Autophagy can remove excess or dysfunctional proteins and organelles to maintain cellular homeostasis. Browning of white adipose tissue increases the energy expenditure. Microtubules affinity regulated kinase 4 (Mark4) can regulate a variety of physiological processes. According to previous studies, we speculated that Mark4-autophagy-browning of white adipose tissue had certain linkages. Here, we established two autophagy models through serum starvation and rapamycin treatment and detected that the overexpression of Mark4 increased the expression of autophagy-related factors Beclin1, ATG7, and significantly decreased the autophagy substrate P62. Further tests showed that the overexpression of Mark4 promoted the conversion of autophagy marker protein LC3A to LC3B-II by activating the AMP-activated protein kinase (AMPK) pathway and inhibition of the AKT/mTOR signaling. Moreover, Mark4 decreased the expression of thermogenesis genes via promoting autophagy. These results indicated that Mark4 inhibited the browning of white adipose tissue via promoting autophagy. AMPK signaling pathway. By adding compound C, the phosphorylation of AMPK and the formation of LC3B-II were reduced while the level of autophagy substrate p62 was increased ( Figure 4A,B). The results of AKT pathway examination was opposite. The overexpression of Mark4 significantly inhibited the phosphorylation of AKT and mTOR, accompanied by an increase in LC3B-II and a decrease in P62. After treating with the AKT inhibitor MK2206, the phosphorylation levels of AKT, mTOR, and the protein level of P62 were significantly reduced. The LC3B-II expression was increased ( Figure 4C,D). These results indicated that Mark4 could regulate serum starvation-induced autophagy via the AMPK/AKT signal pathway.

Suppressor of cytokine signaling 2 (SOCS2) plays an important role in fat deposition, skeletal muscle, central nervous system development, and mitochondria biogenesis. Nevertheless, the regulatory mechanisms of SOCS2 on mitochondrial fatty acid oxidation (FAO) remain unclear. Leptin could inhibit food intake and increase thermogenesis through leptin receptor (LepR), which was present in the hypothalamus and certain peripheral organs, including adipose tissue. With strong interest, we focused on the connection between leptin and SOCS2 and their effect on FAO in adipocytes. In our study, we found that the mRNA level of SOCS2 and the protein levels of PGC-1α, CPT-1b, FAT, and p-ACC were elevated by leptin in the inguinal adipose tissue of mice. On the contrary, the protein levels of FABP4, FATP1, and FAS were declined. The genes related to fatty acid oxidation such as PGC-1α, NRF-1, TFAM, CPT-1b, AOX1, COX2, and UCP2 were attenuated by SOCS2, but elevated by leptin. Moreover, fatty acid oxidation enzyme MCAD, LCAD, and Cyt C levels were reduced in response to SOCS2. These reductions correspond well with the reduced release of free fatty acid and the reduction of mitochondrial complexes I and III by SOCS2. Furthermore, JAK2/AMPK pathway-specific inhibitors could block the mitochondrial FAO; hence, this pathway was implied to have a potential impact on FAO. Together, these studies suggested that SOCS2 had a negative effect on mitochondrial fatty acid oxidation, and the LepR/JAK2/AMPK pathway played a crucial role in this process.

The extracellular matrix (ECM) is a highly dynamic structural network and plays an essential role in cell behavior and regulation during metabolic homeostasis and obesity progression. Abnormal ECM remodeling impairs adipocyte plasticity required for diverse cellular functions. Collagen XV (ColXV) is a proteoglycan localized to the outermost layer of basement membranes (BMs) and forms a bridge between the BMs and the fibrillar collagen matrix. Nevertheless, how ColXV affects ECM composition and the reason for subsequent adipocyte apoptosis is still unclear. This report found, through RNA-seq data, that ColXV is linked to cell growth and ECM remodeling. Findings show that, in response to excessive expression of extracellular ColXV, the AMPK/mTORC1 pathway is strongly activated and triggers a cascade of mitochondrial apoptosis. This is the first study to make use of ECM three-dimensional reconstruction, based on decellularization in the adipose tissues and the study reveals that ColXV is an activation factor that alters ECM remodeling in adipose tissues. It was also demonstrated that the fibroblast growth factor 2 (FGF2)/fibroblast growth factor receptor 1 (FGFR1) axis involved in ECM remodeling is suppressed by ColXV due to reduction of FGF2 translocation to FGFR1. Furthermore, ColXV induced remodeling of ECM preceding apoptosis and continued to induce apoptosis in adipocytes. Collectively, our findings establish ColXV as a basement membrane collagen with homology to ColXVIII, indicating that it is one of the positive regulators for inducing ECM remodeling and further promoting adipocyte apoptosis.

Objective Timely availability of intravenous infusion pumps is critical for high-quality care delivery. Pumps are shared among hospital units, often without central management of their distribution. This study seeks to characterize unit-to-unit pump sharing and its impact on shortages, and to evaluate a system-control tool that balances inventory across all care areas, enabling increased availability of pumps. Materials and Methods A retrospective study of 3832 pumps moving in a network of 5292 radiofrequency and infrared sensors from January to November 2017 at The Johns Hopkins Hospital in Baltimore, Maryland. We used network analysis to determine whether pump inventory in one unit was associated with inventory fluctuations in others. We used a quasi-experimental design and segmented regressions to evaluate the effect of the system-control tool on enabling safe inventory levels in all care areas. Results We found 93 care areas connected through 67,111 pump transactions and 4 discernible clusters of pump sharing. Up to 17% (95% confidence interval, 7%-27%) of a unit’s pump inventory was explained by the inventory of other units within its cluster. The network analysis supported design and deployment of a hospital-wide inventory balancing system, which resulted in a 44% (95% confidence interval, 36%-53%) increase in the number of care areas above safe inventory levels. Conclusions Network phenomena are essential inputs to hospital equipment fleet management. Consequently, benefits of improved inventory management in strategic unit(s) are capable of spreading safer inventory levels throughout the hospital.