Increased susceptibility to OVX-associated metabolic dysfunction in UCP1-null mice

Area of Science:

• Metabolic Health
• Endocrinology
• Brown Adipose Tissue Biology

Background:

• Premenopausal females exhibit protection against adipose tissue inflammation and insulin resistance, which diminishes with ovarian hormone loss (menopause).
• Females may possess a greater brown adipose tissue (BAT) thermogenic capacity, and BAT mass inversely correlates with insulin resistance.

Purpose of the Study:

• To investigate the hypothesis that increased uncoupling protein 1 (UCP1) expression contributes to females' superior metabolic health.
• To determine if UCP1 buffers ovariectomy (OVX)-induced metabolic dysfunction, given UCP1's transient increase in BAT post-OVX.

Main Methods:

• Female UCP1-knockout (KO) and wild-type (WT) mice underwent OVX or sham surgery.
• Metabolic parameters including body weight, adiposity, food intake, energy expenditure, physical activity, and insulin resistance (HOMA-IR, ADIPO-IR, glucose tolerance tests) were assessed over 14 weeks.
• Adipose tissue phenotype was analyzed via histology, gene, and protein expression. Statistical analysis used two-way ANOVA.

Main Results:

• UCP1 KO mice showed a more adverse metabolic response to OVX compared to WT mice.
• While OVX-induced weight gain was similar between genotypes, OVX-induced insulin resistance was significantly exacerbated in UCP1 KO mice (P < 0.05).

Conclusions:

• UCP1 plays a protective role against metabolic dysfunction associated with the loss of ovarian hormones.
• These findings suggest UCP1 is a potential therapeutic target for preventing and treating metabolic dysfunction after menopause.