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Ormonda . Macdougald

Bio: Ormonda . Macdougald is an academic researcher. The author has contributed to research in topics: Adipogenesis & Adipose tissue. The author has an hindex of 1, co-authored 1 publications receiving 6 citations.

Papers
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01 Jan 1997
TL;DR: These findings indicate that adipose-specific promoter-reporter constructs, transfected into 3T3-F442A preadipocytes, can be tested in an in vivo context during and after development of these cells into adipose tissue, and offer a faster and less costly alternative to the transgenic mouse method for assessing adipose gene function.
Abstract: T3-F442Apreadipocytesimplanteds.c.into athymic mice develop into fat pads that are indistinguishable fromnormaladiposetissue.Implantedpreadipocytesharbor- ing a b-galactosidase transgene gave rise to fat pads in which almost all adipocytes expressed b-galactosidase. This finding proved that the implanted 3T3-F442A preadipocytes, rather than endogenous preadipose cells, gave rise to the newly developed ''adipose tissue.'' 3T3-F442A preadipocytes, when differentiatedintoadipocytesincellculture,expresstheobese geneatanunexpectedlylowlevel,i.e.,<1%thelevelinadipose tissue. However, adipose tissue derived from s.c. implanted 3T3-F442A preadipocytes expressed leptin mRNA at a level comparable to that in epididymal adipose tissue. These find- ingsindicatethatafactor(s)orcondition,presentinthetissue context and necessary for maximal obese gene expression, is lacking in cell culture. Furthermore, adipocytes derived from the implanted cells were hormonally responsive in that leptin mRNA levels were up-regulated 3- to 8-fold by glucocorticoid injection into the host animal. Thus, these findings indicate that adipose-specific promoter-reporter constructs, trans- fected into 3T3-F442A preadipocytes, can be tested in an in vivocontext during and after development of these cells into adipose tissue. Furthermore, the effect of transgenes on the adipogenicdevelopmentoftheimplantedpreadipocytescanbe assessed. Thus, this approach offers a faster and less costly alternative to the transgenic mouse method for assessing adipose gene function.

6 citations


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01 Jan 2010
TL;DR: A critical role is established for SENP2 in the regulation of adipogenesis by desumoylation and stabilization of C/EBPβ and in turn by promoting the expression of its downstream effectors, such as PPARγ and C/ EBPα.
Abstract: Here, we demonstrate that SENP2, a desumoylating enzyme, plays a critical role in the control of adipogenesis. SENP2 expression was markedly increased upon the induction of adipocyte differentiation, and this increase was dependent on protein kinase A activation. Remarkably, knockdown of SENP2 led to a dramatic attenuation of adipogenesis with a marked decrease in PPARγ and C/EBPα mRNA levels. Knockdown of SENP2 also caused a marked reduction in the level of C/EBPβ protein but not in that of C/EBPβ mRNA. Interestingly, sumoylation of C/EBPβ dramatically increased its ubiquitination and destabilization, and this increase could be reversed by SENP2. In addition, overexpression of C/EBPβ could overcome the inhibitory effect of SENP2 knockdown on adipogenesis. Furthermore, SENP2 was absolutely required for adipogenesis of preadipocytes implanted into mice. These results establish a critical role for SENP2 in the regulation of adipogenesis by desumoylation and stabilization of C/EBPβ and in turn by promoting the expression of its downstream effectors, such as PPARγ and C/EBPα.

11 citations

Dissertation
01 Jan 2015
TL;DR: The results suggest that the adipose tissue remodelling process in obesity could play a central role in ER stress induction in adipocytes, and indicate for the first time that glucose starvation and hypoxia, two markers of adipose tissues remodelling in obesity, represent physiological triggers of ER stress in in vitro differentiated adipocytes.
Abstract: Obesity is the most common nutritional disorder in the developed world and represents a major risk factor for associated diseases like type 2 diabetes mellitus, cardiovascular diseases and hypertension. The condition affects the whole body homeostasis but mainly the adipose tissue and is characterised by low grade inflammation, insulin resistance and hyperlipidemia. In adipocytes, it has been associated with endoplasmic reticulum stress (ER stress) induction and activation of the unfolded protein response (UPR). ER stress has been shown to play a central role in the molecular events leading to inflammation and insulin resistance in obese adipocytes, but the physiological triggers of ER stress are still unknown. The aim of my thesis was to investigate the role of obesity-related factors such as high concentrations of saturated fatty acids, cholesterol, proinflammatory cytokines or tissue remodelling-induced hypoxia and glucose starvation in ER stress induction My results indicate for the first time that glucose starvation and hypoxia, two markers of adipose tissue remodelling in obesity, represent physiological triggers of ER stress in in vitro differentiated 3T3-F442A and 3T3-L1 adipocytes. High concentrations of saturated fatty acid palmitic acid, cholesterol or proinflammatory cytokines (TNFα, IL-6 and IL-1β), although shown to be potent inducers in other cell lines, do not induce ER stress in my model of in vitro differentiated adipocytes. In conclusion, my results suggest that the adipose tissue remodelling process in obesity could play a central role in ER stress induction in adipocytes.

4 citations

15 Jan 2014
TL;DR: The data suggest that preadipocyte-secreted HGF is an important regulator of neovascularization in developing fat pads, and c-MET knockdown fat pads developed a robust vasculature, andPreadipocytes differentiated to mature adipocytes.
Abstract: In this study, we used lentiviral-delivered shRNA to generate a clonal line of 3T3-F442A preadipocytes with stable silencing of hepatocyte growth factor (HGF) expression and examined the long-term consequence of this modification on fat pad development. HGF mRNA expression was reduced 94%, and HGF secretion 79% (P < 0.01), compared with preadipocytes treated with nontargeting shRNA. Fat pads derived from HGF knockdown preadipocytes were significantly smaller (P < 0.01) than control pads beginning at 3 days postinjection (0.022 ± 0.003 vs. 0.037 ± 0.004 g), and further decreased in size at day 7 (0.015 ± 0.004 vs. 0.037 ± 0.003 g) and day 14 (0.008 ± 0.002 vs. 0.045 ± 0.007 g). Expression of the endothelial cell genes TIE1 and PECAM1 increased over time in control fat pads (1.6 ± 0.4 vs. 11.4 ± 1.7 relative units at day 3 and 14, respectively; P < 0.05) but not in HGF knockdown fat pads (1.1 ± 0.5 vs. 5.9 ± 2.2 relative units at day 3 and 14). Contiguous vascular structures were observed in control fat pads but were much less developed in HGF knockdown fat pads. Differentiation of preadipocytes to mature adipocytes was significantly attenuated in HGF knockdown fat pads. Fat pads derived from preadipocytes with knockdown of the HGF receptor c-MET were smaller than control pads at day 3 postinjection (0.034 ± 0.002 vs. 0.049 ± 0.004 g; P < 0.05), and remained the same size through day 14. c-MET knockdown fat pads developed a robust vasculature, and preadipocytes differentiated to mature adipocytes. Overall these data suggest that preadipocyte-secreted HGF is an important regulator of neovascularization in developing fat pads.

1 citations

01 Jan 2007
TL;DR: The final author version and the galley proof are versions of the publication after peer review that features the final layout of the paper including the volume, issue and page numbers.
Abstract: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers.

1 citations