Epididymis cholesterol homeostasis and sperm fertilizing ability

Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

Black TiO_(2) nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild pho-totherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photo-thermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO_(2) nanoparticles. The results showed that when temperatures below 45 ◦C, PTT alone and PTT +PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO_(2) nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

Fluorescent visualization and evaluation of NPC1L1- mediated vesicular endocytosis during intestinal cholesterol absorption in mice

Excessive cholesterol absorption from intestinal lumen contributes to the pathogenesis of hypercholesterolemia,which is an independent risk factor for atherosclerotic cardiovascular disease.Niemann-Pick C1-like 1(NPC1L1)is a major membrane protein responsible for cholesterol absorption,in which the physiological role of vesicular endocytosis is still controversial,and it lacks a feasible tool to visualize and evaluate the endocytosis of NPC1L1 vesicles in vivo.Here,we genetically labeled endogenous NPC1L1 protein with EGFP in a knock-in mouse model,and demonstrated fluorescent visualization and evaluation of the endocytic vesicles of NPC1L1-cago during intestinal cholesterol absorption.The homozygous NPC1L1-EGFP mice have normal NPC1L1 expression pattern as well as cholesterol homeostasis on chow or high-cholesterol diets.The fluorescence of NPC1L1-EGFP fusion protein localizes at the brush border membrane of small intestine,and EGFP-positive vesicles is visualized beneath the membrane as early as 5 min post oral gavage of cholesterol.Of note,the vesicles colocalize with the early endosomal marker early endosome antigen 1(EEA1)and the filipin-stained free cholesterol.Pretreatment with NPC1L1 inhibitor ezetimibe inhibits the formation of these cholesterol-induced endocytic vesicles.Our data support the notion that NPC1L1-mediated cholesterol absorption is a vesicular endocytic process.NPC1L1-EGFP mice are a useful model for visualizing cellular NPC1L1-cargo vesicle itineraries and for evaluating NPC1L1 activity in vivo in response to diverse pharmacological agents and nutrients.

New insights into effects of Kaixin Powder on depression via lipid metabolism related adiponectin signaling pathway

Objective:To clarify the anti-depressive potential mechanisms of Kaixin Powder(KP),a drug that helps to prevent and treat depression and other mentaldiseases,from genome-wide transcriptome profiling.Methods:Transcriptome and KEGG pathway analysis were conducted on the hippocampus of depressed rats,then the differentially expressed genes were validated and serum concentration of lipid parameters were identified by enzymatic assays.Furthermore,high-fat diets induced depression-like behaviors in Syrian golden hamsters were conducted to verify the predicted molecular mechanisms acquired from the transcriptome analysis.Results:Transcriptome results revealed that the 24 differentially expressed genes(DEGs)in chronic mild stress(CMS)rats could be reversed after two weeks of KP treatment.The mechanisms of KP in treating depression firstly involved the regulation of several pathology modules,including lipid metabolism,synapse function and inflammation.KP could regulate imbalances of lipid homeostasis in high-fat diet induced depressive symptoms.Furthermore,it was validated that cholesterol metabolism dysfunction can be ameliorated by KP,which was correlated with upregulation of the AdipoR1-BDNF(brainderived neurotrophic factor)co-regulatory pathway.Conclusion:Taken together,our results demonstrated that KP not only alleviates depression via traditional mental illness targets,but it may also simulates the cholesterol metabolism and adiponectin signaling with multi-target characteristics.