ORCID Profile
0000-0002-1616-4179
Current Organisation
Nottingham Trent University
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Publisher: American Society for Clinical Investigation
Date: 09-07-2018
DOI: 10.1172/JCI120115
Publisher: American Physiological Society
Date: 15-04-2014
DOI: 10.1152/AJPENDO.00473.2013
Abstract: Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a “brite” transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with “browning,” as these represent novel targets for understanding this process. For ex le, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.
Publisher: The Endocrine Society
Date: 15-12-2010
DOI: 10.1210/EN.2010-0899
Abstract: Differentiation of human endometrial stromal cells into specialized decidual cells is critical for embryo implantation and survival of the conceptus. Initiation of this differentiation process is strictly dependent on elevated cAMP levels, but the signal intermediates that control the expression of decidual marker genes, such as prolactin (PRL) and IGFBP1, remain poorly characterized. Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. Time-course analysis demonstrated that cAMP enhances endogenous reactive oxygen species production, apparent after 12 h of stimulation, which coincides with a dramatic increase in decidual PRL and IGFBP1 expression. Knockdown of the Rho GTPase RAC1, which disables activation of the NADPH oxidase homologs NADPH oxidase (NOX)-1, NOX-2, and NOX-3, had no effect on PRL or IGFBP1 expression. In contrast, silencing of NOX-4, or its cofactor p22PHOX, inhibited the expression of both decidual markers. Finally, we show that the NOX-4 22PHOX complex regulates the DNA-binding activity of CCAAT/enhancer binding protein-β, a key regulator of human endometrial stromal cell differentiation. Thus, NOX-4 activation and reactive oxygen species signaling play an integral role in initiating the endometrial decidual response in preparation of pregnancy.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1194/JLR.M049551
Publisher: EMBO
Date: 17-01-2018
Publisher: EMBO
Date: 09-01-2020
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mark Christian.