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Results for “Lipid Droplets”

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At least 19 recordsLinked to original sources
PubMed2025

The Myo2 adaptor Ldm1 and its receptor Ldo16 mediate actin-dependent lipid droplet motility.

Organelle motility enables strategic cellular reorganizations. In yeast, this process depends on the actin cytoskeleton, type V myosin motor proteins, and organelle-specific myosin adaptor proteins. While the myosin adaptors for most organelles are known, the coupling of myosin to lipid droplets (LDs), the cellular lipid storage organelles, remained enigmatic. Using genome-wide screening, we identified Ldm1 (lipid droplet motility 1/Yer085c) as a myosin adaptor. Ldm1 binds to the globular tail domain of the myosin Myo2 and to the LD surface protein Ldo16 to enable actin-dependent LD motility. Ldo16 has additional roles in LD contact sites to the vacuole and the endoplasmic reticulum, suggesting a coordination of LD motility and organelle tethering. Ldm1 has a second role in mitochondrial transport, and elevated Ldm1 levels rescue defects of the mitochondrial Myo2-adaptors Mmr1/Ypt11. Our work identifies the molecular machinery for LD motility and contributes to a comprehensive understanding of acto-myosin-based cellular reorganization.

Lipid Droplets↗
PubMed1975

Acute effects of ACTH on dissociated adrenocortical cells: quantitative changes in mitochondria and lipid droplets.

To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical denisty of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adedquate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase inmitochondrial volume.

Adrenal Cortex↗
PubMed1979

Studies on intrarenal prostaglandins. Effect of unilateral renal artery constriction on lipid droplets in the medullary interstitial cells of the 'opposite' kidney in rabbits.

The unilateral renal artery in rabbits was constricted, and lipid droplet count in the medullary interstitial cells of the 'opposite' kidney was performed 1 week after surgery. Lipid droplet count in hypertensive rabbits was less than that in both nonhypertensive and normal rabbits and was inversely proportional to the mean blood pressure. Lipid droplet count was significantly correlated with the juxtaglomerular granulation index and the sodium content in the inner medulla. The present results suggest that, in the opposite kidney of rabbits hypertensive due to unilateral constriction of the renal artery, the enhanced release of prostaglandins and the washout of solute in the renal medulla may be induced as a response to increased perfusion pressure and elevated circulating angiotensin.

Animals↗
PubMed1975

Lipid droplet accumulation in cardiac muscle cells of the bat: potential auto-toxicity of the cardiac sympathetic innervation.

The previously described ability of reserpine and parachlorophenylalanine to induce the accumulation of lipid droplets in ventricular cardiac muscle cells of the bat was investigated. Lipid droplet accumulation was assessed qualitatively by light microscopy and quantitatively by morphometric analysis of electron micrographs. An hypothesis that the action of the drugs was an indirect one, mediated by the cardiac adrenergic innervation, was framed and tested. Lipid droplet accumulation occurred during a time of intense sympathetic activity, that of arousal from hibernation. The ability of the two drugs to produce the effect was antagonized by prior sympathetectomy with 6-hydroxy-dopamine. The effect was mimicked by administration of exogenous norepinephrine together with inhibitors of its catabolic enzymes, monoamine oxidase and catechol-o-methyl transferase. These observations are all consistent with the initial hypothesis and raise the possibility that endogenous norepinephrine in the cardiac sympathetic innervation might be, at least potentially, auto-toxic.

Animals↗
PubMed2026

A Phosphoproteomic Platform Identifies Erythrocyte Membrane Protein Band 4.1-Like 3-Mediated Lipid Droplet Remodeling Linked to Liver Cancer Invasion and Migration.

Aberrant lipid metabolism is a hallmark of hepatocellular carcinoma (HCC), yet the regulatory mechanisms governing lipid droplet (LD) dynamics and their contribution to tumor progression remain poorly understood. Here, we developed an ultrasensitive phosphoproteomic platform using high-affinity HPDA@Ti4+ nanospheres to map LD-associated phosphorylation events across six HCC cell lines. By correlating phosphoproteomic signatures with LD morphology, we identified distinct regulatory signatures associated with LD size and abundance. Functional perturbation screens identified two distinct phosphoprotein modules controlling LD size: silencing SH3KBP1, SLK, EHD2, EPB41L3, and NEXN reduced LD size in Huh1 cells, whereas silencing CPD, BET1, UFL1, RRP1B, OGFR, and CD2BP2 enlarged LDs in Huh7 cells. Notably, we identified EPB41L3 as a critical metabolic-metastatic link; its loss decreased LD size and accelerated HCC migration and invasion, correlating with poor clinical prognosis. Crucially, we identified five key phosphorylation sites on EPB41L3 essential for its function; substituting these with alanine completely abolished its regulatory control over both LD size and HCC metastatic potential. Together, these findings delineate a phosphorylation-based regulatory network controlling the LD architecture and metastatic potential in HCC. Our study not only identifies potential therapeutic targets but also establishes a generalizable phosphoproteomic framework for interrogating lipid signaling in cancer metabolism.

Humans↗
PubMed1979

Postnatal changes in the distribution of lipid droplets within the liver lobule of the mouse.

The changes in the distribution of lipid droplets in the liver lobule were studied during the postnatal development of the mouse. At birth, and 1 day after birth, lipid droplets were evenly distributed throughout the lobule. A slightly uneven distribution of the droplets, more in centrilobular areas, appeared 2 days after birth. After this the difference in the number of droplets between the cells of the centrilobular and periportal areas became progressively more marked reaching a maximum by 17 days of age, and then decreasing to the adult level between 21 and 24 days. Thus, heterogeneity among hepatocytes with respect to lipid content is not present in newborn mice but develops gradually during the postnatal development.

Aging↗
PubMed2025

Hepatocyte-specific CLSTN3B ablation impairs lipid droplet maturation and alleviates diet-induced steatohepatitis in mice.

Excessive lipid accumulation in hepatocytes, a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), can lead to progressive liver damage. Understanding the molecular mechanisms governing lipid storage in hepatocytes is essential for identifying therapeutic targets to halt MASLD progression. Here, we show a pivotal role for the protein calsyntenin 3β (CLSTN3B) in promoting lipid droplet (LD) maturation and lipid storage in hepatocytes. Previously characterized as an endoplasmic reticulum (ER)-LD contact protein that facilitates LD maturation in adipocytes, we now show that CLSTN3B expression is strongly induced in mouse hepatocytes by peroxisome proliferator-activated receptor gamma (PPARγ) in response to dietary caloric excess. Hepatocyte-specific deletion of CLSTN3B in mice significantly increases energy expenditure, reduces metabolic efficiency, and protects against diet-induced hepatic steatosis and fibrosis. Mechanistically, CLSTN3B deficiency causes reduced LD phospholipid coverage and increased lipase recruitment. This results in enhanced fatty acid oxidation driven by a futile cycle of lipolysis and re-esterification. Notably, human clinical data reveal a positive correlation between hepatic CLSTN3B expression and MASLD severity and progression, emphasizing its relevance to human disease. Together, our findings establish CLSTN3B as a key regulator of hepatocyte lipid storage and metabolic efficiency and highlight its potential as a therapeutic target in MASLD.

Journal Article↗
PubMed1979

The occurrence of lipid droplets in the proximal and distal tubules of the rat kidney after folic acid treatment.

Folic acid in high doses gives rise to an accumulation of lipid droplets in the kidney in addition to other changes in the epithelial of both proximal and distal tubules. With the administration of methionine a decrease of lipid droplets and an improvement of the structures of most of the membranes and mitochrondria are observed. These findings have been discussed in regard to the theory of the "chemically induced hyperplasia of the kidneys" related to folic acid.

Animals↗
PubMed2026

Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.

Altered microglial lipid metabolism is heavily implicated in Alzheimer's disease (AD) and aging. Recently, protocols were developed to generate human induced pluripotent stem cell-derived microglia-like cells (iMGL) to study microglial function in vitro, including embryoid body-based methods and induced transcription factor (iTF)-dependent approaches. Here, we performed comparative lipidomics on iMGL from these methods and report major differences in multiple lipid classes, including triglycerides (TGs), a storage form of fatty acids implicated in microglial reactivity. TGs are strongly increased in iTF microglia due to the absence of a media supplement (B-27). Supplementing iTF microglia with B-27, or its component L-carnitine, reduces TGs and promotes a homeostatic state. B-27 also renders iTF microglia metabolically responsive to immune stimuli. Overall, our data show that iMGL differentiation methods have a major impact on microglial lipidomes and warrant attention when studying AD and neuroinflammatory processes involving lipids.

Microglia↗
PubMed2025

Plasma membrane accessible cholesterol is regulated by ACC1 and lipid droplets.

Proper maintenance of plasma membrane (PM) cholesterol is essential for diverse processes ranging from animal development to pathogen evasion. Despite decades of study, the mechanisms governing cellular cholesterol regulation are incomplete. Using genome-wide screens we find that ACC1, the rate-limiting enzyme in fatty acid biosynthesis, regulates PM cholesterol transport. ACC1 loss causes a ~10-fold increase in PM accessible cholesterol in cells and mice. Mechanistically, we find that ACC1 regulates lipid droplet (LD) catabolism, and LDs are intimately tied to PM accessible cholesterol levels since reductions or elevations in their numbers block or promote cholesterol trafficking, respectively. Furthermore, LDs are required for cholesterol trafficking induced by 25-hydroxycholesterol, a modulator of inflammation and an interferon-stimulated second messenger that protects cells from pathogen invasion. This work identifies an unrecognized role for ACC1 and LDs in cholesterol regulation, which has implications for diseases where LD numbers are altered, from metabolic syndromes to neurodegeneration.

25-hydroxycholesterol↗
PubMed1979

Unsaturated lipid droplets in liver sinusoids lining cells in a case of Reye-Morgan-Baral syndrome.

The author reports a case of Reye-Morgan-Baral syndrome presenting osmiophilic-dense lipidic bodies in lining cells of hepatic sinusoids. The different lipidic saturation level between the content of these bodies and the one of lipid droplets of hepatocytes could represent a different response, between hepatocytes and lining cells of liver sinusoids, to excessive circulating lipids.

Humans↗
PubMed1976

Lipid droplets of interstitial medullary cells of intact rat kidney with two-kidney Goldblatt hypertension.

Electron microscopic studies have been carried out of the interstitial cells (IC) of the renal medulla in rats with Goldblatt hypertension. Analysis of variance has not revealed any differences in the number of droplets of "unclamped" kidney in the hypertensive rats as compared to the normotensive rats ("resistant" rats, rats with unilateral nephrectomy, and intact rats) at periods from 3 weeks to 1 year. The total volume of the droplets in the IC cytoplasm in hypertensive and intact animals also revealed no difference 3 weeks after the beginning of the experiment. A positive correlation has been found between the number of the droplets and their volume but the low value of the correlation coefficient (r = +0.28) suggests that the number of the droplets cannot be a reliable indicator of the variation of the amount (volume) of thelipid material contained in them. Since it is just the latter parameter that carries the most information for evaluating the content of the droplet material in the IC, preference should be given to calculating the droplet volume rather than counting the number of droplets. The IC in the animals of the experimental groups revealed hypertrophy and hyperlasia of the endoplasmic reticulum and the Golgi complex, which were especially marked at the earlier stages of the experiments.

Animals↗
PubMed2026

Anti-psychotic drugs act synergistically in combination with antifungal drugs to inhibit drug-resistant Cryptococcus neoformans and Candida albicans.

UNLABELLED: Systemic fungal infections cause an estimated 3.8 million deaths annually, approximately 10% of which are caused by drug-resistant infections. With only five classes of antifungal drugs, treatment options are limited. Here, we explore synergistic drug combinations-when the efficacy of two drugs combined is greater than expected based on the sum of each individual drug's efficacy-to improve treatment of drug-resistant Cryptococcus neoformans and Candida albicans. Chlorpromazine acts synergistically with both amphotericin B and fluconazole against multiple fungal species, including azole-resistant C. neoformans and C. albicans. We then performed a genome-wide knockout mutant screen and found that ESCRT pathway mutants are resistant to chlorpromazine, while knockout mutants of genes involved in fatty acid biosynthesis are sensitive. Based on these data, we investigated sterol and fatty acid composition in chlorpromazine-treated cells and found only minor increases in sterol precursors, but a substantial increase in lipid droplet size and decreased lipid droplet numbers. This lipid droplet formation potentially sequesters lipid bioavailability and response to membrane stress. Together, these data suggest that chlorpromazine and its analogs are potentially promising treatments for systemic fungal infections that act via lipid homeostasis and stress response. IMPORTANCE: Fungal infections are a large and expensive health burden with high mortality rates. People with compromised immune systems from cancer, solid organ transplant, HIV infection, and other conditions are particularly affected. Systemic fungal infections are difficult to treat because there are few available drugs and treatment periods last months or years. Long treatment times increase the risk of treatment failure and can contribute to the rise of resistance. We identified an additional class of drugs, chlorpromazine and other phenothiazine drugs, that amplify the activity of existing antifungal drugs amphotericin B (AmB) and fluconazole (FLZ). AmB and FLZ act by targeting ergosterol, the fungal equivalent of cholesterol, which is required for a functional plasma membrane. Chlorpromazine increases the formation of lipid drops, which sequester lipids such as ergosterol. When chlorpromazine is combined with AmB, the fungal cell cannot respond to the plasma membrane damage caused by AmB, inhibiting the fungal cells. This work identifies new target processes and drugs that could treat deadly fungal infections.

antifungal resistance↗
PubMed1977

Effect of zinc deficiency on intestinal transport triglyceride in the rat.

Ultrastructural and biochemical changes in the intestinal epithelium during the process of active triglyceride absorption were studied in rats fed a zinc-deficient diet as compared with those of pair-fed and ad libitum-fed zinc-supplemented controls. The rate of triglyceride absorption markedly decreased in zinc-deficient rats. Despite a significant reduction in pancreatic lipase activity, the digestion of triglycerides proceeded normally in the zinc deficient rats, as evidenced by no apparent signs of diarrhea (or steatorrhea) and by the appearance of the hydrolytic products such as free-fatty acids and monoglycerides in the intestinal mucosa. The mucosa uptake of digested lipids and resynthesis of triglycerides in the mucosa from deficient rats were normal. Ultrastructural and chromatographic analysis of the mucosal lipids indicated a massive accumulation of lipid droplets, predominantly in the form of triglycerides. The primary defect in lipid absorptive processes in zinc-deficient rats occurred in the formation of chylomicrons. The lipid droplets in the mucosa of deficient rats were physically unstable. This instability was shown by coalescence of droplets which did not appear to be membrane-bound. Coalescing lipid droplets ranged from 2.0 to 4.0 micron in diameter. The absorptive cells were not able to discharge lipid droplets of this size into the intercellular spaces and hence into the lamina propria, resulting in the accumulation of the large droplets within the mucosa. This exit block to the movement of lipid droplets out of the mucosal cell appeared to be due to the failure, in zinc-deficiency, of the mucosal synthesis of proteins required for the formation of chylomicrons. Ultrastructural observations demonstrated changes in the subcellular organelles related to protein synthesis, including a marked reduction in granular endoplasmic reticulum and a quiescent appearance of the Golgi-complex.

Animals↗