Balb/c mice are protected from glucose and acute cold intolerance

Area of Science:

• Metabolic disorders
• Thermogenesis regulation
• Adipose tissue function

Background:

• Brown adipose tissue (BAT) is a key target for metabolic disorder treatments.
• Genetic and environmental factors influence BAT function and thermogenesis.
• Investigating gene-environment interactions can reveal novel regulatory mechanisms.

Purpose of the Study:

• To compare the BAT function and metabolic response of three distinct mouse strains under cold exposure and high-fat diet.
• To identify mechanisms underlying superior cold and glucose tolerance in specific mouse strains.
• To explore the role of PM20D1 in thermogenesis and metabolic regulation.

Main Methods:

• Comparative analysis of Balb/c, C57BL/6, and Swiss mice strains.
• Assessment of brown adipose tissue (BAT) function, including oxygen consumption and uncoupling protein 1 (UCP1) expression.
• Gene expression analysis of PM20D1 in BAT.
• In vivo immunoneutralization of PM20D1 and in silico knockout studies.

Main Results:

• Balb/c mice exhibited superior glucose tolerance and cold tolerance compared to other strains.
• Higher BAT oxygen consumption in Balb/c mice, independent of UCP1.
• Elevated PM20D1 gene expression in Balb/c mouse BAT.
• PM20D1 inhibition worsened glucose levels and cold tolerance in Balb/c mice.

Conclusions:

• Balb/c mice possess inherent protection against glucose intolerance and cold stress, irrespective of diet.
• PM20D1 plays a significant role in this protection through an uncoupling protein 1-independent pathway.
• PM20D1 emerges as a potential therapeutic target for metabolic disorders.