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Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue
- Source :
- Cell reports 18(1), 225-236 (2017). doi:10.1016/j.celrep.2016.12.028
- Publication Year :
- 2016
-
Abstract
- Current worldwide figures suggest that obesity is pandemic. Understanding the underlying molecular mechanisms would help develop viable anti-obesity therapies. Here, we assess the influence of obesity-induced inflammation on white adipocyte cyclic guanosine monophosphate (cGMP) signaling, which is beneficial for adipocyte differentiation and thermogenesis. We find that murine gonadal and not inguinal fat is prone to obesity-induced inflammation. Correspondingly, the cGMP cascade is dysregulated in gonadal but not in inguinal fat of obese mice. Analysis of two independent human cohorts reveals a defective cGMP pathway only in visceral fat of obese subjects. Congruently, cGMP signaling is dysregulated in tumor necrosis factor α (TNF-α)-treated primary white adipocytes. TNF-α-mediated suppression of sGCβ1 is mediated via NF-κB, whereas PKG is repressed by JNK signaling. Additionally, TNF-α-activated JNK signaling suppresses PPARγ and aP2. Taken together, the intensity of obesity-induced inflammation dictates the amplitude of cGMP signaling dysregulation in white adipocytes through distinct pathways.
- Subjects :
- 0301 basic medicine
Male
metabolism [Cyclic GMP-Dependent Protein Kinases]
Mice, Obese
White adipose tissue
drug effects [Adipogenesis]
chemistry.chemical_compound
0302 clinical medicine
metabolism [Guanylate Cyclase]
Adipocyte
White Adipocytes
Cyclic GMP
Cells, Cultured
metabolism [Inflammation]
Adipogenesis
drug effects [Cell Differentiation]
complications [Obesity]
NF-kappa B
pharmacology [Tumor Necrosis Factor-alpha]
Cell Differentiation
physiology [Inguinal Canal]
Phenotype
metabolism [NF-kappa B]
Female
medicine.symptom
Signal Transduction
medicine.medical_specialty
drug effects [Signal Transduction]
pathology [Obesity]
MAP Kinase Signaling System
Adipose Tissue, White
Down-Regulation
Inguinal Canal
030209 endocrinology & metabolism
Inflammation
complications [Inflammation]
Biology
Models, Biological
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
drug effects [MAP Kinase Signaling System]
Internal medicine
metabolism [Obesity]
medicine
Cyclic GMP-Dependent Protein Kinases
metabolism [Gonads]
Animals
Humans
ddc:610
Obesity
Gonads
Cyclic guanosine monophosphate
metabolism [Adipose Tissue, White]
pathology [Inflammation]
metabolism [Cyclic GMP]
Tumor Necrosis Factor-alpha
Cgmp signaling
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
Solubility
drug effects [Down-Regulation]
Guanylate Cyclase
Thermogenesis
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 18
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Cell reports
- Accession number :
- edsair.doi.dedup.....6b9d6ddbc713dd79849d04a951af1a1f