Anh The Nguyen, Masashi Masuda, Yuki Mori, Yuichiro Adachi, Teppei Fukuda, Airi Furuichi, Masaki Takikawa, Yuki Tsuda, Yuki Hamada, Yusuke Maruyama, Hirokazu Ohminami, Kohta Ohnishi, Yutaka Taketani
All-trans retinoic acid (atRA), a metabolite of vitamin A, reduces hepatic lipid accumulation in liver steatosis model animals. Lipophagy, a new lipolysis pathway, degrades a lipid droplet (LD) via autophagy in adipose tissue and the liver. We recently found that atRA induces lipophagy in adipocytes. However, it remains unclear whether atRA induces lipophagy in hepatocytes. In this study, we investigated the effects of atRA on lipophagy in Hepa1c1c7 cells and the liver of mice fed a high-fat diet (HFD). Firstly, we confirmed that atRA induced autophagy in Hepa1c1c7 cells by Western blotting and the GFP-LC3-mCherry probe...
July 18, 2024: Journal of Lipid Research
Patcharamon Seubnooch, Matteo Montani, Jean-Francois Dufour, Mojgan Masoodi
Alteration in lipid metabolism plays a pivotal role in developing metabolic dysfunction-associated steatohepatitis (MASH). However, our understanding of alteration in lipid metabolism across liver zonation in MASH remains limited. Within this study, we investigated MASH-associated zone-specific lipid metabolism in a diet and chemical-induced MASH mouse model. Spatial lipidomics using mass spectrometry imaging in a MASH mouse model revealed 130 lipids from various classes altered across liver zonation and exhibited zone-specific lipid signatures in MASH...
July 18, 2024: Journal of Lipid Research
Qiyao Zhu, Sijia Wang, Gang Fu, Fengming Guo, Wei Huang, Tengyue Zhang, Huina Dong, Zhaoxia Jin, Dawei Zhang
Lipophilic compounds have a variety of positive effects on human physiological functions and exhibit good effects in the prevention and treatment of clinical diseases. This has led to significant interest in the technical applications of synthetic biology for the production of lipophilic compounds. However, the strict selective permeability of the cell membrane and the hydrophobic nature of lipophilic compounds pose significant challenges for their production. During fermentation, lipophilic compounds tend to accumulate within cell membrane compartments rather than being secreted extracellularly...
July 17, 2024: Journal of Lipid Research
Bence Cs Szabo, Mate Szabo, Peter Nagy, Zoltan Varga, Gyorgy Panyi, Tamas Kovacs, Florina Zakany
Membrane lipids extensively modulate the activation gating of voltage-gated potassium channels (KV ), however, much less is known about mechanisms of ceramide and glucosylceramide actions including which structural element is the main intramolecular target and whether there is any contribution of indirect, membrane biophysics-related mechanisms to their actions. We used two-electrode voltage-clamp fluorometry capable of recording currents and fluorescence signals to simultaneously monitor movements of the pore domain (PD) and the voltage sensor domain (VSD) of the KV 1...
July 15, 2024: Journal of Lipid Research
Ying Feng, Shan Luo, Chen Fang, Shinan Ma, Dandan Fan, Yanghui Chen, Zhuo Chen, Xiang Zheng, Yijun Tang, Xiaobei Duan, Xingling Liu, Xuzhi Ruan, Xingrong Guo
Liver injury is closely related to poor outcomes in sepsis patients. Current studies indicate that sepsis is accompanied by metabolic disorders, especially those related to lipid metabolism. It is highly important to explore the mechanism of abnormal liver lipid metabolism during sepsis. As a key regulator of glucose and lipid metabolism, angiopoietin-like 8 (ANGPTL8) is involved in the regulation of multiple chronic metabolic diseases. In the present study, severe liver lipid deposition and lipid peroxidation were observed in the early stages of lipopolysaccharide (LPS) induced liver injury...
July 15, 2024: Journal of Lipid Research
Begoña Porteiro, Reinout L P Roscam Abbing, Wietse In Het Panhuis, Dirk R de Waart, Suzanne Duijst, Isabelle Bolt, Esther W Vogels, Johannes H M Levels, Laura A Bosmans, Winnie G Vos, Ronald P J Oude Elferink, Esther Lutgens, Stan F J van de Graaf
Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na+ taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models...
July 13, 2024: Journal of Lipid Research
Lihong Teng, Nikolaos Dedousis, Aneseh Adeshirlarijaney, Jitendra S Kanshana, Min Liu, Craig A Hodges, Alison B Kohan
Intestinal disease is one of the earliest manifestations of cystic fibrosis (CF) in children and is closely tied to deficits in growth and nutrition, both of which are directly linked to future mortality. Patients are treated aggressively with pancreatic enzyme replacement therapy and a high-fat diet to circumvent fat malabsorption, but this does not reverse growth and nutritional defects. We hypothesized that defects in chylomicron production could explain why CF body weights and nutrition are so resistant to clinical treatments...
July 12, 2024: Journal of Lipid Research
Kenneth R Feingold, Peter M Elias
No abstract text is available yet for this article.
July 11, 2024: Journal of Lipid Research
Penny M Kris-Etherton, Terrence M Riley, Kristina S Petersen
No abstract text is available yet for this article.
July 10, 2024: Journal of Lipid Research
Jannik Rousel, Catherine Mergen, Menthe E Bergmans, Lisa J Bruijnincx, Marieke L de Kam, Naomi B Klarenbeek, Tessa Niemeyer-van der Kolk, Martijn B A van Doorn, Joke A Bouwstra, Robert Rissmann
INTRODUCTION: The epidermal inflammation associated with psoriasis drives skin barrier perturbations. The skin barrier is primarily located in stratum corneum (SC). Its function depends on the SC lipid matrix of which ceramides constitute important components. Changes in the ceramide profile directly correlate to barrier function. In this study, we characterized the dynamics of the barrier function and ceramide profile of psoriatic skin during anti-Interleukin-23 therapy with guselkumab...
July 9, 2024: Journal of Lipid Research
Xiangyun Sun, Qinghong Yu, Yifei Qi, Bilian Kang, Xinyan Zhao, Lin Liu, Ping Wang, Min Cong, Tianhui Liu
Mitochondria can contact lipid droplets (LDs) to form peridroplet mitochondria (PDM) which trap fatty acids in LDs by providing ATP for triglyceride synthesis, and prevent lipotoxicity. However, the role of PDM in metabolic dysfunction associated steatotic liver disease (MASLD) is not clear. Here, the features of PDM in dietary MASLD models with different severity in mice were explored. Electron microscope photographs show that LDs and mitochondria rarely come into contact with each other in normal liver. In mice fed with high-fat diet, PDM can be observed in the liver as early as the beginning of steatosis in hepatocytes...
July 7, 2024: Journal of Lipid Research
Hayley G Law, Kimber L Stanhope, Wei Zhang, Munkhtuya Myagmarsuren, Zahraa M Jamshed, Muhammad A Khan, Heejung Bang, Peter J Havel, Lars Berglund, Byambaa Enkhmaa
Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. A size polymorphism in the apolipoprotein(a) [apo(a)] gene, determined by the number of Kringle (K) repeats, inversely regulates Lp(a) levels. Non-genetic factors including dietary saturated fat influence Lp(a) levels. However, less is known about the effects of carbohydrates including dietary sugars. In this double-blind, parallel-arm study among 32 overweight/obese adults, we investigated the effect of consuming glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks on Lp(a) level and assessed the role of the apo(a) size polymorphism...
July 3, 2024: Journal of Lipid Research
Frieda Bardey, Lorenz Rieck, Dominik Spira, Winfried März, Priska Binner, Stefanie Schwab, Marcus E Kleber, Magdalena Danyel, Rasmus Barkowski, Thomas Bobbert, Joachim Spranger, Elisabeth Steinhagen-Thiessen, Ilja Demuth, Ursula Kassner
BACKGROUND: Severe hypertriglyceridemia (HTG) has predominantly multifactorial causes (MCS). Yet a small subset of patients have the monogenetic form (FCS). It remains a challenge to distinguish patients clinically, since decompensated MCS might mimic FCS´s severity. Aim of the current study was to determine clinical criteria that could sufficiently distinguish both forms as well as to apply the FCS score proposed by Moulin and colleagues. METHODS: We retrospectively studied 72 patients who presented with severe HTG in our clinic during a time span of seven years and received genetic testing...
July 3, 2024: Journal of Lipid Research
Yadi Tang, Mariola Majewska, Britta Leß, Ilir Mehmeti, Philipp Wollnitzke, Nina Semleit, Bodo Levkau, Julie D Saba, Gerhild van Echten-Deckert, Ewa Gurgul-Convey
Lipotoxicity has been considered the main cause of pancreatic beta-cell failure during type 2 diabetes development. Lipid droplets (LD) are believed to regulate the beta-cell sensitivity to free fatty acids (FFA), but the underlying molecular mechanisms are largely unclear. Accumulating evidence points, however, to an important role of intracellular sphingosine-1-phosphate (S1P) metabolism in lipotoxicity-mediated disturbances of beta-cell function. In the present study, we compared the effects of an increased irreversible S1P degradation (S1P-lyase, SPL overexpression) with those associated with an enhanced S1P recycling (overexpression of S1P phosphatase 1, SGPP1) on LD formation and lipotoxicity in rat INS1E beta-cells...
June 29, 2024: Journal of Lipid Research
Tiffany R Bellomo, Yuxi Liu, Thomas C Gilliland, Hannah Miksenas, Sara Haidermota, Megan Wong, Xingdi Hu, Joaquim Rosado Cristino, Auris Browne, Jorge Plutzky, Sotirios Tsimikas, James L Januzzi, Pradeep Natarajan
The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPL) in the development and progression of coronary disease is known, but their influence on extra-coronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extra-coronary vascular disease and incident major adverse limb events (MALE). 446 participants who underwent coronary and/or peripheral angiography were followed up for a median of 3...
June 26, 2024: Journal of Lipid Research
José de Jesús Flores-Sierra, Magaly Del Rosario Muciño-Arellano, Gloria Del Carmen Romo-Morales, Jaime Eduardo Sánchez-Palafox, Viridiana Abigail Correa-Navarro, Dannia Colín-Castelán, Victoriano Pérez-Vázquez, Rubén Rangel-Salazar, Rafael Rivera-Bustamante, Carmen de la Rocha, Dalia Rodríguez-Ríos, Diana Lilia Trejo-Saavedra, Jorge Molina-Torres, Enrique Ramírez-Chávez, Nancy Shyrley García-Rojas, Robert Winkler, Gertrud Lund, Silvio Zaina
Increasing evidence hints that DNA hypermethylation may mediate the pathogenic response to cardiovascular risk factors. Here, we tested a corollary of that hypothesis, i.e., that the DNA methyltransferase inhibitor decitabine (Dec) ameliorates the metabolic profile of mice fed a moderately high-animal fat and protein diet (HAFPD), a proxy of cardiovascular risk-associated Western-type diet. HAFPD-fed mice were exposed to Dec or vehicle for eight weeks (8W set, 4-32/group). To assess any memory of past exposure to Dec, we surveyed a second mice set treated as 8W but HAFPD-fed for further eight weeks without any Dec (16W set, 4-20/group)...
June 26, 2024: Journal of Lipid Research
Allen H Lee, Justin M Snider, Sitapriya Moorthi, Nicolas Coant, Magali Trayssac, Daniel Canals, Christopher J Clarke, Chiara Luberto, Yusuf A Hannun
Measurements of sphingolipid metabolism are most accurately performed by liquid chromatography-mass spectrometry. However, this technique is expensive, not widely accessible, and without the use of specific probes, it does not provide insight into metabolic flux through the pathway. Employing the fluorescent ceramide analogue NBD-C6 -ceramide as a tracer in intact cells, we developed a comprehensive HPLC-based method that simultaneously measures the main nodes of ceramide metabolism in the Golgi. Hence, by quantifying the conversion of NBD-C6 -Ceramide to NBD-C6 -sphingomyelin, NBD-C6 -Hexosylceramides, and NBD-C6 -ceramide-1-phosphate (NBD-C1P), the activities of Golgi resident enzymes sphingomyelin synthase 1, glucosylceramide synthase, and ceramide kinase (CERK) could be measured simultaneously...
June 24, 2024: Journal of Lipid Research
Derek Besch, Drew R Seeger, Brennon Schofield, Svetlana A Golovko, Meredith Parmer, Mikhail Y Golovko
Dramatic post-mortem prostanoid (PG) enzymatic synthesis in the brain causes a significant artifact during PG analysis. Thus, enzyme deactivation is required for an accurate in situ endogenous PG quantification. To date, the only method for preventing post-mortem brain PG increase with tissue structure preservation is fixation by head-focused microwave irradiation (MW), which is considered the gold standard method, allowing for rapid in situ heat-denaturation of enzymes. However, MW requires costly equipment that suffers in reproducibility, causing tissue loss and metabolite degradation if overheated...
June 21, 2024: Journal of Lipid Research
Jeyanthini Risikesan, Sara Heebøll, Indumathi Kumarathas, Esben Søndergaard, Rakel F Johansen, Steffen Ringgaard, Niels K Aagaard, Thomas D Sandahl, Gerda E Villadsen, Lars C Gormsen, Jan Frystyk, Michael D Jensen, Henning Grønbæk, Søren Nielsen
This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis vs. steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [3 H]palmitate and [14 C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions...
June 18, 2024: Journal of Lipid Research
Yanni Xiong, Jie Luo, Zi-Yun Hong, Wen-Zhuo Zhu, Ao Hu, Bao-Liang Song
Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells...
June 14, 2024: Journal of Lipid Research
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