Coordinated Regulation of Nutrient and
Inflammatory Responses by STAMP2
Is Essential for Metabolic Homeostasis
Kathryn E. Wellen,1 Raquel Fucho,1 Margaret F. Gregor,1 Masato Furuhashi,1 Carlos Morgan,1
Torstein Lindstad,2 Eric Vaillancourt,1 Cem Z. Gorgun,1 Fahri Saatcioglu,2 and Gòˆkhan S. Hotamisligil1,*
1Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, 02115, USA
2Department of Molecular Biosciences, University of Oslo, Postboks 1041, Blindern, 0316 Oslo, Norway
*Correspondence: ghotamis@hsph.harvard.edu
DOI 10.1016/j.cell.2007.02.049
SUMMARY
Metabolic and inflammatory pathways cross-
talk at many levels, and, while required for ho-
meostasis, interaction between these pathways
can also lead to metabolic dysregulation under
conditions of chronic stress. Thus, we hypothe-
sized that mechanisms might exist to prevent
overt inflammatory responses during physio-
logical fluctuations in nutrients or under nutri-
ent-rich conditions, and we identified the six-
transmembrane protein STAMP2 as a critical
modulator of this integrated response system
of inflammation and metabolism in adipocytes.
Lack of STAMP2 in adipocytes results in aber-
rant inflammatory responses to both nutrients
and acute inflammatory stimuli. Similarly, in
whole animals, visceral adipose tissue of
STAMP2/ mice exhibits overt inflammation,
and these mice develop spontaneous metabolic
disease on a regular diet, manifesting insulin re-
sistance, glucose intolerance, mild hyperglyce-
mia, dyslipidemia, and fatty liver disease. We
conclude that STAMP2 participates in integrat-
ing inflammatory and metabolic responses and
thus plays a key role in systemic metabolic
homeostasis.
INTRODUCTION
Cells and organisms must strike an appropriate balance
between nutrient sufficiency and surplus. Adequate
amounts of nutrients must be obtained in order for them
to survive and function normally. On the other hand,
chronic nutrient overload can lead to obesity as well as
to an array of associated metabolic disorders, incl