Regional decrease of subcutaneous adipose tissue in patients with type 2 familial partial lipodystrophy is associated...

Area of Science:

• Endocrinology
• Molecular Biology
• Adipose Tissue Biology

Background:

• Familial partial lipodystrophy of the Dunnigan type (FPLD2) is characterized by a loss of subcutaneous adipose tissue (SAT).
• Thyroid hormones (TH) are crucial for adipogenesis, influencing adipose tissue function.
• Investigating TH transport and metabolism in FPLD2 is essential to understand disease mechanisms.

Purpose of the Study:

• To examine gene expression of the TH transporter monocarboxylate transporter 8 (MCT8) and iodothyronine deiodinases (DIOs) in SAT from FPLD2 patients.
• To assess TH nuclear receptor expression and DIO enzyme activities in FPLD2 SAT.
• To determine if altered TH bioavailability and action contribute to FPLD2 pathophysiology.

Main Methods:

• Studied seven FPLD2 subjects and ten healthy controls, obtaining SAT biopsies from abdominal and thigh regions.
• Quantified mRNA expression of MCT8, DIO2, DIO3, THRA1, THRB1, and RXRG using real-time PCR.
• Measured DIO1 and DIO2 enzyme activities and serum TH levels.

Main Results:

• FPLD2 subjects exhibited lower MCT8 mRNA expression in thigh SAT compared to abdominal SAT and controls.
• Increased DIO2 expression and activity were observed in the thigh SAT of FPLD2 subjects compared to abdominal SAT and controls.
• These findings suggest regional differences in TH metabolism within FPLD2 adipose tissue.

Conclusions:

• Thigh SAT in FPLD2 patients shows reduced MCT8 expression and elevated DIO2 expression and activity.
• These alterations indicate potential local dysregulation of thyroid hormone metabolism in lipoatrophic areas.
• DIO2 activity in SAT plays a role in regulating TH metabolism and action in human white adipose tissue.