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ErbB4 deletion predisposes to development of metabolic syndrome in mice
- Source :
- American Journal of Physiology-Endocrinology and Metabolism. 315:E583-E593
- Publication Year :
- 2018
- Publisher :
- American Physiological Society, 2018.
-
Abstract
- ErbB4, a member of the EGF receptor family, plays a variety of roles in physiological and pathological states. Genetic studies have indicated a link between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study we found that mice with ErbB4 deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4 deletion mice also exhibited increased amounts of subcutaneous and visceral fat, with increased serum leptin levels, compared with wild-type mice, whereas levels of adiponectin were not significantly different. Histologically, severe inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization, was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation. Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1 adipocytes had no effect on adipogenesis and lipolysis but significantly inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly increased glucose uptake in adipocytes isolated from wild-type mice, while these effects were significantly decreased in adipocytes isolated from ErbB4 deletion mice. In conclusion, our results indicate that ErbB4 may play an important role in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and adipose tissue inflammation may contribute to the development of MetS.
- Subjects :
- Leptin
Male
0301 basic medicine
Receptor, ErbB-4
Physiology
Endocrinology, Diabetes and Metabolism
Type 2 diabetes
Mice
ERBB4
Neuregulins
Metabolic Syndrome
education.field_of_study
Adipogenesis
Glucose Transporter Type 4
Adiponectin
medicine.symptom
Research Article
medicine.medical_specialty
Adipose Tissue, White
Subcutaneous Fat
Inflammation
Intra-Abdominal Fat
Biology
03 medical and health sciences
Insulin resistance
3T3-L1 Cells
Hyperinsulinism
Physiology (medical)
Internal medicine
medicine
Animals
Genetic Predisposition to Disease
Obesity
education
Pathological
Dyslipidemias
Neuregulin-4
Lipogenesis
Macrophages
medicine.disease
Dietary Fats
Fatty Liver
030104 developmental biology
Endocrinology
Hyperglycemia
Insulin Resistance
Metabolic syndrome
Gene Deletion
Subjects
Details
- ISSN :
- 15221555 and 01931849
- Volume :
- 315
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Endocrinology and Metabolism
- Accession number :
- edsair.doi.dedup.....7789169090e3f4ca0fec4e527aa4b10f