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Experiment

Metabolic Cage Study in HFD-fed Hig2 KO Mice
Summary Data Summary
Investigator Czech, Michael
Description We have shown that Hig2 is a lipid droplet protein and want to investigate its
role in adipocytes. The knockouts have reduced adipose tissue weight and
improved glucose tolerance on HFD.

The liver is a major site of glucose, fatty acid, and triglyceride (TG)
synthesis and serves as a major regulator of whole body nutrient homeostasis.
Chronic exposure of humans or rodents to high-calorie diets promotes
non-alcoholic fatty liver disease, characterized by neutral lipid accumulation
in lipid droplets (LD) of hepatocytes. Here we show that the LD protein
hypoxia-inducible gene 2 (Hig2/Hilpda) functions to enhance lipid accumulation
in hepatocytes by attenuating TG hydrolysis. Hig2 expression increased in livers
of mice on a high-fat diet and during fasting, two states associated with
enhanced hepatic TG content. Hig2 expressed in primary mouse hepatocytes
localized to LDs and promoted LD TG deposition in the presence of oleate.
Conversely, tamoxifen-inducible Hig2 deletion reduced both TG content and LD
size in primary hepatocytes from mice harboring floxed alleles of Hig2 and a
cre/ERT2 transgene controlled by the ubiquitin C promoter. Hepatic TG was also
decreased by liver-specific deletion of Hig2 in mice with floxed Hig2 expressing
cre controlled by the albumin promoter. Importantly, we demonstrate that
Hig2-deficient hepatocytes exhibit increased TG lipolysis, TG turnover, and
fatty acid oxidation as compared with controls. Interestingly, mice with
liver-specific Hig2 deletion also display improved glucose tolerance. Taken
together, these data indicate that Hig2 plays a major role in promoting lipid
sequestration within LDs in mouse hepatocytes through a mechanism that impairs
TG degradation.

Applicable research area(s): Obesity, Metabolism
Status Completed
Public Release 4/24/2018
Animal Age Measured In: week(s) post-natal (w)
Flags has-data-flagSame StrainMetadataExperiment Description
Data Analysis
TypeCount
Animals5
Experimental Conditions2
Catalog Items3
Curation Info (# flags)3
Phenotype Assays9
Phenotype Measurements45
Histology Images0
Publications0


Animals

Strain NameCommon NameFemalesMalesUnknown
C57BL/6
0
3
0
Hig2 KO
0
2
0


Experimental Factors
 Name / AbbreviationDescription

Experimental Factor: Experimental Group

 Control
This animal belongs to the control group for the experiment.
 Experiment
This animal belongs to experimental group that is homozygous for gene manipulations.

Experimental Factor: Mouse Diet

 Research Diets - D12492i
Irradiated form of D12492, Rodent Diet with 60% kcal% fat.



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