Steven R. Smith, M.D.
Molecular Endocrinology Lab
adipocytes in vitro
Director, Human Phenotyping Unpublished data to stimulate
Core, CNRU discussion
Baton Rouge, LA, USA
An in-vitro model for early
Shortfalls with current models:
– Most are murine
– Most examine ‘committed ’ cells;
– Intuitive to believe that the step from
mesenchymal stem cell to
preadipocyte is a regulated event.
Signaling in human adipocytes
in-vitro model systems Advantages:
(1) human mesenchymal – reagents cross-over to
stem cells (hMSC) & clinical studies
(2) SGBS cells – opportunities for
[Wabitsch, 2001] signaling systems that
(3) primary human are not present in rodent
adipocytes and S.V. cell lines; e.g. agouti
– hMSC more expensive
– reagents don’t cross over
into rodent models
Stem Cell Osteoblast, chondrocyte, tenocyte...
Other regulatory systems include:
Wnt 5a/10, IGF-1, TNF- α, MCRs, et cetera
Human mesenchymal stem cells
• Modified the methods of Pittenger, et al.
• hMSC isolated from bone marrow
• Purified by inverse selection
• Differentiate into:
– Neurons – Tenocytes
– Skeletal muscle – Chondrocytes
– Adipocytes – Osteoblasts
1. Pittenger MF, et al.: Multilineage potential of adult human mesenchymal stem cells. Science 284:143-147,
2. Human Mesenchymal Stem Cells as an in Vitro Model for Human Adipogenesis Lenka Janderová, Michele
McNeil, Angela N. Murrell, Randall L. Mynatt and Steven R. Smith Obesity Research 11:65-74 (2003)
We have identified two compounds
that work as well as the TZD’s to
promote fat cell differentiation in vitro.
Our model system is human
mesenchymal stem cells.
Our read-out is oil-red-O staining
which measures lipid storage.
• Oltipraz is also an anti-carcinogen.
Safety data from a large clinical trial:
’Protective alterations in phase 1 and 2 metabolism of aflatoxin B1 by
oltipraz in residents of Qidong, People's Republic of China’
J Natl Cancer Inst. 1999 Feb 17;91(4):347-54.
• potential drug for the treatment of
Alzheimer´s disease and other
• Dithiolthione compounds for the treatment
of neurological disorders and for memory
enhancement – WO109118A2 with a
patented synthesis of Oltipraz. (Edenland
Holdings, Baybush, Ireland now Hollis-Eden)
• The original US patent from Rhône-Poulenc
(Aventis): 1,2-Dithiole derivatives –
US4110450 which is based on a French
patent from 1963.
Differentiation promoters are sometimes
cell type specific
• Compound A = tBHQ
• Compound B = oltipraz
• Both are inducers of ‘endogenous
antioxidant enzymes’ such as NQO,
HO1, etc. via nrf2