA is crucial for managing insulin-treated patients.

Observation:

• LA lesions in type 1 diabetes patients showed smaller, unilocular adipocytes with lipofuscin, "slimmed cells" lacking lipid droplets, and numerous perivascular preadipocytes.
• No inflammatory cells were detected in the affected SAT.
• SAT within LA areas exhibited significantly reduced leptin and increased AEBP1, a preadipocyte marker.

Findings:

• The reduction in SAT volume in LA is attributed to decreased adipocyte lipid content and size, not cell death.
• The study identified "slimmed cells" and increased preadipocytes, suggesting a localized response to chronic high insulin exposure.
• Molecular analysis revealed leptin downregulation and AEBP1 upregulation in affected SAT.

Implications:

• LA pathogenesis likely involves adipocyte insulin resistance leading to increased lipolysis, rather than immune-mediated damage.
• Preadipocyte recruitment contributes to LA regression, but adipose tissue regeneration requires cessation of local insulin administration.
• Findings offer insights into managing localized fat atrophy in patients undergoing insulin therapy.