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Saturated Fatty Acids Produce an Inflammatory Response Predominantly through the Activation of TLR4 Signaling in Hypothalamus: Implications for the Pathogenesis of Obesity
- Source :
- The Journal of Neuroscience. 29:359-370
- Publication Year :
- 2009
- Publisher :
- Society for Neuroscience, 2009.
-
Abstract
- In animal models of diet-induced obesity, the activation of an inflammatory response in the hypothalamus produces molecular and functional resistance to the anorexigenic hormones insulin and leptin. The primary events triggered by dietary fats that ultimately lead to hypothalamic cytokine expression and inflammatory signaling are unknown. Here, we test the hypothesis that dietary fats act through the activation of toll-like receptors 2/4 and endoplasmic reticulum stress to induce cytokine expression in the hypothalamus of rodents. According to our results, long-chain saturated fatty acids activate predominantly toll-like receptor 4 signaling, which determines not only the induction of local cytokine expression but also promotes endoplasmic reticulum stress. Rats fed on a monounsaturated fat-rich diet do not develop hypothalamic leptin resistance, whereas toll-like receptor 4 loss-of-function mutation and immunopharmacological inhibition of toll-like receptor 4 protects mice from diet-induced obesity. Thus, toll-like receptor 4 acts as a predominant molecular target for saturated fatty acids in the hypothalamus, triggering the intracellular signaling network that induces an inflammatory response, and determines the resistance to anorexigenic signals.
- Subjects :
- Male
medicine.medical_specialty
Indoles
medicine.medical_treatment
Hypothalamus
Biology
Antibodies
Mice
Internal medicine
medicine
Animals
Immunoprecipitation
Obesity
RNA, Messenger
Rats, Wistar
Receptor
Mice, Inbred C3H
Leptin receptor
General Neuroscience
Leptin
Insulin
Endoplasmic reticulum
Body Weight
Fatty Acids
Articles
Mice, Mutant Strains
Toll-Like Receptor 2
Rats
Toll-Like Receptor 4
Disease Models, Animal
Endocrinology
Gene Expression Regulation
Mutation
Cytokines
Microglia
Intracellular
Signal Transduction
Hormone
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....0e3e294a8ccfb208cc06d0031705397d