Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis.
Metabolic and inflammatory pathways crosstalk at many levels, and, while required for homeostasis, interaction between these pathways can also lead to metabolic dysregulation under conditions of chronic stress. Thus, we hypothesized that mechanisms might exist to prevent overt inflammatory responses during physiological fluctuations in nutrients or under nutrient-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 aberrant 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 resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty liver disease. We conclude that STAMP2 participates in integrating inflammatory and metabolic responses and thus plays a key role in systemic metabolic homeostasis.
Wellen
Kathryn E
KE
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Fucho
Raquel
R
Gregor
Margaret F
MF
Furuhashi
Masato
M
Morgan
Carlos
C
Lindstad
Torstein
T
Vaillancourt
Eric
E
Gorgun
Cem Z
CZ
Saatcioglu
Fahri
F
Hotamisligil
Gökhan S
GS
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005502:Food; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007249:Inflammation / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D024821:Metabolic Syndrome / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation
D007328:Insulin; D008565:Membrane Proteins; C436323:Tiarp protein, mouse; D005947:Glucose