Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease

Area of Science:

• Metabolic research
• Neurodegenerative disease research
• Adipose tissue biology

Background:

• Metabolic dysregulation is implicated in Huntington's disease (HD) pathogenesis and progression.
• Weight loss is a hallmark of the R6/2 mouse model of HD, typically appearing in later disease stages.

Purpose of the Study:

• To investigate molecular and functional alterations in white adipose tissue (WAT) during weight loss in R6/2 mice.
• To examine the impact of leptin deficiency and early obesity on HD progression in R6/2 mice.

Main Methods:

• Analysis of gonadal and inguinal WAT depot weights and adipocyte size distribution at 12 weeks in R6/2 mice.
• Assessment of adipocyte response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake.
• Comparison between R6/2 mice and wildtype (WT) controls, including leptin-deficient models.

Main Results:

• At 12 weeks, R6/2 mice showed comparable WAT depot weights and adipocyte function to WT mice.
• Leptin-deficient R6/2 mice displayed distinct WAT phenotypes compared to leptin-deficient WT mice.
• Sex-specific adipocyte size changes were observed: smaller adipocytes in females and larger adipocytes in males, with varying body weight impacts.

Conclusions:

• Early, sex-specific alterations in adipocyte size distribution occur in the WAT of R6/2 mice.
• These changes are also evident in leptin-deficient R6/2 mice, highlighting the role of leptin signaling.