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Publication
Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and
diet-induced insulin resistance.
Authors DiStefano MT, Roth Flach RJ, Senol-Cosar O, Danai LV, Virbasius JV, Nicoloro SM,
Straubhaar J, Dagdeviren S, Wabitsch M, Gupta OT, Kim JK, Czech MP
Submitted By Submitted Externally on 4/12/2017
Status Published
Journal Molecular metabolism
Year 2016
Date Published 12/1/2016
Volume : Pages 5 : 1149 - 1161
PubMed Reference 27900258
Abstract Adipose tissue relies on lipid droplet (LD) proteins in its role as a
lipid-storing endocrine organ that controls whole body metabolism.
Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein
in hepatocytes that promotes hepatic lipid storage, but its role in the
adipocyte had not been investigated. Here we tested the hypothesis that Hig2
localization to LDs in adipocytes promotes adipose tissue lipid deposition and
systemic glucose homeostasis., White and brown adipocyte-deficient
(Hig2(fl/fl) × Adiponection cre+) and selective brown/beige adipocyte-deficient
(Hig2(fl/fl) × Ucp1 cre+) mice were generated to investigate the role of Hig2 in
adipose depots. Additionally, we used multiple housing temperatures to
investigate the role of active brown/beige adipocytes in this process., Hig2
localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with
adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced
visceral adipose tissue weight and increased glucose tolerance. This metabolic
effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency
since Hig2(fl/fl) × Ucp1 cre+ mice displayed the same phenotype. Furthermore,
when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in
which non-shivering thermogenesis is deactivated, these improvements were
abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient
animals displayed no detectable changes in adipocyte lipolysis or energy
expenditure, suggesting that Hig2 may not mediate these metabolic effects by
restraining lipolysis in adipocytes., We conclude that Hig2 localizes to LDs in
adipocytes, promoting adipose tissue lipid deposition and that its selective
deficiency in active brown/beige adipose tissue mediates improved glucose
tolerance at 23 °C. Reversal of this phenotype at thermoneutrality in the
absence of detectable changes in energy expenditure, adipose mass, or liver
triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or
neuroendocrine pathway emanating from brown/beige fat cells.




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