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Salsalate ameliorates metabolic disturbances by reducing inflammation in spontaneously hypertensive rats expressing human C-reactive protein and by activating brown adipose tissue in nontransgenic controls
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 6, p e0179063 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science, 2017.
-
Abstract
- Chronic low-grade inflammation plays an important role in the pathogenesis of insulin resistance. In the current study, we tested the effects of salsalate, a non-steroidal anti-inflammatory drug, in an animal model of inflammation and metabolic syndrome using spontaneously hypertensive rats (SHR) that transgenically express human C-reactive protein (SHR-CRP rats). We treated 15-month-old male transgenic SHR-CRP rats and nontransgenic SHR with salsalate (200 mg/kg/day) mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP and SHR rats were fed a standard diet without salsalate. In the SHR-CRP transgenic strain, salsalate treatment decreased circulating concentrations of the inflammatory markers TNF-α and MCP-1, reduced oxidative stress in the liver and kidney, increased sensitivity of skeletal muscles to insulin action and improved tolerance to glucose. In SHR controls with no CRP-induced inflammation, salsalate treatment reduced body weight, decreased concentrations of serum free fatty acids and total and HDL cholesterol and increased palmitate oxidation and incorporation in brown adipose tissue. Salsalate regulated inflammation by affecting the expression of genes from MAPK signalling and NOD-like receptor signalling pathways and lipid metabolism by affecting hepatic expression of genes that favour lipid oxidation from PPAR-α signalling pathways. These findings suggest that salsalate has metabolic effects beyond suppressing inflammation.
- Subjects :
- 0301 basic medicine
Physiology
medicine.medical_treatment
lcsh:Medicine
Gene Expression
Fatty Acids, Nonesterified
Pathology and Laboratory Medicine
Biochemistry
Animals, Genetically Modified
Endocrinology
Adipose Tissue, Brown
Brown adipose tissue
Salsalate
Medicine and Health Sciences
Insulin
lcsh:Science
Immune Response
Metabolic Syndrome
Multidisciplinary
Chemistry
Organic Compounds
Monosaccharides
Chemical Reactions
Salicylates
medicine.anatomical_structure
C-Reactive Protein
Adipose Tissue
Liver
Physical Sciences
Hypertension
Brown Adipose Tissue
medicine.symptom
Anatomy
medicine.drug
Research Article
medicine.medical_specialty
Immunology
Carbohydrates
Inflammation
NLR Proteins
03 medical and health sciences
Insulin resistance
Signs and Symptoms
Lipid oxidation
Diagnostic Medicine
Internal medicine
Oxidation
medicine
Genetics
Animals
Humans
PPAR alpha
Diabetic Endocrinology
Endocrine Physiology
Tumor Necrosis Factor-alpha
lcsh:R
Organic Chemistry
Chemical Compounds
Biology and Life Sciences
Lipid metabolism
Cell Biology
medicine.disease
Lipid Metabolism
Hormones
Rats
Oxidative Stress
030104 developmental biology
Biological Tissue
Glucose
lcsh:Q
Metabolic syndrome
Insulin Resistance
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....24173965fa12a8bad7197b5a9047dc1f