The cryo-EM resolution revolution has heralded a new era in our understanding of eukaryotic lipid flippases with a rapidly growing number of high-resolution structures. Flippases belong to the P4 family of ATPases (type IV P-type ATPases) that largely follow the reaction cycle proposed for the more extensively studied cation-transporting P-type ATPases. However, unlike the canonical P-type ATPases, no flippase cargos are transported in the phosphorylation half-reaction. Instead of being released into the intracellular or extracellular milieu, lipid cargos are transported to their destination at the inner leaflet of the membrane. Recent flippase structures have revealed multiple conformational states during the lipid transport cycle. Nonetheless, critical conformational states capturing the lipid cargo \"in transit\" are still missing. In this review, we highlight the amazing structural advances of these lipid transporters, discuss various perspectives on catalytic and regulatory mechanisms in the literature, and shed light on future directions in further deciphering the detailed molecular mechanisms of lipid flipping.

According to current guidelines, the selection and intensity of lipid-effective therapies are based on the risk to be treated. The sole clinical categories of primary and secondary prevention of cardiovascular diseases result in over- and under-treatment, which may be a contributory cause of incomplete implementation of current guidelines in everyday practice. For the extent of benefit in cardiovascular outcome studies with lipid-lowering drugs, the importance of dyslipdemia for the pathogenesis of atherosclerosis-related diseases is crucial. Primary lipid metabolism disorders are characterized by life-long increased exposure to atherogenic lipoproteins. This article describes the relevance of new data for low density lipoprotein-effective therapy: inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), adenosine triphosphate (ATP) citrate lyase with bempedoic acid, and ANGPTL3 with special consideration of primary lipid metabolism disorders, which are insufficiently taken into account, or not taken into account at all, in current guidelines. This is due to their apparently low prevalence rate and thus the lack of large outcome studies. The authors also discuss the consequences of increased lipoprotein (a), which cannot be sufficiently reduced until the ongoing intervention studies examining antisense oligonucleotides and small interfering RNA (siRNA) against apolipoprotein (a) are completed. Another challenge in practice is the treatment of rare, massive hypertriglyceridemia, especially with the aim of preventing pancreatitis. For this purpose, the apolipoprotein C3 (ApoC3) antisense oligonucleotide volenasorsen is available, which binds to the mRNA for ApoC3 and lowers triglycerides by around three quarters.
UNASSIGNED: Nach aktuellen Leitlinien ergeben sich Auswahl und Intensität lipidwirksamer Therapien aus dem zu behandelnden Risiko. Die alleinigen klinischen Kategorien von Primär- und Sekundärprävention kardiovaskulärer Erkrankungen führen im Ergebnis zu Über- und Unterbehandlungen, was eine Mitursache für die geringe Umsetzung aktueller Leitlinien im praktischen Alltag sein könnte. Für das Ausmaß der Wirksamkeit von Lipidsenkern in kardiovaskulären Outcome-Studien ist entscheidend, welchen Stellenwert Lipidstoffwechselstörungen in der Pathogenese atherosklerosebedingter Erkrankungen haben. Primäre Fettstoffwechselstörungen zeichnen sich durch die lebenslang erhöhte Exposition gegenüber atherogenen Lipoproteinen aus. Die vorliegende Arbeit beschreibt den Stellenwert neuer Daten zur Low-density-Lipoprotein-wirksamen Therapie durch Hemmung von „proprotein convertase subtilisin/kexin type 9“ (PCSK9), der Adenosintriphosphat(ATP)-Citrat-Lyase mit Bempedoinsäure und von ANGPTL3 – unter besonderer Berücksichtigung der primären Fettstoffwechselstörungen. Denn diese sind in den Leitlinien unzureichend oder überhaupt nicht berücksichtigt, was zum Teil ihrer scheinbaren Seltenheit und damit dem Fehlen großer Outcome-Studien geschuldet ist. Wir gehen auch auf die Konsequenzen eines erhöhten Lipoprotein(a)-Spiegels ein, der bis zum Abschluss laufender Interventionsstudien, in denen Antisense-Oligonukleotide und „small interfering RNA“ (siRNA) gegen Apolipoprotein(a) erprobt werden, bislang nicht ausreichend abgesenkt werden kann. Eine Herausforderung in der Praxis ist auch die Behandlung seltener massiver Hypertriglyzeridämien, insbesondere mit dem Ziel, Pankreatitiden vorzubeugen. Zu diesem Zweck wird das Apolipoprotein-C3(ApoC3)-Antisense-Oligonukleotid Volanesorsen eingesetzt, das an die „messenger RNA“ (mRNA) für ApoC3 bindet und Triglyzeride um rund drei Viertel absenkt.

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Familial hypercholesterolemia (FH) is the most common monogenic disorder. Due to the marked elevation of cardiovascular risk, the early detection, diagnosis, and proper management of this disorder are critical. Herein, the 2022 Korean guidance on this disease is presented. Clinical features include severely elevated low-density lipoprotein-cholesterol (LDL-C) levels, tendon xanthomas, and premature coronary artery disease. Clinical diagnostic criteria include clinical findings, family history, or pathogenic mutations in the LDLR, APOB, or PCSK9. Proper suspicion of individuals with typical characteristics is essential for screening. Cascade screening is known to be the most efficient diagnostic approach. Early initiation of lipid-lowering therapy and the control of other risk factors are important. The first-line pharmacological treatment is statins, followed by ezetimibe, and PCSK9 inhibitors as required. The ideal treatment targets are 50% reduction and <70 mg/dL or <55 mg/dL (in the presence of vascular disease) of LDL-C, although less strict targets are frequently used. Homozygous FH is characterized by untreated LDL-C >500 mg/dL, xanthoma since childhood, and family history. In children, the diagnosis is made with criteria, including items largely similar to those of adults. In women, lipid-lowering agents need to be discontinued before conception.

Familial hypercholesterolemia (FH) is the most common monogenic disorder. Due to the marked elevation of cardiovascular risk, the early detection, diagnosis, and proper management of this disorder are critical. Herein, the 2022 Korean guidance on this disease is presented. Clinical features include severely elevated low-density lipoprotein cholesterol (LDL-C) levels, tendon xanthomas, and premature coronary artery disease. Clinical diagnostic criteria include clinical findings, family history, or pathogenic mutations in the LDLR, APOB, or PCSK9. Proper suspicion of individuals with typical characteristics is essential for screening. Cascade screening is known to be the most efficient diagnostic approach. Early initiation of lipid-lowering therapy and the control of other risk factors are important. The first-line pharmacological treatment is statins, followed by ezetimibe, and PCSK9 inhibitors as required. The ideal treatment targets are 50% reduction and < 70 or < 55 mg/dL (in the presence of vascular disease) of LDL-C, although less strict targets are frequently used. Homozygous FH is characterized by untreated LDL-C > 500 mg/dL, xanthoma since childhood, and family history. In children, the diagnosis is made with criteria, including items largely similar to those of adults. In women, lipid-lowering agents need to be discontinued before conception.

BACKGROUND: Despite several RNA-Seq and microarray studies on differentially expressed genes (DEGs) between high- and low-abdominal fat deposition in different broiler lines, to our knowledge, gene coexpression analysis across multiple broiler lines has rarely been reported. Here, we constructed a consensus gene coexpression network focused on identifying consensus gene coexpression modules associated with abdominal fat deposition across multiple broiler lines using two public RNA-Seq datasets (GSE42980 and GSE49121).
RESULTS: In the consensus gene coexpression network, we identified eight consensus modules significantly correlated with abdominal fat deposition across four broiler lines using the consensus module analysis function in the weighted gene coexpression network analysis (WGCNA) package. The eight consensus modules were moderately to strongly preserved in the abdominal fat RNA-Seq dataset of another broiler line (SRP058295). Furthermore, we identified 5462 DEGs between high- and low-abdominal fat lines (FL and LL) (GSE42980) and 6904 DEGs between high- and low-growth (HG and LG) (GSE49121), including 1828 overlapping DEGs with similar expression profiles in both datasets, which were clustered into eight consensus modules. Pyruvate metabolism, fatty acid metabolism, and steroid biosynthesis were significantly enriched in the green, yellow, and medium purple 3 consensus modules. The PPAR signaling pathway and adipocytokine signaling pathway were significantly enriched in the green and purple consensus modules. Autophagy, mitophagy, and lysosome were significantly enriched in the medium purple 3 and yellow consensus modules.
CONCLUSIONS: Based on lipid metabolism pathways enriched in eight consensus modules and the overexpression of numerous lipogenic genes in both FL vs. LL and HG vs. LG, we hypothesize that more fatty acids, triacylglycerols (TAGs), and cholesterol might be synthesized in broilers with high abdominal fat than in broilers with low abdominal fat. According to autophagy, mitophagy, and lysosome enrichment in eight consensus modules, we inferred that autophagy might participate in broiler abdominal fat deposition. Altogether, these studies suggest eight consensus modules associated with abdominal fat deposition in broilers. Our study also provides an idea for investigating the molecular mechanism of abdominal fat deposition across multiple broiler lines.

Background: Neonates and infants are susceptible to skin barrier disruption as their skin anatomically and functionally is still developing. The process of skin acidification plays a vital role in barrier maturation and the activation of enzymes involved in the extracellular processing of stratum corneum lipids. The current consensus paper explores challenges, and current treatment approaches in neonatal and infant normal and sensitive skin and the role of ceramides containing moisturizers. Methods: For this purpose, an expert panel of pediatric dermatologists and dermatologists discussed information from systematic literature searches, coupled with expert opinion and experience of the panel, to adopt eight statements. The consensus process consisted of a modified Delphi technique. Results: During the first years after birth, the neonatal and infant skin is more permeable to topical agents and, therefore, requires particular caution with topical skincare regimens. Mildly acidic or pH-neutral cleansers have benefits for neonates and infants. Skincare for neonates and infants should be safe, effective, and fragrance free as well as sensitizing agent-free. Additionally, the skincare should be pleasant to use, containing ingredients that benefit the lipid and water content of the SC, such as those products containing ceramides. Conclusion: Taking into consideration the maturation process of neonatal and infant skin, the application of moisturizers and cleansers containing barrier lipids may help maintain the protective skin barrier and soothe with long-term moisturizing benefits. J Drugs Dermatol. 2020;19(8) 769-776: doi:10.36849/JDD.2020.5252 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

T***he current control of low-density lipoprotein cholesterol among patients with atherosclerotic cardiovascular disease is very low and this is associated with an increase of cardiovascular outcomes. In addition, the latter this happens, the risk will be greater. This is mainly due to an insufficient use of the lipid-lowering therapy currently available. In fact, with current treatments (statins, ezetimibe and PCSK9 inhibitors), the majority of patients in secondary prevention should achieve low-density lipoprotein cholesterol goals. For these reasons, in this manuscript promoted by the Spanish Society of Cardiology we propose three simple and feasible decision-making algorithms that include the majority of clinical scenarios among patients with ischemic heart disease, with the double aim of attaining therapeutic goals in the majority of patients as soon as possible; in secondary prevention the magnitude of the benefit is risk- and time-dependent.

Glucagon circulates in concentrations in the low picomolar range, which is demanding regarding the sensitivity of the methods for quantification applied. In addition, the differential and tissue specific proteolytic processing of the glucagon precursor and the presence in of several glucagon-like sequences, not only in the precursor of glucagon, but also in a number of other peptides of the glucagon-secretin family of peptides, put special demands on the specificity of the assays. Finally, experience has shown that unspecific interference of plasma components has presented additional problems. All of these problems have resulted in a lot of diverging results concerning measured and reported glucagon responses in both humans and experimental animals that have and still are causing considerable debate and controversy. There is very solid evidence that glucagon is an important hormone in human and mammalian metabolism, but its precise physiological role in glucose and lipid metabolism and in metabolic disease has been difficult to establish, not least because of these difficulties. It was our purpose with this review to discuss the methods of glucagon quantification and discuss pitfalls and sources of error. We also reviewed some of the dogmas regarding glucagon secretion in the light of the methodological difficulties.

Over the last decade, finding bacterial strains with ability to accumulate high concentrations of lipids has gained increasing interest, since these lipids may be used in different industries. Here we describe two methods for evaluation of lipid accumulation in cyanobacteria, following by our personal reflection on issues surrounding the use of these methods. First, we present the Bligh and Dyer protocol as a traditional extraction method using organic solvents for quantitative determination of lipids and next Nile red, a selective fluorescent stain, that has been used as a rapid approach for both qualitative and quantitative measurement of lipids.