Three members of CIDE proteins play important roles in several aspects of lipid metabolism through different tissue distribution, cellular localization, and interacting proteins. We review the molecular and cellular mechanisms of CIDE proteins in controlling lipid droplet fusion and lipid storage, promoting lipid secretion, and regulating activities of transcriptional factors.

The cell death-inducing DFF45-like effector (CIDE) proteins, including Cidea, Cideb, and Cidec/Fsp27, regulate various aspects of lipid homeostasis, including lipid storage, lipolysis, and lipid secretion. This review focuses on the physiological roles of CIDE proteins based on studies on knockout mouse models and human patients bearing CIDE mutations. The primary cellular function of CIDE proteins is to localize to lipid droplets (LDs) and to control LD fusion and growth across different cell types. We propose a four-step process of LD fusion, characterized by (a) the recruitment of CIDE proteins to the LD surface and CIDE movement, (b) the enrichment and condensate formation of CIDE proteins to form LD fusion plates at LD–LD contact sites, (c) lipid transfer through lipid-permeable passageways within the fusion plates, and (d) the completion of LD fusion. Lastly, we outline CIDE-interacting proteins as regulatory factors, as well as their contribution in LD fusion.

Seipin is a key factor in the assembly of lipid droplets at the endoplasmic reticulum. Here, we review recent advances provided by structural, biochemical, and in silico analyses that provided mechanistic insights into seipin function in lipid droplet formation.

Lipid droplets (LDs) are dynamic organelles essential for cellular lipid homeostasis. Assembly of LDs occurs in the endoplasmic reticulum (ER), and the conserved ER membrane protein seipin emerged as a key player in this process. Here, we review recent advances provided by structural, biochemical, and in silico analysis that revealed mechanistic insights into the molecular role of the seipin complexes and led to an updated model for LD biogenesis. We further discuss how other ER components cooperate with seipin during LD biogenesis. Understanding the molecular mechanisms underlying seipin-mediated LD assembly is important to uncover the fundamental aspects of lipid homeostasis and organelle biogenesis and to provide hints on the pathogenesis of lipid storage disorders.

The accumulation of lipid droplets (LDs) is increasingly recognized as a new hallmark of cancer. In this review, we unravel the role of LDs and three major classes of LD-resident proteins—perilipins, lipases, and acyl-CoA synthetases—in providing metabolic flexibility to cancer cells which enable them to proliferate, invade, metastasize, defy hypoxia, and upsurge their stemness capacity.

A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid-derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD-resident proteins (perilipins, lipases, and acyl-CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.

Age is a risk factor to the onset and progression of hypertension, though adherence to plant-based diets improves blood pressure. Herein, we propose the potential of food (poly)phenols to fluidify cholesterol-rich endothelial membranes and improve the diffusion of nitric oxide (^·NO) contributing to enhanced bioavailability of vascular ^·NO and the nutritional management of hypertension.

Hypertension is a major contributor to premature death, owing to the associated increased risk of damage to the heart, brain and kidneys. Although hypertension is manageable by medication and lifestyle changes, the risk increases with age. In an increasingly aged society, the incidence of hypertension is escalating, and is expected to increase the prevalence of (cerebro)vascular events and their associated mortality. Adherence to plant-based diets improves blood pressure and vascular markers in individuals with hypertension. Food flavonoids have an inhibitory effect towards angiotensin-converting enzyme (ACE1) and although this effect is greatly diminished upon metabolization, their microbial metabolites have been found to improve endothelial nitric oxide synthase (eNOS) activity. Considering the transmembrane location of ACE1 and eNOS, the ability of (poly)phenols to interact with membrane lipids modulate the cell membrane's biophysical properties and impact on nitric oxide (^·NO) synthesis and bioavailability, remain poorly studied. Herein, we provide an overview of the current knowledge on the lipid remodeling of endothelial membranes with age, its impact on the cell membrane's biophysical properties and ^·NO permeability across the endothelial barrier. We also discuss the potential of (poly)phenols and other plant-based compounds as key players in hypertension management, and address the caveats and challenges in adopted methodologies.