Number Of Lipid Droplets Research Articles

Effects of quercetin and hydroxytyrosol supplementation in a high-fat diet on growth, lipid metabolism, and mitochondrial function in spotted seabass (Lateolabrax maculatus)

Endoplasmic reticulum (ER) stress and mitochondrial impairment commonly occur during the progression of fatty liver disease. There is a close connection and crosstalk between mitochondria and ER. The potential positive influence of mitigating ER stress (ERS) and mitochondrial damage in the context of preventing and treating fatty liver was explored in spotted seabass (Lateolabrax maculatus) as a susceptible model to fatty liver. A normal-fat diet (11% fat, NFD) and a high-fat diet (17% fat, HFD) were formulated and three additional diets were prepared by supplementation of quercetin (QUE) (0.1%), hydroxytyrosol (HT) (0.02%) or their combination (0.1% QUE + 0.02% HT) to the HFD (HFD + QUE HFD + HT and HFD + QUE + HT diets).Three replicate groups of fish (25 ± 0.02 g) were fed the test diets to visual satiety for 8 weeks. The results revealed the deterioration of growth, feed intake and feed utilization in HFD group compared to the NFD group whereas QUE and HT application improved their values and the optimum results were achieved for the HFD + QUE + HT group. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and both serum and hepatic triglyceride (TG), total cholesterol (T-CHO) and non-esterified free fatty acids (NEFA) concentrations were enhanced in HFD group, and their values decreased by QUE and HT, particularly their combined supplementation. The results of oil red O staining exhibited a remarkable reduction in number of lipid droplets in the liver of fish from HFD + QUE + HT group compared to the HFD group. Whole-body and muscle fat contents and abdominal fat index decreased by QUE and HT application. Expression of lipid metabolism related genes (srebp-1c, fas, acc) were down-regulated by QUE and HT treatment. Co-supplementation of QUE and HT down-regulated the expression of ERS-related genes (grp78, chop, perk, atf6, ire1), improved ER ultrastructure, and enhanced the coupling between mitochondria and ER. Moreover, expression of genes associated with hepatic mitochondrial biogenesis (pgc1-α, pgc1-β, nrf1) and mitophagy (pink1, atg5, mul1) was up-regulated in HFD + QUE, HFD + HT and HFD + QUE + HT groups. These data suggest that combined supplementation of QUE and HT in HFD for spotted seabass can improve growth and feed utilization, reduce hepatic damage and fat accumulation, and alleviate HFD induced ERS and mitochondrial dysfunction.

Lipid droplets synthesized during luteinization are degraded after pregnancy.

After pregnancy, the corpus luteum (CL) functions as a transient endocrine gland that produces progesterone, which is necessary to maintain pregnancy. To maintain constant progesterone production, CLs are enriched in lipids as its precursors. Lipid droplets (LDs) are organelles that originate from the endoplasmic reticulum and store neutral lipids such as triacylglycerols and cholesteryl esters. The size and number of LDs in a cell are regulated by LD-associated proteins that coat their surface. LD degradation is regulated by either neutral lipid hydrolases (lipolysis), selective autophagic mechanism (lipophagy), or both. Mammalian CLs are long known to be enriched in LDs, but LDs are rapidly depleted after pregnancy and reappear near the time of delivery. In this present study, we hypothesized that LDs synthesized by luteinization are massively degraded after pregnancy. Using mCherry-HPos mice, in which LD synthesis can be visualized in vivo, we found that LD synthesis, which was activated during luteal development, was suppressed after implantation. In CLs, LD synthesis remained low during pregnancy, but was reactivated before and after delivery. These changes in LDs were confirmed using electron microscopy and immunostaining. Furthermore, LD degradation was mediated by lipolysis rather than lipophagy. In summary, our findings indicate that luteinization-induced LD synthesis is suppressed after pregnancy onset and that CLs are lipid-poor during pregnancy because LDs stored during luteal development are extensively degraded by lipolysis.

Lipid-lowering and antioxidant effects of Polygonatum fermented liquor: a study on intestinal microbiota and brain-gut axis in mice.

This study aims to investigate the effects of Polygonatum fermented liquor (PFL) on improving lipid metabolism and oxidative stress in mice by regulating the gut microbiota. Forty SPF-grade male Kunming mice were randomly divided into four groups: normal control group (NC), general liquor group (GC), fresh Polygonatum fermented liquor group (FPC), and nine-steam-nine-bask Polygonatum fermented liquor group (NPC). Each group was administered with sterile water, general liquor, fresh Polygonatum fermented liquor, and nine-steam-nine-bask Polygonatum fermented liquor, respectively, by gavage. The mice's liver, brain tissue, serum, and intestinal contents were collected. The indicators of oxidative stress in the liver, four blood lipid indicators, gamma-aminobutyric acid (GABA), and brain-derived neurotrophic factor (BDNF) levels in the brain tissue were measured, liver hematoxylin and eosin (HE) staining was performed, and the gut microbiota in the small intestine were analyzed using 16S rRNA second-generation sequencing technology. Compared with the NC group, the NPC group showed significantly increased liver glutathione peroxidase (GSH-Px) content in mice (p < 0.05), reduced number of lipid droplets in the liver cells, and increased GABA and BDNF content in the brain tissues. The NPC group regulated lipid metabolism by lowering low-density lipoprotein cholesterol (LDL-C) and increasing high-density lipoprotein cholesterol (HDL-C) content in the mouse serum. Gut microbiota analysis showed significant changes in the gut microbiota of mice in the FPC and NPC groups, with increased richness and species diversity. These two groups increased the abundance of beneficial bacteria such as Lactobacillus, unclassified Muribaculaceae, unclassified Bacilli, and uncultured Bacteroidales bacterium while reducing the abundance of harmful bacteria such as Candidatus Arthromitus, and Staphylococcus, with a particularly significant reduction in Staphylococcus (p < 0.05). It is speculated that the two types of PFL may exert lipid-lowering and antioxidant effects by modulating the abundance of these dominant bacteria. Further studies showed that various environmental factors are closely related to the dominant gut bacteria. Malondialdehyde (MDA) was significantly negatively correlated with Lactobacillus and unclassified Bacilli, superoxide dismutase (SOD) was significantly negatively correlated with Staphylococcus (p < 0.01) and significantly negatively correlated with Candidatus Arthromitus (p < 0.05), and HDL-C was significantly negatively correlated with Staphylococcus and Facklamia (p < 0.05). The two types of PFL chosen in this study may exert lipid-lowering and antioxidant effects by modulating the composition and function of the gut microbiota, providing guidance for the industrial application of Polygonatum.

Effects of Curcumin on the Egg Quality and Hepatic Lipid Metabolism of Laying Hens.

Curcumin, the major active compound of turmeric, has shown potential benefits for poultry health and production in various studies. However, its specific role in enhancing the egg quality and liver health of laying hens, as well as its underlying mechanisms, have yet to be determined. Here, a total of 600 Su Qin No.1 Laying hens, aged 55 weeks and with similar laying rates, were randomly placed into five groups, with 10 replicates of 12 hens each. Curcumin doses of 0, 100, 200, 400, and 800 mg/kg were added to the basal diet to form the experimental groups. After an 8-week feeding period, no significant changes were observed in the production performance of laying hens due to curcumin supplementation. However, additional tests revealed that a 200 mg/kg curcumin supplementation improved albumen height, yolk color, Haugh unit, and eggshell thickness, while reducing the thin albumen's weight and proportion. This was accompanied by a significant down-regulation of the mRNA expression level of the Prolactin Receptor (Prlr) in the oviduct magnum. Furthermore, the number of hepatic lipid droplets and the hepatic triglyceride (TG) content, as well as malondialdehyde (MDA) levels were significantly reduced, indicating improved hepatic lipid metabolism and oxidative status. This was accompanied by a significant reduction in the expressions of sterol regulatory element binding protein-1 gene (Srebp-1), fatty acid synthase gene (Fasn), as well as fatty acid synthase (FASN), which are closely related to fatty acid synthesis in the liver. Overall, these findings suggest that curcumin supplementation at a dosage of 200 mg/kg could lead to significant improvements in egg quality and hepatic lipid metabolism.

Adjusting function of camphor on primary metabolism in Cinnamomum camphora stressed by high temperature

Cinnamomum camphora has great economic value for its wide utilization in traditional medicine and furniture material, and releases lots of monoterpenes to tolerate high temperature. To uncover the adjusting function of monoterpenes on primary metabolism and promoting their utilization as anti-high temperature agents, the photosynthetic capacities, primary metabolite levels, cell ultrastructure and associated gene expression were surveyed in C. camphora when it was blocked monoterpene biosynthesis with fosmidomycin (Fos) and fumigated with camphor (a typical monoterpene in the plant) under high temperature (Fos+38 °C+camphor). Compared with the control (28 °C), high temperature at 38 °C decreased the starch content and starch grain size, and increased the fructose, glucose, sucrose and soluble sugar content. Meanwhile, high temperature also raised the lipid content, with the increase of lipid droplet size and numbers. These variations were further intensified in Fos+ 38 °C treatment. Compared with Fos+ 38 °C treatment, Fos+ 38 °C+camphor treatment improved the starch accumulation by promoting 4 gene expression in starch biosynthesis, and lowered the sugar content by suppressing 3 gene expression in pentose phosphate pathway and promoting 15 gene expression in glycolysis and tricarboxylic acid cycle. Meanwhile, Fos+ 38 °C+camphor treatment also lowered the lipid content, which may be caused by the down-regulation of 2 genes in fatty acid formation and up-regulation of 4 genes in fatty acid decomposition. Although Fos+ 38 °C+camphor treatment improved the photosynthetic capacities in contrast to Fos+ 38 °C treatment, it cannot explain the variations of these primary metabolite levels. Therefore, camphor should adjust related gene expression to maintain the primary metabolism in C. camphora tolerating high temperature.

Antidiabetic property of fractions and pure compounds from Andrographis paniculata

Chlorophyll-free fractions of Andrographis paniculata were investigated for glucose uptake and lipid reduction in 3T3-L1 adipocytes. At 25 µg/ml, the acid fraction concentration enhanced glucose uptake by 82%. Basic and neutral fractions at 100 µg/ml enhanced glucose uptake by 82% and 78%, respectively. The three fractions showed improved glucose uptake compared to the crude extract (25% uptake at 50 μg/ml). GC-MS analysis of the fractions revealed the presence of chemicals with antidiabetic activities. The neutral fraction was prioritised for pure compound isolation to provide known andrographolide (1), 14-deoxyandrographolide (2), and a novel compound, 3-epi-11,12-didehydro-14-deoxyandrographolide (5). At a concentration of 1 µM, compounds 2 and 5 are as effective as 10 mM metformin in glucose uptake. They also reduce lipid accumulations in 3T3-L1 adipocytes by decreasing the size and number of lipid droplets. The activities of fractions and compounds support the use of A. paniculata in treating type 2 diabetes.

Qa-SNARE syntaxin 18 mediates lipid droplet fusion with SNAP23 and SEC22B

Lipid droplets (LDs) are dynamic lipid storage organelles that can sense and respond to changes in systemic energy balance. The size and number of LDs are controlled by complex and delicate mechanisms, among which, whether and which SNARE proteins mediate LD fusion, and the mechanisms governing this process remain poorly understood. Here we identified a SNARE complex, syntaxin 18 (STX18)–SNAP23–SEC22B, that is recruited to LDs to mediate LD fusion. STX18 targets LDs with its transmembrane domain spanning the phospholipid monolayer twice. STX18–SNAP23–SEC22B complex drives LD fusion in adiposome lipid mixing and content mixing in vitro assays. CIDEC/FSP27 directly binds STX18, SEC22B, and SNAP23, and promotes the lipid mixing of SNAREs-reconstituted adiposomes by promoting LD clustering. Knockdown of STX18 in mouse liver via AAV resulted in smaller liver and reduced LD size under high-fat diet conditions. All these results demonstrate a critical role of the SNARE complex STX18–SNAP23–SEC22B in LD fusion.

Simvastatin’s Mitochondrial Defenses against Angiotensin II-Induced Heart Failure

Background and Aims: Heart failure is one cardiovascular condition that might progress due to mitochondrial dysfunction. In chronic heart failure, 3hydroxy-3-methylglutaryl CoA reductase inhibitors (statins), which prevent the production of ROS, have cardioprotective benefits. However, it is still unknown how statins can protect the mitochondria in heart failure Experimental Strategy: Angiotensin II (1.5 mg/kg/day) or co-administered simvastatin (oral, 10 mg/kg/day) were given to rats for 14 days, after which the treatment was withdrawn. Wheat germ agglutinin staining and echocardiography were used to analyze the structure and function of the heart. Transmission electron microscopy was used to analyze the shape of the mitochondria as well as the numbers of lipid droplets, lysosomes, autophagosomes, and mitophagosomes. After stimulating human cardiomyocytes, flow cytometry was used to assess changes in intracellular ROS and mitochondrial membrane potential (m). and, respectively, JC1 staining. By using immunohistochemistry and western blotting, apoptotic proteins that are associated to autophagy, mitophagy, and mitochondrial regulation were identified. Key outcomes Simvastatin mitigated the disruption of m and dramatically decreased ROS generation. Simvastatin stimulated autophagy and mitophagy, caused lipid droplets to accumulate, and provided energy for maintaining mitochondrial function and impeded apoptosis that was mediated by mitochondria. According to these results, simvastatin-mediated mitochondrial protection prevents heart failure by modifying antioxidant status and enhancing energy sources for autophagy and mitophagy, which prevent mitochondrial damage and cardiomyocyte apoptosis. Final Thoughts and Implications Mitochondria are crucial in controlling the course of heart failure. Simvastatin reduced angiotensin II-induced heart failure through mitochondrial preservation and may offer a new treatment for heart failure prevention.

Vitamin D modulates disordered lipid metabolism in zebrafish (Danio rerio) liver caused by exposure to polystyrene nanoplastics

In this study, zebrafish (Danio rerio) were exposed to polystyrene nanoplastics (PS-NPs, 80 nm) at 0, 15, or 150 μg/L for 21 days and supplied with a low or high vitamin D (VD) diet (280 or 2800 IU/kg, respectively, indicated by – or +) to determine whether and how VD can regulate lipid metabolism disorder induced by PS-NPs. Six groups were created according to the PS-NP concentration and VD diet status: 0−, 0+, 15−, 15+,150−, and 150 +. Transmission electron microscopy showed that PS-NPs accumulated in the livers of zebrafish, which led to large numbers of vacuoles and lipid droplets in liver cell matrices; this accumulation was most prominent in the 150− group, wherein the number of lipid droplets increased significantly by 136.36%. However, the number of lipid droplets decreased significantly by 76.92% in the 150+ group compared with the 150− group. An examination of additional biochemical indicators showed that the high VD diet partially reversed the increases in the triglyceride and total cholesterol contents induced by PS-NPs (e.g., triglycerides decreased by 58.52% in the 150+ group, and total cholesterol decreased by 44.64% in the 15+ group), and regulated lipid metabolism disorder mainly by inhibiting lipid biosynthesis. Untargeted lipidomics analysis showed that exposure to PS-NPs was associated mainly with changes in the lipid molecular content related to cell membrane function and lipid biosynthesis and that the high VD diet reduced the content of lipid molecules related to lipid biosynthesis, effectively alleviating cell membrane damage and lipid accumulation. These findings highlight the potential of VD to alleviate lipid metabolism disorder caused by PS-NP exposure, thereby providing new insights into how the toxic effects of NPs on aquatic organisms could be reduced.

Rational design fluorescent dyes based on morpholine derivatives for specific imaging of lysosomes and lipid droplets in living cells

Lysosomes and lipid droplets (LDs), as two crucial sub-organelles within cells, play a pivotal role in maintaining the normal cellular functions. However, rational design and synthesis of fluorophores that selectively target specific organelles still pose a challenge. Herein, we developed a series of eight fluorescent dyes (LCA1-LCA4 and LCN1-LCN4) containing morpholine moiety, which effectively targeting lysosome and LDs within cells through rational regulation of substituents in the molecular structure. Among these compounds, compounds LCA1/LCN1 containing triphenylamine group and LCA3/LCN4 containing coumarin group exhibit specific targeting towards the LDs, whereas compound LCN2 containing carbazole group demonstrates targeted localization to lysosome. Moreover, these five compounds displayed the advantages of high cellular viability, excellent resistance to interference, pH insensitivity and the ability to enter cells without washing. Compounds LCN2 and LCA1 are capable of real-time monitoring the dynamic behavior of lysosome and LDs respectively, as well as the mitophagy (LCN2) or the number and diameter variations of LDs (LCA1). The results provide a potential candidate for specific lysosomes and LDs imaging.

Elucidating the functional role of human ABHD16B lipase in regulating triacylglycerol mobilization and membrane lipid synthesis in Saccharomyces cerevisiae

Lipids are essential biological macromolecules that play a pivotal role in various physiological processes and cellular homeostasis. ABHD16B, a member of the α/β-hydrolase domain (ABHD) superfamily protein, has emerged as a potential key regulator in lipid metabolism. However, the precise role of human ABHD16B in lipid metabolism remains unclear. In this study, we reported the overexpression of ABHD16B in Saccharomyces cerevisiae to determine its physiological relevance in lipid metabolism. Through in vivo [14C]acetate labeling experiments, we observed that overexpression of ABHD16B causes a decrease in cellular triacylglycerol (TAG) levels and a concurrent increase in phospholipid synthesis in wild-type cells. Mass spectrometry (LC–MS/MS) analysis further corroborated these findings, showing a significant decrease in TAGs with a carbon chain length of 48 and an increase in major phospholipid species, specifically 34:2, upon overexpression of ABHD16B. Confocal microscopy analysis revealed a reduction in the number of lipid droplets in strains overexpressing ABHD16B, consistent with the observed decrease in neutral lipids. Additionally, qRT-PCR analysis indicated a high phospholipid synthetic activity of ABHD16B and a potential decrease in TAG levels in wild-type yeast, possibly due to upregulation of endogenous TAG hydrolytic enzymes, as confirmed using 3tglsΔ mutant strain. Furthermore, GC-MS analysis revealed significant modifications in fatty acid composition upon ABHD16B overexpression. Collectively, our results underscore the influence of ABHD16B overexpression on TAG levels, phospholipid synthesis, lipid droplet dynamics, and fatty acid composition. These findings reveal a complex interplay between TAG hydrolysis and phospholipid synthesis, highlighting the critical involvement of ABHD16B in lipid homeostasis and providing further insights into its regulatory function in cellular lipid metabolism.

Effects of partial replacement of fish meal with black soldier fly (Hermetia illucens) larvae meal on growth performance, lipid metabolism and hepatointestinal health of juvenile golden pompano (Trachinotus ovatus)

This experiment was conducted to investigate the effects of partial replacement of fish meal with black soldier fly larvae (BSFL) meal on growth performance, body and muscle nutrients, lipid metabolism, intestinal morphology and microbiota of juvenile golden pompano (Trachinotus ovatus). Three isolipidic (12.40 ± 0.29%) and isoproteinic (42.98 ± 0.02%) experimental diets were formulated to feed golden pompano by replacing 0% (BSFL0), 25% (BSFL25) and 50% (BSFL50) of fish meal with BSFL meal. The experiment lasted for a total of 8 weeks. The results showed that compared with BSFL0, BSFL25 could significantly increase feed intake of golden pompano (P < 0.05). However, BSFL50 significantly reduced growth performance (P < 0.05). The hepatosomatic index, body and muscle crude fat in BSFL25 and BSFL50 decreased. BSFL25 could significantly reduce the activity of fatty acid synthase (FAS) and significantly enhance the activity of lipase (LPS) (P < 0.05). Both BSFL25 and BSFL50 could significantly reduce the number and volume of lipid droplets in the liver, but BSFL50 could damage the intestinal morphology and shorten the intestinal villi. Compared with BSFL0, the richness (Chao1, ACE, Sobs) and diversity (Shannon and Simpson) of intestinal microbiota in BSFL25 and BSFL50 were increased, and the abundance of Proteobacteria, Actinobacteria and Bacteroidetes was increased. In conclusion, the replacement of 25% fish meal in the feed by BSFL meal improved the food intake, lipid deposition in the liver, and intestinal microbiota balance of golden pompano, and had no harmful effects on growth and intestinal health. However, when the substitution level reached 50%, it would have a negative impact on growth and intestinal health.

Medium Depth Influences O2 Availability and Metabolism in Human RPE Cultures.

Retinal pigment epithelium (RPE) oxidative metabolism is critical for normal retinal function and is often studied in cell culture systems. Here, we show that conventional culture media volumes dramatically impact O2 availability, limiting oxidative metabolism. We suggest optimal conditions to ensure cultured RPE is in a normoxic environment permissive to oxidative metabolism. We altered the availability of O2 to human primary and induced pluripotent stem cell-derived RPE cultures directly via a hypoxia chamber or indirectly via the amount of medium over cells. We measured oxygen consumption rates (OCRs), glucose consumption, lactate production, 13C6-glucose and 13C5-glutamine flux, hypoxia inducible factor 1α (HIF-1α) stability, intracellular lipid droplets after a lipid challenge, transepithelial electrical resistance, cell morphology, and pigmentation. Medium volumes commonly employed during RPE culture limit diffusion of O2 to cells, triggering hypoxia, activating HIF-1α, limiting OCR, and dramatically altering cell metabolism, with only minor effects on typical markers of RPE health. Media volume effects on O2 availability decrease acetyl-CoA utilization, increase glycolysis and reductive carboxylation, and alter the size and number of intracellular lipid droplets under lipid-rich conditions. Despite having little impact on visible and typical markers of RPE culture health, media volume dramatically affects RPE physiology "under the hood." As RPE-centric diseases like age-related macular degeneration involve oxidative metabolism, RPE cultures need to be optimized to study such diseases. We provide guidelines for optimal RPE culture volumes that balance ample nutrient availability from larger media volumes with adequate O2 availability seen with smaller media volumes.

Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome.

Irisin is a thermogenic hormone that leads to causes energy expenditure by increasing brown adipose tissue (BAT). This protein hormone that enables the conversion of white adipose tissue (WAT) to BAT is the irisin protein. This causes energy expenditure during conversion. WAT stores triglycerides and fatty acids and contains very few mitochondria. They also involve in the development of insulin resistance (IR). WAT, which contains a very small amount of mitochondria, contributes to the formation of IR by storing triglycerides and fatty acids. WAT functions as endocrine tissue in the body, synthesizing various molecules such as leptin, ghrelin, NUCB2/nesfatin-1, and irisin along with fat storage. BAT is quite effective in energy expenditure, unlike WAT. The number of mitochondria and lipid droplets composed of multicellular cells in BAT is much higher when compared to WAT. BAT contains a protein called uncoupling protein-1 (UCP1) in the mitochondrial membranes. This protein pumps protons from the intermembrane space toward the mitochondrial matrix. When UCP1 is activated, heat dissipation occurs while ATP synthesis does not occur, because UCP1 is a division protein. At the same time, BAT regulates body temperature in infants. Its effectiveness in adults became clear after the discovery of irisin. The molecular mechanism of exercise, which increases calorie expenditure, became clear with the discovery of irisin. Thus, the isolation of irisin led to the clarification of metabolic events and fat metabolism. In this review, literature information will be given on the effect of irisin hormone on energy metabolism and metabolic syndrome (MetS).

Ketogenic diet alleviates β-cell dedifferentiation but aggravates hepatic lipid accumulation in db/db mice

ObjectiveThe aim of this study was to explore the effect of the ketogenic diet (KD) on β-cell dedifferentiation and hepatic lipid accumulation in db/db mice. MethodsAfter a 3-wk habituation, male db/db mice ages 8 wk were assigned into one of three groups: normal diet (ND), KD, and 75% calorie restriction (CR) group. Free access to a standard diet, a KD, and 75% of a standard diet, respectively, were given to each group. Additionally, sex-matched 8-wk-old C57BL/6 mice were used to construct a control (C) group. After a 4-wk dietary intervention, mouse body weight, fasting blood glucose (FBG), blood lipids, fasting insulin (FINS), glucose tolerance, and β-hydroxybutyric acid level were measured. The morphologies of the islet and liver were observed by hematoxylin and eosin staining. Positive expressions of β-cell–specific transcription factors in mouse islets were determined by double immunofluorescence staining. The size and number of lipid droplets in mouse liver were examined by Oil Red O staining. Real-time quantitative reverse transcription polymerase chain reaction detected relative levels of adipogenesis-associated and lipolysis-associated genes in mouse liver. Additionally, expressions of CD36 protein in the mouse liver were determined by immunohistochemical staining and Western blot. ResultsAfter a 4-wk dietary intervention, FBG, FINS, and glucose area under the curve in the KD group became significantly lower than in the ND group (all P < 0.05). Regular morphology of mouse islets was observed in the KD group, with an increased number of islet cells. The KD significantly reversed the decrease in β-cell number, disarrangement of β-cells, decline of β/α-cell ratio, and downregulation of β-cell–specific transcription factors in db/db mice. Serum levels of triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol were comparable between the ND and KD groups. In contrast, serum triacylglycerol levels were significantly lower in the CR group than in the ND group (P < 0.05). Vacuolar degeneration and lipid accumulation in the liver were more prominent in the KD group than in the ND and CR groups. The mRNA levels of Pparα and Acox1 in the KD group were lower than those in the ND group, although no significant differences were detected. Relative levels of Cd36 and inflammatory genes in the mouse liver were significantly higher in the KD group than in the ND group (all P < 0.05). ConclusionThe KD significantly reduced FBG and FINS and improved glucose tolerance in db/db mice by upregulating β-cell–specific transcription factors and reversing β-cell dedifferentiation. However, the KD also induced hepatic lipid accumulation and aggravated inflammatory response in the liver of db/db mice.

Exogenous H2 S promotes ubiquitin-mediated degradation of SREBP1 to alleviate diabetic cardiomyopathy via SYVN1 S-sulfhydration.

Diabetic cardiomyopathy, a distinctive complication of diabetes mellitus, has been correlated with the presence of intracellular lipid deposits. However, the intricate molecular mechanisms governing the aberrant accumulation of lipid droplets within cardiomyocytes remain to be comprehensively elucidated. Both obese diabetic (db/db) mice and HL-1 cells treated with 200μmol/L palmitate and 200μmol/L oleate were used to simulate type 2 diabetes conditions. Transmission electron microscopy is employed to assess the size and quantity of lipid droplets in the mouse hearts. Transcriptomics analysis was utilized to interrogate mRNA levels. Lipidomics and ubiquitinomics were employed to explore the lipid composition alterations and proteins participating in ubiquitin-mediated degradation in mice. Clinical data were collected from patients with diabetes-associated cardiomyopathy and healthy controls. Western blot analysis was conducted to assess the levels of proteins linked to lipid metabolism, and the biotin-switch assay was employed to quantify protein cysteine S-sulfhydration levels. The administration of H2 S donor, NaHS, effectively restored hydrogen sulfide levels in both the cardiac tissue and plasma of db/db mice (+7%, P<0.001; +5%, P<0.001). Both db/db mice (+210%, P<0.001) and diabetic patients (+83%, P=0.22, n=5) exhibit elevated plasma triglyceride levels. Treatment with GYY4137 effectively lowers triglyceride levels in db/db mice (-43%, P=0.007). The expression of cystathionine gamma-lyase and HMG-CoA reductase degradation protein 1 (SYVN1) was decreased in db/db mice compared with the wild-type mice (cystathionine gamma-lyase: -31%, P=0.0240; SYVN1: -35%, P=0.01), and NaHS-treated mice (SYVN1: -31%, P=0.03). Conversely, the expression of sterol regulatory element-binding protein 1 (SREBP1) was elevated (+91%, P=0.007; +51%, P=0.03 compared with control and NaHS-treated mice, respectively), along with diacylglycerol O-acyltransferase 1 (DGAT1) (+95%, P=0.001; +35%, P=0.02) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) (+88%, P=0.01; +22%, P=0.32). Exogenous H2 S led to a reduction in lipid droplet formation (-48%, P<0.001), restoration of SYVN1 expression, modification of SYVN1's S-sulfhydration status and enhancement of SREBP1 ubiquitination. Overexpression of SYVN1 mutated at Cys115 decreased SREBP1 ubiquitination and increased the number of lipid droplets. Exogenous H2 S enhances ubiquitin-proteasome degradation of SREBP1 and reduces its nuclear translocation by modulating SYVN1's cysteine S-sulfhydration. This pathway limits lipid droplet buildup in cardiac myocytes, ameliorating diabetic cardiomyopathy.

Chlorogenic Acid from Burdock Roots Ameliorates Oleic Acid-Induced Steatosis in HepG2 Cells through AMPK/ACC/CPT-1 Pathway.

Hepatic steatosis can cause liver dysfunction and cell injury, on which natural functional factors are expected to be an effective approach for long-term intervention. However, the cellular molecular mechanisms are unclear. Chlorogenic acid is a phenolic compound, which can regulate lipid metabolism and is abundant in burdock root. The aim of this study was to investigate the potential molecular mechanism of the effect of chlorogenic acid from burdock root (ACQA) on steatosis in HepG2 cells. In this study, we found that ACQA reduced the number of lipid droplets and lipid levels in oleic acid-treated HepG2 cells. Molecular mechanistic results showed that ACQA enhanced CPT-1 expression by activating AMPK-related signaling pathways, and the concentrations of Ca2+ and cAMP were increased with the intervention of ACQA. In addition, ACQA enhanced the β-oxidation of fatty acids, reduced alanine transaminase and aspartate transaminase, and inhibited apoptosis in oleic acid-treated HepG2 cells. Our studies elucidate a novel mechanism that ACQA enhances the β-oxidation of fatty acids through the AMPK/ACC/CPT-1 pathway to protect against steatosis in HepG2 cells, which provides insight into its molecular mechanism as well as intervention strategies for chlorogenic acid against fatty liver diseases.

Lycopene Alleviates the Adverse Effects of Feeding High-Lipid Diets to Hybrid Grouper (♀Epinephelus fuscoguttatus ×♂E. lanceolatus).

It has been found that high-lipid diets (HLDs) disrupt lipid metabolism in fish, leading to an excessive accumulation of lipids in various tissues of the fish body. The objective of this study was to investigate if the inclusion of lycopene (LCP) in an HLD may mitigate the adverse consequences of excessive dietary lipid intake in hybrid grouper (♀ Epinephelus fuscoguttatus × ♂ E. lanceolatus). The experimental design incorporated a control group (L0), which was administered a diet consisting of 42% protein and 16% lipid. The diets for groups L1, L2, and L3 were developed by augmenting the control diet with 100, 200, and 400 mg/kg LCP, respectively. The duration of the trial spanned a period of 42 days. The results of the study showed that the weight gain rate (WGR) and protein efficiency ratio (PER) of the three LCP treatment groups (L1, L2, and L3) tended to increase and then decrease, with a significant increase in WGR and PER in L2 (P < 0.05). Visceral somatic index and hepatic somatic index tended to decrease and then increase in all treatment groups, with a significant decrease in L2 (P < 0.05). In serum dietary LCP significantly reduced triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) content and significantly increased high-density lipoprotein (HDL) content (P < 0.05). In the liver, dietary LCP reduced TC, TG, and very LDL levels and improved lipoprotein lipase, hepatic lipase, fatty acid (FA) synthetase, and acetyl-CoA carboxylase activities. The number and area of hepatic lipid droplets decreased significantly with increasing LCP content. In the liver, the addition of appropriate levels of LCP significantly upregulated lipoprotein lipase (lpl) and peroxisome proliferator-activated receptor α (pparα). In summary, dietary LCP improves growth and reduces lipid deposition in the liver of hybrid grouper by increasing lipolytic metabolism and decreasing FA synthesis. Under the experimental conditions, the fitted curve analysis showed that the recommended LCP additions to the high lipid diet for juvenile hybrid grouper were 200-300 mg/kg.

Harnessing polarity-dependent fluorescent probe for lipid droplet metabolism dissection and in vivo nonalcoholic fatty liver disease diagnosis

Nonalcoholic fatty liver disease (NAFLD) has emerged as a prevalent chronic liver condition worldwide. The dysregulated metabolism of lipid droplets (LDs) in cells is physiologically and pathologically linked to NAFLD. The development of fluorescent probes for imaging LD metabolism holds promise for noninvasive diagnosis and understanding of NAFLD. However, the development of such probes is challenging, and their in vivo diagnostic potential remains largely unexplored. Here, we present the synthesis of ZP-1, a bright fluorophore serving as a specific probe for LDs. ZP-1 possesses a donor-acceptor electronic structure with intramolecular charge transfer characteristics and shows polarity-dependent emission. In highly polar solvents, such as water, ZP-1 exhibits minimal fluorescence, while in low-polarity solvents, it displays strong fluorescence. This property enables high-specificity LD detection with excellent imaging contrast. Attributed to its high photostability and pH stability, ZP-1 effectively visualizes LD metabolism in live cells via real-time imaging, encompassing processes such as growth, migration, fusion, and fission. Moreover, we demonstrate in vivo diagnosis of NAFLD in a mouse model, providing rich information regarding LD morphology, numbers, volumes, and tissue structures. This work introduces ZP-1 as a valuable tool for NAFLD diagnosis and research, facilitating noninvasive assessment and improved understanding of the disease.

A stable NIR fluorescent probe for imaging lipid droplets in triple-negative breast cancer

Lipid droplets (LDs) are closely associated various diseases, such as liver diseases and cancers. In the last decade, a mountain of fluorescent probes has been developed for LDs, while the ones bearing near-infrared (NIR) emission, superb specificity, and high stability are still lacking. In this work, we prepare a phenothiazine-derived probe that shows a suitable hydrophobicity with ClogP as 6.25 and a strong emission at 681 nm in the low polarity solvents such as 1,4-dioxane, enabling the NIR imaging of LDs. The probe is verified to showcase high chemostability, superb pH tolerance, and excellent anti-photobleaching capacity. Using the probe, the changes in the polarity, size, and number of LDs can be monitored in living cells under different stimuli. Moreover, a variety of morphological dynamics of LDs is visualized over a period of time, including fusion, fission, transfer of lipid, LD growth, and lipolysis. Utilizing its NIR feature, in vivo tumor imaging is achieved and the therapeutic efficacy of cisplatin is primarily assessed in a triple-negative breast cancer mice model using LDs as the biomarker for the first time. These results suggest that NIR-LD is potential to act as a potent imaging agent for LDs-related diseases.