Progress in lipid research最新文献

The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a delicately integrated interface composed of firm, essentially dead corneocytes and a distinctive lipid matrix. Together, the stratum corneum lipid matrix and sebum lipids derived from sebaceous glands give rise to a remarkably complex but quite unique blend of skin surface lipids that demonstrates tremendous heterogeneity and provides the skin with its indispensable protective coating. The stratum corneum lipid matrix is composed primarily of three major lipid classes: ceramides, non-esterified fatty acids and cholesterol, whereas sebum is a waxy mixture predominantly composed of acylglycerols, wax esters, non-esterified fatty acids, squalene, cholesterol and cholesterol esters. The balance of these skin surface lipids in terms of their relative abundance, composition, molecular organisation and dynamics, and their intricate interactions play a crucial role in the maintenance of healthy skin. For that reason, even minuscule alterations in skin surface lipid properties or overall lipid profile have been implicated in the aetiology of many common skin diseases including atopic dermatitis, psoriasis, xerosis, ichthyosis and acne. Novel lipid-based interventions aimed at correcting the skin surface lipid abnormalities have the potential to repair skin barrier integrity and the symptoms associated with such skin diseases, even though the exact mechanisms of lipid restoration remain elusive.

The prevalence of Alzheimer's disease (AD) continues to rise due to the increasing aging population. Among the various genetic factors associated with AD, apolipoprotein E (ApoE), a lipid transporter, stands out as the primary genetic risk factor. Specifically, individuals carrying the ApoE4 allele exhibit a significantly higher risk. However, emerging research indicates that dietary factors play a prominent role in modifying the risk of AD. Docosahexaenoic acid (DHA), a prominent ω-3 fatty acid, has garnered considerable attention for its potential to ameliorate cognitive function. The intricate interplay between DHA and the ApoE genotype within the brain, which may influence DHA's utilization and functionality, warrants further investigation. This review meticulously examines experimental and clinical studies exploring the effects of DHA on cognitive decline. Special emphasis is placed on elucidating the role of ApoE gene polymorphism and the underlying mechanisms are discussed. These studies suggest that early DHA supplementation may confer benefits to cognitively normal older adults carrying the ApoE4 gene. However, once AD develops, ApoE4 non-carriers may experience greater benefits compared to ApoE4 carriers, although the overall effectiveness of DHA supplementation at this stage is limited. Potential mechanisms underlying these differential effects may include accelerated DHA catabolism in ApoE4 carriers, impaired transport across the blood-brain barrier (BBB), and compromised lipidation and circulatory function in ApoE4 carriers. Thus, the supplementation of DHA may represent a potential intervention strategy aimed at compensating for these deficiencies in ApoE4 carriers prior to the onset of AD.

Conjugated linoleic acid (CLA) is a functional food ingredient with prebiotic properties that provides health benefits for various human pathologies and disorders. However, limited natural CLA sources in animals and plants have led microorganisms like Lactobacillus and Bifidobacterium to emerge as new CLA sources. Microbial conversion of linoleic acid to CLA is mediated by linoleic acid isomerase and multicomponent enzymatic systems, with CLA production efficiency dependent on microbial species and strains. Additionally, complex factors like LA concentration, growth status, culture substrates, precursor type, prebiotic additives, and co-cultured microbe identity strongly influence CLA production and isomer composition. This review summarizes advances in the past decade regarding microbial CLA production, including bacteria and fungi. We highlight CLA production and potential regulatory mechanisms and discuss using microorganisms to enhance CLA content and nutritional value of fermented products. We also identify primary microbial CLA production bottlenecks and provide strategies to address these challenges and enhance production through functional gene and enzyme mining and downstream processing. This review aims to provide a reference for microbial CLA production and broaden the understanding of the potential probiotic role of microbial CLA producers.

Recently, omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have gained substantial interest due to their specific structure and biological functions. Humans cannot naturally produce these fatty acids (FAs), making it crucial to obtain them from our diet. This comprehensive review details n-3 LC-PUFAs and their role in promoting and maintaining optimal health. The article thoroughly analyses several sources of n-3 LC-PUFAs and their respective bioavailability, covering marine, microbial and plant-based sources. Furthermore, we provide an in-depth analysis of the biological impacts of n-3 LC-PUFAs on health conditions, with particular emphasis on cardiovascular disease (CVD), gastrointestinal (GI) cancer, diabetes, depression, arthritis, and cognition. In addition, we highlight the significance of fortification and supplementation of n-3 LC-PUFAs in both functional foods and dietary supplements. Additionally, we conducted a detailed analysis of the several kinds of n-3 LC-PUFAs supplements currently available in the market, including an assessment of their recommended intake, safety, and effectiveness. The dietary guidelines associated with n-3 LC-PUFAs are also highlighted, focusing on the significance of maintaining a well-balanced intake of n-3 PUFAs to enhance health benefits. Lastly, we highlight future directions for further research in this area and their potential implications for public health.

MDD (major depressive disorder) is a highly prevalent mental disorder with a complex etiology involving behavioral and neurochemical factors as well as environmental stress. The interindividual variability in response to stress stimuli may be explained by processes such as long-term potentiation (LTP) and long-term depression (LTD). LTP can be described as the strengthening of synaptic transmission, which translates into more efficient cognitive performance and is regulated by brain-derived neurotrophic factor (BDNF), a protein responsible for promoting neural growth. It is found in high concentrations in the hippocampus, a part of the limbic system which is far less active in people with MDD. Omega-3 fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) not only contribute to structural and antioxidative functions but are essential for the maintenance of LTP and stable BDNF levels. This review explores the mechanisms and potential roles of omega-3 fatty acids in the prevention of MDD.

The barrier function of the skin is primarily located in the stratum corneum (SC), the outermost layer of the skin. The SC is composed of dead cells with highly organized lipid lamellae in the intercellular space. As the lipid matrix forms the only continuous pathway, the lipids play an important role in the permeation of compounds through the SC. The main lipid classes are ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs). Analysis of the SC lipid matrix is of crucial importance in understanding the skin barrier function, not only in healthy skin, but also in inflammatory skin diseases with an impaired skin barrier. In this review we provide i) a historical overview of the steps undertaken to obtain information on the lipid composition and organization in SC of healthy skin and inflammatory skin diseases, ii) information on the role CERs, CHOL and FFAs play in the lipid phase behavior of very complex lipid model systems and how this knowledge can be used to understand the deviation in lipid phase behavior in inflammatory skin diseases, iii) knowledge on the role of both, CER subclasses and chain length distribution, on lipid organization and lipid membrane permeability in complex and simple model systems with synthetic CERs, CHOL and FFAs, iv) similarity in lipid phase behavior in SC of different species and complex model systems, and vi) future directions in modulating lipid composition that is expected to improve the skin barrier in inflammatory skin diseases.

The unique biophysical and biochemical properties of lipids render them crucial in most models of the origin of life (OoL). Many studies have attempted to delineate the prebiotic pathways by which lipids were formed, how micelles and vesicles were generated, and how these micelles and vesicles became selectively permeable towards the chemical precursors required to initiate and support biochemistry and inheritance. Our analysis of a number of such studies highlights the extremely narrow and limited range of conditions by which an experiment is considered to have successfully modeled a role for lipids in an OoL experiment. This is in line with a recent proposal that bias is introduced into OoL studies by the extent and the kind of human intervention. It is self-evident that OoL studies can only be performed by human intervention, and we now discuss the possibility that some assumptions and simplifications inherent in such experimental approaches do not permit determination of mechanistic insight into the roles of lipids in the OoL. With these limitations in mind, we suggest that more nuanced experimental approaches than those currently pursued may be required to elucidate the generation and function of lipids, micelles and vesicles in the OoL.

Sphingolipids are essential components of all eukaryotic membranes. The bioactive sphingolipid molecule, Sphingosine 1-Phosphate (S1P), regulates various important biological functions. This review aims to provide a comprehensive overview of the role of S1P signaling pathway in various immune cell functions under different pathophysiological conditions including bacterial and viral infections, autoimmune disorders, inflammation, and cancer. We covered the aspects of S1P pathways in NOD/TLR pathways, bacterial and viral infections, autoimmune disorders, and tumor immunology. This implies that targeting S1P signaling can be used as a strategy to block these pathologies. Our current understanding of targeting various components of S1P signaling for therapeutic purposes and the present status of S1P pathway inhibitors or modulators in disease conditions where the host immune system plays a pivotal role is the primary focus of this review.

Macrophages are essential innate immune cells and form our first line of immune defense. Also known as professional phagocytes, macrophages interact and take up various particles, including lipids. Defective lipid handling can drive excessive lipid accumulation leading to foam cell formation, a key feature of various cardiometabolic conditions such as atherosclerosis, non-alcoholic fatty liver disease, and obesity. At the same time, intracellular lipid storage and foam cell formation can also be viewed as a protective and anti-lipotoxic mechanism against a lipid-rich environment and associated elevated lipid uptake. Traditionally, foam cell formation has primarily been linked to cholesterol uptake via native and modified low-density lipoproteins. However, other lipids, including non-esterified fatty acids and triacylglycerol (TAG)-rich lipoproteins (very low-density lipoproteins and chylomicrons), can also interact with macrophages. Recent studies have identified multiple pathways mediating TAG uptake and processing by macrophages, including endocytosis and receptor/transporter-mediated internalization and transport. This review will present the current knowledge of how macrophages take up different lipids and lipoprotein particles and address how TAG-rich lipoproteins are processed intracellularly. Understanding how macrophages take up and process different lipid species such as TAG is necessary to design future therapeutic interventions to correct excessive lipid accumulation and associated co-morbidities.

Dysregulation of fatty acid metabolism and de novo lipogenesis is a key driver of several cancer types through highly unsaturated fatty acid (HUFA) signaling precursors such as arachidonic acid. The human chromosome 11q13 locus has long been established as the most frequently amplified in a variety of human cancers. The fatty acid desaturase genes (FADS1, FADS2 and FADS3) responsible for HUFA biosynthesis localize to the 11q12-13.1 region. FADS2 activity is promiscuous, catalyzing biosynthesis of several unsaturated fatty acids by Δ6, Δ8, and Δ4 desaturation. Our main aim here is to review known and putative consequences of FADS2 dysregulation due to effects on the 11q13 locus potentially driving various cancer types. FADS2 silencing causes synthesis of sciadonic acid (5Z,11Z,14Z-20:3) in MCF7 cells and breast cancer in vivo. 5Z,11Z,14Z-20:3 is structurally identical to arachidonic acid (5Z,8Z,11Z,14Z–20:4) except it lacks the internal Δ8 double bond required for prostaglandin and leukotriene synthesis, among other eicosanoids. Palmitic acid has substrate specificity for both SCD and FADS2. Melanoma, prostate, liver and lung cancer cells insensitive to SCD inhibition show increased FADS2 activity and sapienic acid biosynthesis. Elevated serum mead acid levels found in hepatocellular carcinoma patients suggest an unsatisfied demand for arachidonic acid. FADS2 circular RNAs are at high levels in colorectal and lung cancer tissues. FADS2 circular RNAs are associated with shorter overall survival in colorectal cancer patients. The evidence thusfar supports an effort for future research on the role of FADS2 as a tumor suppressor in a range of neoplastic disorders.