CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance

Autor: Dan Liu, Meili Liu, Shaohua Li, Yan-xia Liu, Chenghui Yan, Xiaoxiang Tian, Yaling Han, Quanyu Zhang
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Physiology
medicine.medical_treatment
Adipose tissue
lcsh:Medicine
Haploinsufficiency
Pathology and Laboratory Medicine
Biochemistry
Fats
Mice
Endocrinology
Animal Cells
Medicine and Health Sciences
Adipocytes
Insulin
RNA
Small Interfering
lcsh:Science
Immune Response
Connective Tissue Cells
Multidisciplinary
Hydrolysis
Chemical Reactions
NF-kappa B
Lipids
Chemistry
Phenotype
Physiological Parameters
Adipose Tissue
Liver
Connective Tissue
Physical Sciences
Cytokines
medicine.symptom
Anatomy
Cellular Types
Research Article
medicine.medical_specialty
Heterozygote
Transgene
Lipolysis
Immunology
Inflammation
Mice
Transgenic
Biology
Diet
High-Fat
Transfection
03 medical and health sciences
Insulin resistance
Signs and Symptoms
Diagnostic Medicine
Internal medicine
3T3-L1 Cells
medicine
Animals
Obesity
Diabetic Endocrinology
Endocrine Physiology
lcsh:R
Body Weight
Biology and Life Sciences
Cell Biology
medicine.disease
Hormones
Mice
Inbred C57BL
Repressor Proteins
Disease Models
Animal
030104 developmental biology
Biological Tissue
lcsh:Q
Metabolic syndrome
Insulin Resistance
Zdroj: PLoS ONE
PLoS ONE, Vol 12, Iss 5, p e0176873 (2017)
ISSN: 1932-6203
Popis: Cellular repressor of E1A-stimulated genes 1 (CREG1) is a small glycoprotein whose physiological function is unknown. In cell culture studies, CREG1 promotes cellular differentiation and maturation. To elucidate its physiological functions, we deleted the Creg1 gene in mice and found that loss of CREG1 leads to early embryonic death, suggesting that it is essential for early development. In the analysis of Creg1 heterozygous mice, we unexpectedly observed that they developed obesity as they get older. In this study, we further studied this phenotype by feeding wild type (WT) and Creg1 heterozygote (Creg1+/-) mice a high fat diet (HFD) for 16 weeks. Our data showed that Creg1+/- mice exhibited a more prominent obesity phenotype with no change in food intake compared with WT controls when challenged with HFD. Creg1 haploinsufficiency also exacerbated HFD-induced liver steatosis, dyslipidemia and insulin resistance. In addition, HFD markedly increased pro-inflammatory cytokines in plasma and epididymal adipose tissue in Creg1+/- mice as compared with WT controls. The activation level of NF-κB, a major regulator of inflammatory response, in epididymal adipose tissue was also elevated in parallel with the cytokines in Creg1+/- mice. These pro-inflammatory responses elicited by CREG1 reduction were confirmed in 3T3-L1-derived adipocytes with CREG1 depletion by siRNA transfection. Given that adipose tissue inflammation has been shown to play a key role in obesity-induced insulin resistance and metabolic syndrome, our results suggest that Creg1 haploinsufficiency confers increased susceptibility of adipose tissue to inflammation, leading to aggravated obesity and insulin resistance when challenged with HFD. This study uncovered a novel function of CREG1 in metabolic disorders.
Databáze: OpenAIRE
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