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 |
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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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