Sustained activation of autophagy suppresses adipocyte maturation via a lipolysis-dependent mechanism.

Dysregulation of macroautophagy/autophagy is implicated in obesity and insulin resistance. However, it remains poorly defined how autophagy regulates adipocyte development. Using adipose-specific rptor/raptor knockout (KO), atg7 KO and atg7 rptor double-KO mice, we show that inhibiting MTORC1 by RPTOR deficiency led to autophagic sequestration of lipid droplets, formation of LD-containing lysosomes, and elevation of basal and isoproterenol-induced lipolysis in vivo and in primary adipocytes. Despite normal differentiation at an early phase, progressive degradation and shrinkage of cellular LDs and downregulation of adipogenic markers PPARG and PLIN1 occurred in terminal differentiation of rptor KO adipocytes, which was rescued by inhibiting lipolysis or lysosome. In contrast, inactivating autophagy by depletion of ATG7 protected adipocytes against RPTOR deficiency-induced formation of LD-containing lysosomes, LD degradation, and downregulation of adipogenic markers in vitro. Ultimately, atg7 rptor double-KO mice displayed decreased lipolysis, restored adipose tissue development, and upregulated thermogenic gene expression in brown and inguinal adipose tissue compared to RPTOR-deficient mice in vivo. Collectively, our study demonstrates that autophagy plays an important role in regulating adipocyte maturation via a lipophagy and lipolysis-dependent mechanism. ABBREVIATIONS: ATG7: autophagy related 7; BAT: brown adipose tissue; CEBPB/C/EBPß: CCAAT enhancer binding protein beta; DGAT1: diacylglycerol O-acyltransferase 1; eWAT: epididymal white adipose tissue; iWAT: inguinal white adipose tissue; KO: knockout; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; PLIN1: perepilin 1; PNPLA2/ATGL: patatin-like phospholipase domain containing 2; PPARG/PPARγ: peroxisome proliferator activated receptor gamma; RPTOR: regulatory associated protein of MTOR complex1; TG: triglyceride; ULK1: unc-51 like kinase 1; UCP1: uncoupling protein 1; WAT: white adipose tissue.

Activation of matrix metalloproteinase in dorsal hippocampus drives improvement in spatial working memory after intra-VTA nicotine infusion in rats.

The hippocampus receives dopaminergic projections from the ventral tegmental area (VTA) and substantia nigra. These inputs appear to provide a modulatory signal that influences hippocampus-dependent behaviors. Enhancements in working memory performance have been previously reported following acute smoking/nicotine exposure. However, the underlying mechanism remains unclear. This study investigated the effects of nicotine on spatial working memory (SWM) and the mechanisms involved. Delayed alternation T-maze task was used to assess SWM. In situ and gel gelatin zymography were used to detect matrix metalloproteinase-9 (MMP-9) in SWM. Systemic or local (intra-VTA) administration of nicotine significantly improves SWM, which was accompanied by increased MMP-9 activity in dorsal hippocampus (dHPC). Intra-dHPC administration of MMP inhibitor FN-439 abolished the memory enhancement induced by intra-VTA nicotine infusion. FN-439 had no effect on locomotor behavior. Our data suggest that intra-VTA nicotine infusion activates MMP-9 in dHPC to improve SWM in rats.

The Department of Defense and Homeland Security relationship: Hurricane Katrina through Hurricane Irene.

This research explored federal intervention with the particular emphasis on examining how a collaborative relationship between Department of Defense (DOD) and Homeland Security (DHS) led to greater effectiveness between these two federal departments and their subordinates (United States Northern Command and Federal Emergency Management Agency, respectively) during the preparation and response phases of the disaster cycle regarding US continental-based hurricanes. Through the application of a two-phased, sequential mixed methods approach, this study determined how their relationship has led to longitudinal improvements in the years following Hurricane Katrina, focusing on hurricanes as the primary unit of analysis.

Quantifying effectiveness in emergency management.

This study looked at the relationship between the Departments of Defense (DOD) and Homeland Security (DHS). Moreover, it reviewed the interface between their two subordinate organizations (Northern Command under DOD and the Federal Emergency Management Agency under DHS) with primacy over domestic disasters. Understanding the importance of intergovernmental relations (IGRs), the article dissected the interrelatedness of these organizations regarding hurricanes and the subsequent involvement of federal preparation and response efforts. The informal networked relationships were evaluated using regression analysis focusing on secondary sources of data and several variables. The vitality of collaborative networks is grounded in literature and has been espoused by Waugh and Streib in the world of emergency management; this study expanded on their premise.