Adipose Lipocalin 2 overexpression protects against age-related decline in thermogenic function of adipose tissue and metabolic deterioration
| Autor: | Yingjie Wu, David A. Bernlohr, Jessica A. Deis, Chengyu Liu, Xiaoli Chen, Hong Guo |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Lipocalin 2 0301 basic medicine Aging lcsh:Internal medicine medicine.medical_specialty Adipose Tissue White Adipose tissue 030209 endocrinology & metabolism White adipose tissue Adipose beiging Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance AMP-Activated Protein Kinase Kinases Lipocalin-2 Fibrosis Internal medicine Adipocyte medicine Animals lcsh:RC31-1245 Molecular Biology 2. Zero hunger business.industry Thermogenesis Cell Biology Adipose Tissue Beige Lipid Metabolism medicine.disease 3. Good health Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology Liver chemistry Adipogenesis Healthspan Original Article Steatosis business Protein Kinases Dyslipidemia |
| Zdroj: | Molecular Metabolism, Vol 24, Iss, Pp 18-29 (2019) Molecular Metabolism |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2019.03.007 |
| Popis: | Objectives Aging increases the risk for development of adipose tissue dysfunction, insulin resistance, dyslipidemia, and liver steatosis. Lipocalin 2 (Lcn2) deficient mice are more prone to diet-induced obesity and metabolic dysfunction, indicating a protective role for Lcn2 in younger mice. In this study, we determined whether overexpressing Lcn2 in adipose tissue can protect against age-related metabolic deterioration. Methods We developed ap2-promoter-driven Lcn2 transgenic (Tg) mice and aged Lcn2 Tg mice for the metabolic assessments. Results We found decreased adipocyte size in inguinal white adipose tissue (iWAT) from 10-month-old Lcn2 Tg mice relative to WT. This was accompanied by increased markers of adipogenesis in iWAT and attenuation of the age-related decline in AMP-activated protein kinase (AMPK) phosphorylation in adipose tissue depots. In addition to improvements in adipose tissue function, whole-body metabolic homeostasis was maintained in aged Lcn2 Tg mice. This included improved glucose tolerance and reduced serum triglycerides in older Lcn2 Tg mice relative to WT mice. Further, liver morphology and liver lipid levels were improved in older Lcn2 Tg mice, alongside a decrease in markers of liver inflammation and fibrosis. Conclusions We demonstrate that overexpression of Lcn2 in adipose tissue not only preserves adipose tissue function during aging but also promotes maintenance of glucose tolerance, decreases dyslipidemia, and prevents liver lipid accumulation and steatosis. Highlights • Lcn2 overexpression in adipose tissue promotes beiging of iWAT and BAT mitochondrial oxidation. • Lcn2 overexpression in adipose tissue improves thermogenic adaptation to cold in younger mice. • Adipose Lcn2 overexpression prevents age-related decline in thermogenic gene expression in brown and beige fat tissue. • Lcn2 overexpression in adipose tissue preserves adipose tissue function during aging. • Adipose Lcn2 overexpression promotes metabolic homeostasis and prevents age-related liver lipid accumulation. |
| Databáze: | OpenAIRE |
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