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Identification of a Cytochrome P4502E1/Bid/C1q-dependent Axis Mediating Inflammation in Adipose Tissue after Chronic Ethanol Feeding to Mice*
- Publication Year :
- 2011
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2011.
-
Abstract
- Chronic, heavy alcohol exposure results in inflammation in adipose tissue, insulin resistance, and liver injury. Here we have identified a CYP2E1/Bid/C1q-dependent pathway that is activated in response to chronic ethanol and is required for the development of inflammation in adipose tissue. Ethanol feeding for 25 days to wild-type (C57BL/6J) mice increased expression of multiple markers of adipose tissue inflammation relative to pair-fed controls independent of increased body weight or adipocyte size. Ethanol feeding increased the expression of CYP2E1 in adipocytes, but not stromal vascular cells, in adipose tissue and Cyp2e1(-/-) mice were protected from adipose tissue inflammation in response to ethanol. Ethanol feeding also increased the number of TUNEL-positive nuclei in adipose tissue of wild-type mice but not in Cyp2e1(-/-) or Bid (-/-) mice. Apoptosis contributed to adipose inflammation, as the expression of multiple inflammatory markers was decreased in mice lacking the Bid-dependent apoptotic pathway. The complement protein C1q binds to apoptotic cells, facilitating their clearance and activating complement. Making use of C1q-deficient mice, we found that activation of complement via C1q provided the critical link between CYP2E1/Bid-dependent apoptosis and onset of adipose tissue inflammation in response to chronic ethanol. In summary, chronic ethanol increases CYP2E1 activity in adipose, leading to Bid-mediated apoptosis and activation of complement via C1q, finally resulting in adipose tissue inflammation. Taken together, these data identify a novel mechanism for the development of adipose tissue inflammation that likely contributes to the pathophysiological effects of ethanol.
- Subjects :
- medicine.medical_specialty
Stromal cell
FGF21
Adipose tissue macrophages
Adipose tissue
Inflammation
Apoptosis
Biology
Biochemistry
chemistry.chemical_compound
Mice
Internal medicine
Adipocyte
medicine
Adipocytes
Animals
Molecular Biology
Mice, Knockout
Ethanol
Complement C1q
Central Nervous System Depressants
Molecular Bases of Disease
Cytochrome P-450 CYP2E1
Cell Biology
CYP2E1
Complement system
Endocrinology
chemistry
Adipose Tissue
Female
medicine.symptom
BH3 Interacting Domain Death Agonist Protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c11ca068cbd6f6a0ad913734c3a333db