GADD45γ regulates the thermogenic capacity of brown adipose tissue

Gantner, Marin L.; Hazen, Bethany C.; Conkright, Juliana J.; Kralli, Anastasia

doi:10.1073/pnas.1406638111

Cited by 44 publications

(46 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, Gadd45γ has been identified as a cold-inducible activator of ERRγ in BAT (Gantner et al, 2014), suggesting the model that baseline expression of ERRγ promotes depot resilience in the TN state effectively priming BAT for thermogenesis with Gadd45γ amplifying the response upon acute cold exposure. These results, combined with the finding that ERRγ maintains a highly oxidative state in muscle in the absence of exercise (Narkar et al, 2011), implicate ERRγ in controlling metabolism under innate rather than adaptive conditions.…”

Section: Discussionmentioning

confidence: 99%

ERRγ Preserves Brown Fat Innate Thermogenic Activity

et al. 2018

View full text Add to dashboard Cite

SUMMARY Brown adipose tissue (BAT) adaptively transfers energy from glucose and fat into heat by inducing a gene network that uncouples mitochondrial electron transport. However, the innate transcription factors that enable the rapid adaptive response of BAT are unclear. Here, we identify estrogen-related receptor gamma (ERRγ) as a critical factor for maintaining BAT identity. ERRγ is selectively expressed in BAT versus WAT, in which, in the absence of PGC1α, it drives a signature transcriptional network of thermogenic and oxidative genes in the basal (i.e., thermoneutral) state. Mice lacking ERRγ in adipose tissue (ERRγKO mice) display marked downregulation of BAT-selective genes that leads to a pronounced whitening of BAT. Consistent with the transcriptional changes, the thermogenic capacity of ERRγKO mice is severely blunted, such that they fail to survive an acute cold challenge. These findings reveal a role for ERRγ as a critical thermoneutral maintenance factor required to prime BAT for thermogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

ERRγ Preserves Brown Fat Innate Thermogenic Activity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Cholesterol synthesis genes are weakly suppressed by GVAD compared to the oleic acid pathway, but show a stronger reversal of the Cyp1b1 deletion effects by GVAD. This response signature is shared by Gadd45γ , a major regulator of DNA demethylation and developmental processes (Gierl et al, 2012, Johnen et al, 2013, Kaufmann et al, 2011, Warr et al, 2012), including brown fat regulation (Gantner et al, 2014). …”

Section: Discussionmentioning

confidence: 99%

Cyp1b1 deletion and retinol deficiency coordinately suppress mouse liver lipogenic genes and hepcidin expression during post-natal development

Maguire

Larsen

Foong

et al. 2017

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Cyp1b1 deletion and gestational vitamin A deficiency (GVAD) redirect adult liver gene expression. A matched sufficient pre- and post-natal diet, which has high carbohydrate and normal iron content (LF12), increased inflammatory gene expression markers in adult livers that were suppressed by GVAD and Cyp1b1 deletion. At birth on the LF12 diet, Cyp1b1 deletion and GVAD each suppress liver expression of the iron suppressor, hepcidin (Hepc), while increasing stellate cell activation markers and suppressing post-natal increases in lipogenesis. Hepc was less suppressed in Cyp1b1−/− pups with a standard breeder diet, but was restored by iron supplementation of the LF12 diet. Conclusions The LF12 diet delivered low post-natal iron and attenuated Hepc. Hepc decreases in Cyp1b1−/− and GVAD mice resulted in stellate activation and lipogenesis suppression. Endothelial BMP6, a Hepc stimulant, is a potential coordinator and Cyp1b1 target. These neonatal changes in Cyp1b1−/− mice link to diminished adult obesity and liver inflammation.

show abstract

“…Primers were designed for mouse by us, or were based on studied by others. 24 Primer design was performed using the PrimerExpress software (Applied Biosystems, Foster City, CA), or through the Genescript online tool (https://www.genscript.com/ssl-bin/app/primer). Mitochondrial complexes components were evaluated using the PCR array designed by SABiosciences/Qiagen (Valencia, CA) with a focus on Mitochondrial Energy Metabolism (Catalog # PAMM-008Z).…”

Section: Methodsmentioning

confidence: 99%

Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

et al. 2014

View full text Add to dashboard Cite

Hyperthermia is a potentially lethal side effect of Methamphetamine (Meth) abuse, which involves the participation of peripheral thermogenic sites such as the Brown Adipose Tissue (BAT). In a previous study we found that the anti-oxidant N-acetyl cysteine (NAC) can prevent the high increase in temperature in a mouse model of Meth-hyperthermia. Here, we have further explored the ability of NAC to modulate Meth-induced hyperthermia in correlation with changes in BAT. We found that NAC treatment in controls causes hypothermia, and, when administered prior or upon the onset of Meth-induced hyperthermia, can ameliorate the temperature increase and preserve mitochondrial numbers and integrity, without affecting locomotor activity. This was different from Dantrolene, which decreased motor activity without affecting temperature. The effects of NAC were seen in spite of its inability to recover the decrease of mitochondrial superoxide induced in BAT by Meth. In addition, NAC did not prevent the Meth-induced decrease of BAT glutathione. Treatment with S-adenosyl-L-methionine, which improves glutathione activity, had an effect in ameliorating Meth-induced hyperthermia, but also modulated motor activity. This suggests a role for the remaining glutathione for controlling temperature. However, the mechanism by which NAC operates is independent of glutathione levels in BAT and specific to temperature. Our results show that, in spite of the absence of a clear mechanism of action, NAC is a pharmacological tool to examine the dissociation between Meth-induced hyperthermia and motor activity, and a drug of potential utility in treating the hyperthermia associated with Meth-abuse.

show abstract

GADD45γ regulates the thermogenic capacity of brown adipose tissue

Cited by 44 publications

References 42 publications

ERRγ Preserves Brown Fat Innate Thermogenic Activity

ERRγ Preserves Brown Fat Innate Thermogenic Activity

Cyp1b1 deletion and retinol deficiency coordinately suppress mouse liver lipogenic genes and hepcidin expression during post-natal development

Reactive oxygen species scavenger N-acetyl cysteine reduces methamphetamine-induced hyperthermia without affecting motor activity in mice

Contact Info

Product

Resources

About