Stress-responsive HILPDA is necessary for thermoregulation during fasting.

Hypoxia-inducible lipid droplet-associated protein (HILPDA) has been shown to localize to lipid droplets in nutrient-responsive cell types such as hepatocytes and adipocytes. However, its role in the control of whole-body homeostasis is not known. We sought to measure cell-intrinsic and systemic stress responses in a mouse strain harboring whole-body Hilpda deficiency. We generated a genetically engineered mouse model of whole-body HILPDA deficiency by replacing the coding Hilpda exon with luciferase. We subjected the knockout animals to environmental stresses and measured whole-animal metabolic and behavioral parameters. Brown adipocyte precursors were isolated and differentiated in vitro to quantify the impact of HILPDA ablation in lipid storage and mobilization in these cells. HILPDA-knockout animals are viable and fertile, but show reduced ambulatory activity and oxygen consumption at regular housing conditions. Acclimatization at thermoneutral conditions abolished the phenotypic differences observed at 22°C. When fasted, HILPDA KO mice are unable to maintain body temperature and become hypothermic at 22°C, without apparent abnormalities in blood chemistry parameters or tissue triglyceride content. HILPDA expression was upregulated during adipocyte differentiation and activation in vitro; however, it was not required for lipid droplet formation in brown adipocytes. We conclude that HILPDA is necessary for efficient fuel utilization suggesting a homeostatic role for Hilpda in sub-optimal environments. © 2017 Society for Endocrinology.

Citation

Matthew J VandeKopple, Jinghai Wu, Lisa A Baer, Naresh C Bal, Santosh K Maurya, Anuradha Kalyanasundaram, Muthu Periasamy, Kristin I Stanford, Amato J Giaccia, Nicholas C Denko, Ioanna Papandreou. Stress-responsive HILPDA is necessary for thermoregulation during fasting. The Journal of endocrinology. 2017 Oct;235(1):27-38

Mesh Tags

Substances

PMID: 28739822

search → result