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Fibroblast growth factor 21 deficiency aggravates obesity-induced hypothalamic inflammation and impairs thermogenic response
- Source :
- Inflammation Research. 68:351-358
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Hypothalamic inflammation is closely associated with metabolic dysregulation. Fibroblast growth factor 21 (FGF21) is known to be an important metabolic regulator with anti-inflammatory properties. In this study, we investigated the effects of FGF21 deficiency on obesity-induced hypothalamic inflammation and thermogenic responses. FGF21-deficient mice and/or wild-type (WT) mice were fed a high-fat diet (HFD) for 12 weeks. FGF21-deficient mice fed an HFD showed increased levels of inflammatory cytokines compared with WT obese control, and this was accompanied by upregulation of gliosis markers in the hypothalamus. Expression of heat-shock protein 72, a marker of neuronal damage, was increased in the FGF21-deficient obese mice, and the expression of hypothalamic neuronal markers involved in anti-thermogenic or thermogenic responses was altered. Moreover, the protein level of uncoupling protein 1 and other thermogenic genes were markedly reduced in the brown adipose tissue of the FGF21-deficient obese mice. These findings suggest that FGF21 deficiency aggravates obesity-induced hypothalamic inflammation and neuronal injury, leading to alterations in hypothalamic neural circuits accompanied by a reduction of the thermogenic response.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
FGF21
Immunology
HSP72 Heat-Shock Proteins
Biology
Diet, High-Fat
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Adipose Tissue, Brown
Downregulation and upregulation
Internal medicine
Brown adipose tissue
medicine
Animals
Obesity
Receptor, Fibroblast Growth Factor, Type 1
Klotho Proteins
Inflammation
Mice, Knockout
Neurons
Pharmacology
Brain
Membrane Proteins
Thermogenesis
Metabolism
Thermogenin
Fibroblast Growth Factors
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Gliosis
Hypothalamus
030220 oncology & carcinogenesis
Cytokines
Atrophy
medicine.symptom
Subjects
Details
- ISSN :
- 1420908X and 10233830
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Inflammation Research
- Accession number :
- edsair.doi.dedup.....3afd0ec7faf7632525300e2177aa7800