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Phospholipase A2 group VI (PLA2G6, also called iPLA2β) has been implicated in male fertility, neuronal disorders, and metabolic diseases. However, its therapeutic effects on metabolic disorders remain elusive. We investigated the effects of PLA2G6 suppression on glucose and lipid metabolism. Systemic inhibition of PLA2G6 in high-fat diet-fed mice reduced hepatic lipid droplet size without altering the levels of serum triglycerides and fasting blood glucose. Suppression of liver-specific Pla2g6 utilizing the short-hairpin RNA knockdown technique using an adenovirus vector (Ad-shPLA2G6) altered phospholipid and fatty acid metabolites and suppressed hepatic lipid accumulation, serum triglyceride, fasting glucose, and insulin levels. Additionally, Ad-shPLA2G6 treatment downregulated lipid biosynthesis-related genes but upregulated peroxisomal fatty acid oxidation-related genes. These findings indicate that targeting hepatic Pla2g6 modulates phospholipid and fatty acid metabolites and improves glucose and lipid metabolism, suggesting Pla2g6 as a potential therapeutic target in metabolic disorders, including type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease.
ABSTRACT Invasive species pose a significant threat to ecosystems worldwide. To support effective management, it is crucial to clarify their distribution ranges and dispersal processes. Here, we applied an environmental DNA (eDNA)‐based mitochondrial DNA haplotyping approach to invasive black bass species to characterize their invasion ranges and haplotype compositions, thereby inferring their dispersal processes. We conducted a nationwide eDNA survey focusing on three established species in Japan, i.e., Northern largemouth bass (Micropterus nigricans), Florida largemouth bass (M. salmoides), and Smallmouth bass (M. dolomieu). Our survey detected eDNA of at least one species at 87 of 121 sites, recovered most previously reported haplotypes, and showed strong concordance with capture‐based data, demonstrating high sensitivity and accuracy. The haplotyping data revealed contrasting patterns among the three species. Northern largemouth bass, first introduced in 1925, is now widespread, with haplotype distribution suggesting gradual, localized geographic expansion across most regions. However, the high haplotype diversity observed on Shikoku Island, one of Japan's major islands, despite invasion only after 1972, suggests extensive human‐mediated translocations. Florida largemouth bass, introduced in 1988, was restricted to western Japan, with no signal of stepwise expansion, implying strong effects of human‐mediated translocations. Smallmouth bass, a more recent invader, was broadly distributed with only two haplotypes detected; eDNA results closely matched recent governmental survey data on invasion fronts. Our findings highlight the influence of differing invasion histories and the ongoing role of human intervention in bass dispersal. This study demonstrates that the eDNA haplotyping enables broad‐scale rapid monitoring while also providing insight into translocations and dispersal through population genetic structure, thereby facilitating efforts to prevent further invasions.
Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse event caused by drugs such as bortezomib, vincristine, paclitaxel, and oxaliplatin (L-OHP). This condition can lead to the discontinuation of anticancer drug administration and a diminished quality of life, posing a significant clinical problem. However, the only currently recognized effective treatment is duloxetine, and new therapeutic options are urgently required. Lentinula edodes mycelia extract (LEM) has been reported to improve CIPN in mouse models and alleviate numbness in patients with persistent neuropathy following L-OHP treatment. However, the active ingredients responsible for the attenuation of neuropathy remain unknown. We extracted the fractions from LEM, and an L-OHP-evoked allodynia mouse model was used to investigate which fraction contained the active ingredient. LEM was separated into an ethanol-soluble fraction (LES), an ethanol-insoluble fraction (LEP), and LEM(-), a hot water extract from the LEM-free medium. LEP abolished L-OHP-evoked allodynia, whereas LES and LEM(-) did not. In addition, fractionation of LEP based on molecular weight sieving yielded fractions LEP-1 (molecular weight ≥ 100,000) and LEP-2 (molecular weight < 100,000), the latter of which was found to inhibit L-OHP-evoked allodynia. Similarly, fractionation of LEP-2 gave rise to LEP-3 (molecular weight 3500-50,000) and LEP-4 (molecular weight ≤ 3500), the former of which had no inhibitory effects on L-OHP-evoked allodynia, whereas an inhibitory effect was observed in response to the administration of LEP-4. In addition, LEP-4 was found to abrogate the expression of NR2A and Cav3.2 mRNAs in the dorsal root ganglion (DRG), and inhibited the activation of extracellular regulated-protein kinase 1/2 (ERK1/2) in both the spinal cord and DRG. Moreover, oral administration of 0.25 g/kg LEP-4 ameliorated allodynia, which had developed following L-OHP administration. These findings indicate that the active component preventing CIPN in LEM resides in LEP-4. This compound has prophylactic and therapeutic potential for L-OHP-evoked allodynia by abrogating NR2A and Cav3.2 mRNA expression and activating ERK1/2.
The incidence of type 2 diabetes mellitus (T2DM) has been increasing worldwide. In the pathophysiology of metabolic diseases, including T2DM, both the quantity and quality of lipids that accumulate in the body have attracted significant research attention. Excess lipids accumulate in non-adipose tissues, such as the liver and skeletal muscles, leading to insulin resistance and an increased risk of developing T2DM. The liver is the central organ for glucose and lipid metabolism, and impaired hepatic regulatory mechanisms lead to hyperglycemia, insulin resistance, and hepatic lipid accumulation. Hepatic triglyceride (TG) accumulation contributes to the development of hepatic insulin resistance; however, the quantity of TGs alone is insufficient to explain the development of glucose and lipid metabolic dysfunctions. Thus, we focus on lipid quality, particularly fatty acids. In addition to TGs, phospholipids store fatty acids, which vary in carbon chain length, number of double bonds, and position of double bonds (such as ω3 and ω6), resulting in lipid diversity. Changes in the fatty acid chains of phospholipids are also strongly associated with glucose and lipid metabolism. In this mini review, we discuss the involvement of hepatic lipid quantity and quality in T2DM, with the aim of contributing to the development of novel T2DM therapies.
The search for Architecture in “Function” or “Art” relations has consistently evolved since the modern and postmodern eras, driven by rapid technological and material advancements. This research examines the relationship between architectural expression and the concept of “Function or Art.” The literature review method was used in this research, which involved taking case studies of buildings. This research found that “Function and Art are manifest simultaneously.” This research aims to guide the design of buildings that utilize Architecture that is “Function”, “Art”, or “Function and Art”, all of which express architectural works in accordance with the desired design idea. The implications of this research are for practitioners and theorists to consider the “Function or Art” of the selected building expressions.
