Matrix Metalloproteinase 14 Plays a Key Role in Adipose Tissue Expansion in Obese Mice
Matrix metalloproteinase 14 (MMP14) is a pericellular collagenase expressed at high levels in adipose tissue. Li et al. (e00564-19) used an adipose tissue-specific and doxycycline-inducible MMP14 overexpression model to study the effects of this factor in obese mice. They found that overexpressing MMP14 in established obese fat leads to unhealthy metabolic effects via the production of endotrophin, a known fibrotic factor that triggers local inflammation. They further revealed that hypoxia-induced hypoxia-inducible factor 1α binds to the MMP14 promoter to upregulate MMP14 expression in obese fat. These findings suggest that MMP14 may be a key player in adipose tissue remodeling during the development of obesity.
Targeting IDOL Improves Cognitive Function and Aβ Pathology in a Mouse Model of Alzheimer’s Disease
The function of lipoprotein receptors in the brain has been linked to the development of Alzheimer’s disease-like pathology and cognitive impairment in mouse models. Low-density lipoprotein receptor (LDLR) is a major ApoE receptor in the brain that strongly regulates Aβ clearance and amyloid plaque deposition. Increasing glial LDLR levels has been suggested as a therapeutic strategy for Alzheimer’s disease. Gao et al. (e00518-19) show that therapeutically reducing the level of the E3 ubiquitin ligase IDOL, a negative regulator of LDLR, increases brain LDLR protein levels, ameliorates amyloidosis, and improves cognitive function in the APP/PS1 mouse model. Furthermore, IDOL reduction was found to enhance the lysosomal function of microglia and promote the phagocytic clearance of Aβ. These findings suggest that targeting the activity of the IDOL-LDLR pathway could have therapeutic utility in Alzheimer’s disease.
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