Chemistry: molecular biology and microbiology – Process of mutation – cell fusion – or genetic modification – Introduction of a polynucleotide molecule into or...
Patent
1998-01-05
2000-06-06
Yucel, Remy
Chemistry: molecular biology and microbiology
Process of mutation, cell fusion, or genetic modification
Introduction of a polynucleotide molecule into or...
435366, 435377, 435455, C12N 1587, C12N 508
Patent
active
060717475
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to immortalized cell lines from human adipose tissue, to the process for their preparation and to their applications as a model for studying the physiopathology of the metabolism, especially obesity and diabetes, as tools for the development of drugs for the treatment of pathological conditions associated with metabolic disorders such as obesity and diabetes, and as drugs.
Obesity and diabetes constitute major health problems in the West and important risk factors in early mortality. The factors considered to be responsible for the development of obesity and diabetes are not yet all well known. However, it is now widely acknowledged that thermogenesis defects (for example defects of energy dissipation in the form of heat, with the consequence of lipid accumulation) are involved in the mechanisms of obesity; it is also widely acknowledged that adipose tissue, especially brown adipose tissue, is the principal effector of optional chemical thermogenesis.
Adipose tissue (brown and white) essentially consists of adipocytes (3/4 of the total number of adipose tissue cells). The other cells present in adipose tissue belong especially to precursor cells, also called interstitial cells (lipid-free cells), and comprise particularly adipoblasts (lipid-free mesenchymal cells) and preadipocytes (lipid-free esterase-positive cells).
White adipose tissue (or WAT) is considered to be a different organ from brown adipose tissue (or BAT); these two adipose tissues are distinguished especially by the fact that their precursor cells are different; the presence of uncoupling proteins (or UCP) is specific to BAT (brown adipose tissue). As regards brown adipose tissue more particularly, the chronology of the cellular differentiation appears to be as follows: interstitial cells, brown adipocytes with a low level of differentiation, and mature brown adipocytes. Brown adipocytes are characterized by the presence of droplets of triglycerides and numerous mitochondria and by the presence of a particular protein, namely the above-mentioned uncoupling protein.
Stimulation of the proliferation and differentiation of brown adipose tissue depends especially on the .beta.-adrenergic receptors. The human .beta.3-adrenergic receptor has been characterized in the white adipose deposits of adults and in the brown adipose tissue of newborns and patients suffering from pheochromocytoma.
BAT is a tissue specializing in energy dissipation in the form of heat. It is found in most newborn mammals.
It is the major site of energy storage and mobilization; its role as an endocrine, autocrine and intracrine organ has also been established.
Cell lines produced in mice [murine line 3T3, line F44-2A (Green et al., Cell, 1975, 5, 19-27 and Cell, 1976, 7, 105-113)], as well as stromal vascular cells of adipose tissue, have also been the object of study insofar as preadipocytes are present in the vascular-stromal compartment (G. Ailhaud et al., Int. J. Obesity, 1992, 16, (suppl. 2), S17-S21).
However, these different lines or cells are not suitable for studying the physiopathology of the human metabolism. Consequently, there is a need to control metabolic diseases, especially obesity and diabetes, in man, both from the pharmacological point of view (model for the pharmacological study of lipolytic agents) and from the therapeutic point of view.
Now, it has hitherto been impossible to obtain lines of human preadipocytes which are capable of being maintained in culture for a sufficiently long time to be able to serve effectively as a model for studying lipolytic agents, on the one hand, and also to be suitable for use as therapeutic agents (in gene therapy, for example), on the other hand. In fact, the experiments performed on human adipocytes in primary culture are difficult to reproduce and difficult to carry out systematically.
The Applicant consequently set itself the task of providing cell lines, from brown or white adipose tissue, which are useful both as a model for studying lipolytic agents and as therapeutic agents (hyper-
REFERENCES:
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Stephane Krief et al., "Transcriptional Modulation by n-Butyric Acid of .beta.1, .beta.2- , and .beta.3-Adrenergic Receptor Balance in 3T3-F442A Adipocytes", The Journal of Biological Chemistry, vol. 269, No. 9, Mar. 4, 1994, pp. 6664-6670.
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Strosberg Arthur Donny
Zilberfarb Vladimir
Centre National de la Recherche Scientifique--CNRS
Yucel Remy
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