Stress-responsive HILPDA is necessary for thermoregulation during fasting

Area of Science:

• Metabolic research
• Physiology
• Molecular biology

Background:

• Hypoxia-inducible lipid droplet-associated protein (HILPDA) is found in lipid droplets of cells like hepatocytes and adipocytes.
• The function of HILPDA in whole-body homeostasis and stress response remains unclear.

Purpose of the Study:

• To investigate the role of HILPDA in whole-body homeostasis and stress responses.
• To characterize the metabolic and behavioral phenotypes of mice lacking HILPDA.

Main Methods:

• Generated whole-body HILPDA-knockout mice by replacing the coding exon with luciferase.
• Assessed metabolic and behavioral parameters under various environmental conditions.
• Isolated and differentiated brown adipocyte precursors in vitro to study lipid metabolism.

Main Results:

• HILPDA-knockout mice exhibited reduced activity and oxygen consumption at standard temperatures (22°C).
• Phenotypic differences disappeared at thermoneutral conditions.
• Knockout mice became hypothermic when fasted at 22°C, despite normal blood chemistry and triglyceride levels.
• HILPDA expression increased during adipocyte differentiation but was not essential for lipid droplet formation in brown adipocytes.

Conclusions:

• HILPDA is essential for efficient fuel utilization and maintaining body temperature in suboptimal environments.
• HILPDA plays a critical homeostatic role, particularly under conditions of environmental stress and fasting.