Lipids play important roles in energy metabolism along with diverse aspects of biological membrane structure, signaling and other functions. Perturbations of lipid metabolism are responsible for the development of various pathologies comprising metabolic syndrome, obesity, and type 2 diabetes. Accumulating evidence suggests that circadian oscillators, operative in most cells of our body, coordinate temporal aspects of lipid homeostasis. In this review we summarize current knowledge on the circadian regulation of lipid digestion, absorption, transportation, biosynthesis, catabolism, and storage. Specifically, we focus on the molecular interactions between functional clockwork and biosynthetic pathways of major lipid classes comprising cholesterol, fatty acids, triacylglycerols, glycerophospholipids, glycosphingolipids, and sphingomyelins. A growing body of epidemiological studies associate a socially imposed circadian misalignment common in modern society with growing incidence of metabolic disorders, however the disruption of lipid metabolism rhythms in this connection has only been recently revealed. Here, we highlight recent studies that unravel the mechanistic link between intracellular molecular clocks, lipid homeostasis and development of metabolic diseases based on animal models of clock disruption and on innovative translational studies in humans. We also discuss the perspectives of manipulating circadian oscillators as a potentially powerful approach for preventing and managing metabolic disorders in human patients.
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http://dx.doi.org/10.1016/j.plipres.2023.101235 | DOI Listing |
Proc Natl Acad Sci U S A
January 2025
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Nephrology Department, Changzhou Traditional Chinese Medicine Hospital, Changzhou City, China.
To evaluate the effectiveness and feasibility of the copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy program by comparing and analyzing the improvement of blood pressure, blood lipids and blood glucose in hypertensive patients who received copper bianstone scraping combined with Chinese modified termination hypertension dietary therapy intervention. We selected 160 cases of hypertensive patients from July 2022 to March 2024 for the study. They were divided into 80 cases in the comparison group and 80 cases in the observation group according to whether or not they underwent copper bianstone scraping combined with Chinese modified dietary therapy for termination of hypertension.
View Article and Find Full Text PDFSci Adv
January 2025
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
The infiltration and excessive polarization of M1 macrophages contribute to the induction and persistence of low-grade inflammation in joint-related degenerative diseases such as osteoarthritis (OA). The lipid metabolism dysregulation promotes M1 macrophage polarization by coordinating the compensatory pathways of the inflammatory and oxidative stress responses. Here, a self-assembling, licofelone-loaded nanoparticle (termed LCF-CSBN), comprising chondroitin sulfate and bilirubin joined by an ethylenediamine linker, is developed to selectively reprogram lipid metabolism in macrophage activation.
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