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Food reward depends on TLR4 activation in dopaminergic neurons
- Source :
- Pharmacological Research. 169:105659
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- The rising prevalence of obesity and being overweight is a worldwide health concern. Food reward dysregulation is the basic factor for the development of obesity. Dopamine (DA) neurons in the ventral tegmental area (VTA) play a vital role in food reward. Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor that can be activated by saturated fatty acids. Here, we show that the deletion of TLR4 specifically in DA neurons increases body weight, increases food intake, and decreases food reward. Conditional deletion of TLR4 also decreased the activity of DA neurons while suppressing the expression of tyrosine hydroxylase (TH) in the VTA, which regulates the concentration of DA in the nucleus accumbens (NAc) to affect food reward. Meanwhile, AAV-Cre-GFP mediated VTA-specific TLR4-deficient mice recapitulates food reward of DAT-TLR4-KO mice. Food reward could be rescued by re-expressing TLR4 in VTA DA neurons. Moreover, effects of intra-VTA infusion of lauric acid (a saturated fatty acid with 12 carbon) on food reward were abolished in mice lacking TLR4 in DA neurons. Our study demonstrates the critical role of TLR4 signaling in regulating the activity of VTA DA neurons and the normal function of the mesolimbic DA system that may contribute to food reward.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Blotting, Western
Fluorescent Antibody Technique
Biology
Nucleus accumbens
03 medical and health sciences
0302 clinical medicine
Reward
Dopamine
Internal medicine
medicine
Animals
Receptor
Mice, Knockout
Pharmacology
Tyrosine hydroxylase
Dopaminergic Neurons
Dopaminergic
Mice, Inbred C57BL
Toll-Like Receptor 4
Ventral tegmental area
030104 developmental biology
Endocrinology
medicine.anatomical_structure
nervous system
Food
030220 oncology & carcinogenesis
Saturated fatty acid
TLR4
Conditioning, Operant
psychological phenomena and processes
medicine.drug
Subjects
Details
- ISSN :
- 10436618
- Volume :
- 169
- Database :
- OpenAIRE
- Journal :
- Pharmacological Research
- Accession number :
- edsair.doi.dedup.....759c7ee5344c560fdff7c5870a4481bd