Dataset Information

Stress-responsive HILPDA is necessary for thermoregulation during fasting.

ABSTRACT: 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.

SUBMITTER: VandeKopple MJ

PROVIDER: S-EPMC5567683 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Stress-responsive HILPDA is necessary for thermoregulation during fasting.

VandeKopple Matthew J MJ Wu Jinghai J Baer Lisa A LA Bal Naresh C NC Maurya Santosh K SK Kalyanasundaram Anuradha A Periasamy Muthu M Stanford Kristin I KI Giaccia Amato J AJ Denko Nicholas C NC Papandreou Ioanna I

The Journal of endocrinology 20170724 1

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 <i>Hilpda</i> exon wit ...[more]

PMID: 28739822

Similar Datasets

Project description:Management of large herbivores depends on providing habitats for forage supply and refuge from risks of temperature, predation and disease. Moose (Alces alces) accumulate body energy and nutrient stores during summer, while reducing the impact of warm temperatures through physiological and behavioural thermoregulation. Building on the animal indicator concept, we used rumen temperature sensors and GPS collars on captive moose (n = 6) kept in large natural enclosures to evaluate how behaviour and habitat selection influence the rate of change in rumen temperature during the growing season on the Kenai Peninsula, Alaska, USA. We compared movement and habitat selection of individual females during tolerance days (daily amplitude in rumen temperature was ≥1.2°C in 24 h) with those of control days (daily amplitude in rumen temperature was < 1.2°C) before and after the tolerance day. Moose moved more during tolerance days (172 m • h-1; 95% confidence intervals (CI) = 149-191 m • h-1) than on control days (151 m • h-1; 95% CI = 128-173 m • h-1). The rate of change in rumen temperature (°C • h-1) declined with low to moderate movement rates that were probably associated with foraging in all habitats. Movement only increased the rate of change in rumen temperature at high activity (~ > 500 m • h-1). Additionally, the relationship between rate of change in rumen temperature and movement rate was different during tolerance and control days in open meadow and wetland habitats. In all habitats except wetlands, the rate of change in rumen temperature increased while resting, which probably is a result of diet-induced thermogenesis. Our study demonstrates that the behavioural choices of moose on the landscape are associated with the rate of change in rumen temperature and their ability to thermoregulate. Wildlife managers must consider high-value habitats where wildlife can employ both behavioural and physiological mechanisms to tolerate warm ambient conditions in a landscape of forage, predators and pests.

Project description:BACKGROUND AND OBJECTIVES:Marathon runners develop transient AKI with urine sediments and injury biomarkers suggesting nephron damage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:To investigate the etiology, we examined volume and thermoregulatory responses as possible mechanisms in runners' AKI using a prospective cohort of runners in the 2017 Hartford Marathon. Vitals, blood, and urine samples were collected in 23 runners 1 day premarathon and immediately and 1 day postmarathon. We measured copeptin at each time point. Continuous core body temperature, sweat sodium, and volume were assessed during the race. The primary outcome of interest was AKI, defined by AKIN criteria. RESULTS:Runners ranged from 22 to 63 years old; 43% were men. Runners lost a median (range) of 2.34 (0.50-7.21) g of sodium and 2.47 (0.36-6.81) L of volume via sweat. After accounting for intake, they had a net negative sodium and volume balance at the end of the race. The majority of runners had increases in core body temperature to 38.4 (35.8-41)°C during the race from their baseline. Fifty-five percent of runners developed AKI, yet 74% had positive urine microscopy for acute tubular injury. Runners with more running experience and increased participation in prior marathons developed a rise in creatinine as compared with those with lesser experience. Sweat sodium losses were higher in runners with AKI versus non-AKI (median, 3.41 [interquartile range (IQR), 1.7-4.8] versus median, 1.4 [IQR, 0.97-2.8] g; P=0.06, respectively). Sweat volume losses were higher in runners with AKI versus non-AKI (median, 3.89 [IQR, 1.49-5.09] versus median, 1.66 [IQR, 0.72-2.84] L; P=0.03, respectively). Copeptin was significantly higher in runners with AKI versus those without (median, 79.9 [IQR, 25.2-104.4] versus median, 11.3 [IQR, 6.6-43.7]; P=0.02, respectively). Estimated temperature was not significantly different. CONCLUSIONS:All runners experienced a substantial rise in copeptin and body temperature along with salt and water loss due to sweating. Sodium and volume loss via sweat as well as plasma copeptin concentrations were associated with AKI in runners. PODCAST:This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_08_13_CJASNPodcast_19_09_.mp3.

Dataset Information

Stress-responsive HILPDA is necessary for thermoregulation during fasting.

Publications

Stress-responsive HILPDA is necessary for thermoregulation during fasting.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets