Expression of the phosphoenolpyruvate carboxykinase gene in 3T3-F442A adipose cells: opposite effects of dexamethasone and isoprenaline on transcription

Franckhauser, Sylvie; Antras-Ferry, Jocelyne; Robin, Pierre; Robin, D.; Granner, Daryl K.; Forest, Claude

doi:10.1042/bj3050065

Cited by 40 publications

(48 citation statements)

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“…3T3-F442A and 3T3-L1 cells were cultured and differentiated as described (19,20), respectively. 89CRIP cells stably transfected with pLLZ (89CRIR͞nls-lacZ) (21) were from Nicolas Ferry (Rennes, France).…”

Section: Methodsmentioning

confidence: 99%

Obese gene expression at in vivo levels by fat pads derived from s.c. implanted 3T3-F442A preadipocytes

Mandrup

Loftus

MacDougald

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

137

132

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ABSTRACT3T3-F442A preadipocytes implanted s.c. into athymic mice develop into fat pads that are indistinguishable from normal adipose tissue. Implanted preadipocytes harboring a ␤-galactosidase transgene gave rise to fat pads in which almost all adipocytes expressed ␤-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 differentiated into adipocytes in cell culture, express the obese gene at an unexpectedly low level, i.e., <1% the level in adipose 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 findings indicate that a factor(s) or condition, present in the tissue 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, transfected into 3T3-F442A preadipocytes, can be tested in an in vivo context during and after development of these cells into adipose tissue. Furthermore, the effect of transgenes on the adipogenic development of the implanted preadipocytes can be assessed. Thus, this approach offers a faster and less costly alternative to the transgenic mouse method for assessing adipose gene function.

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Section: Methodsmentioning

confidence: 99%

Obese gene expression at in vivo levels by fat pads derived from s.c. implanted 3T3-F442A preadipocytes

Mandrup

Loftus

MacDougald

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

137

132

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“…Transgenic overexpression of PEPCK specifically in adipose tissue leads to increased adiposity based on enhanced re-esterification of free fatty acids within this tissue [185], the effect of which is further aggravated by feeding the animals a high fat diet [186]. In contrast to the liver, GR negatively regulates PEPCK gene expression in adipocytes by interfering with the activity of the pro-glycerogenic transcription factor CCAAT/enhancer binding protein (C/EBP) [187,188] and the pro-glycerogenic actions of PPARγ and α ligands, thiazolidinediones and fibrates, respectively [189]. GCs, thereby, essentially inhibit adipose fat storage and reduce adipose tissue size, which is consistent with the reduced adipose size in animals bearing an inhibitory mutation within the PEPCK promoter region [190].…”

Section: Lipolytic Functions Of Gcsmentioning

confidence: 99%

Glucocorticoids, metabolism and metabolic diseases

Vegiopoulos

Herzig

2007

Molecular and Cellular Endocrinology

440

370

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Since the discovery of the beneficial effects of adrenocortical extracts for treating adrenal insufficiency more than 80 years ago, glucocorticoids (GC) and their cognate, intracellular receptor, the glucocorticoid receptor (GR) have been characterized as critical components of the delicate hormonal control system that determines energy homeostasis in mammals.Whereas physiological levels of GCs are required for proper metabolic control, excessive GC action has been tied to a variety of pandemic metabolic diseases, such as type II diabetes and obesity. Highlighted by its importance for human health, the investigation of molecular mechanisms of GC/GR action has become a major focus in biomedical research. In particular, the understanding of tissue-specific functions of the GC-GR pathway has been proven to be of substantial value for the identification of novel therapeutic options in the treatment of severe metabolic disorders. Therefore, this review focuses on the role of the GC-GR axis for metabolic homeostasis and dysregulation, emphasizing tissue-specific functions of GCs in the control of energy metabolism.

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“…In adipose tissue, glyceroneogenesis controlled by Pck1 contributes to the regulation of FFA release to the blood. Support for Pck1 regulation of glyceroneogenesis contributing to the development of disease was shown by Franckhauser et al They over-expressed of Pck1 in WAT through a transgene specific for adipose tissue and found increased FFA re-esterification in adipose tissue led to obesity without insulin resistance (Franckhauser, Antras-Ferry et al 1995;Franckhauser, Munoz et al 2002). The increased glyceroneogenesis reduced the availability of FFA to the muscle and thus prevented impaired glucose tolerance.…”

Section: Triglyceride/fatty Acid Cycle and Glyceroneogenesismentioning

confidence: 93%