SignificanceThe liver secretes lipids in a controlled manner despite vast changes in its internal lipid content. This buffering function of the liver is essential for lipid/energy homeostasis, but its molecular and cellular mechanism is unknown. We show that motor protein kinesin transports lipid droplets (LDs) to the endoplasmic reticulum (ER) in liver cells, engineering ER−droplet contacts and supplying lipids to the ER for secretion as lipoprotein. However, when fasting induces massive lipid accumulation in liver, kinesin is removed from LDs, inhibiting lipid supply to the ER and homeostatically tempering lipid secretion from liver in a fasted state. Interestingly, reducing kinesin also blocks propagation of hepatitis-C virus inside liver cells, possibly because viral proteins cannot transfer from the ER to LDs.

Triglyceride-rich lipid droplets (LDs) are catabolized with high efficiency in hepatocytes to supply fatty acids for producing lipoprotein particles. Fasting causes a massive influx of adipose-derived fatty acids into the liver. The liver in the fasted state is therefore bloated with LDs but, remarkably, still continues to secrete triglycerides at a constant rate. Here we show that insulin signaling elevates phosphatidic acid (PA) dramatically on LDs in the fed state. PA then signals to recruit kinesin-1 motors, which transport LDs to the peripherally located smooth ER inside hepatocytes, where LDs are catabolized to produce lipoproteins. This pathway is down-regulated homeostatically when fasting causes insulin levels to drop, thus preventing dangerous elevation of triglycerides in the blood. Further, we show that a specific peptide against kinesin-1 blocks triglyceride secretion without any apparent deleterious effects on cells. Our work therefore reveals fundamental mechanisms that maintain lipid homeostasis across metabolic states and leverages this knowledge to propose a molecular target against hyperlipidemia.

All the four methods of dilation are equally safe and effective but both OSD and BD are advantageous in terms of lesser fluoroscopy time during dilation. OSD is much cheaper option when compared to BD, and therefore with more experience, it can become the preferable dilation method, especially in the developing countries.

We develop optical trapping methodology to precisely measure the force generated by motor-proteins on single organelles of unknown size in cell extract. Native motor-complexes can now be interrogated functionally, overcoming limitations of assays with purified motors coated on artificial beads. Forces, number and activity of kinesin-1 is measured on motile lipid droplets isolated from liver of normal and fasted rats to detect a correlation between metabolic state and kinesin-1 activity.

The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and for developing novel strategies for the treatment of associated infertility and pain. In this study, we investigated protein expression analysis of eutopic endometrium from women with and without endometriosis. The proteomic analysis revealed molecular dysregulation of more than 70 proteins in the proliferative phase of eutopic endometrium in stage IV and secretory phase of stage II, III and IV endometriosis. Using mass spectrometry, 48 proteins spots which were consistently differentially expressed from stage II to IV endometriosis were identified. The differentially expressed proteins include structural proteins, proteins involved in stress response, protein-folding and protein-turnover, immunity, energy production, signal transduction, RNA biogenesis, protein biosynthesis, and nuclear proteins. Immunoblot and immunohistochemical analyses confirmed the observed changes in eight representative proteins. The present study provides identification of new players that have a potential role in the initiation and progression of endometriosis and also sets a framework for further investigations on mechanisms underlying the pathogenesis of endometriosis.