Sargachromenol Attenuates Inflammatory Responses by Regulating NF-κB and Nrf2 Pathways in RAW 264.7 Cells and LPS-treated Mice.

This study aims to explore the anti-inflammatory mechanisms of sargachromenol in both RAW 264.7 cells and lipopolysaccharide (LPS)-treated mice, as previous reports have suggested that sargachromenol possesses anti-aging, anti-inflammatory, antioxidant, and neuroprotective properties. Although the precise mechanism behind its anti-inflammatory activity remains unclear, pretreatment with sargachromenol effectively reduced the production of nitric oxide, prostaglandin E2, and interleukin (IL)-1ß in LPS-stimulated RAW 264.7 cells by inhibiting cyclooxygenase-2. Moreover, sargachromenol inhibited the activation of nuclear factor-κB (NF-κB) by preventing the degradation of the inhibitor of κB-α (IκB-α) and inhibiting protein kinase B (Akt) phosphorylation in LPS-stimulated cells. We also found that sargachromenol induced the production of heme oxygenase-1 (HO-1) by activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2). In LPS-treated mice, oral administration of sargachromenol effectively reduced the levels of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum, suggesting its ability to suppress the production of inflammatory mediators by inhibiting the Akt/NF-κB pathway and upregulating the Nrf2/HO-1 pathway.

The Role of Macrophage Populations in Skeletal Muscle Insulin Sensitivity: Current Understanding and Implications.

Insulin resistance is a crucial factor in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Skeletal muscle, the body's largest insulin-responsive tissue, plays a significant role in the pathogenesis of T2DM due to defects in insulin signaling. Recently, there has been growing evidence that macrophages, immune cells essential for tissue homeostasis and injury response, also contribute to the development of skeletal muscle insulin resistance. This review aims to summarize the current understanding of the role of macrophages in skeletal muscle insulin resistance. Firstly, it provides an overview of the different macrophage populations present in skeletal muscle and their specific functions in the development of insulin resistance. Secondly, it examines the underlying mechanisms by which macrophages promote or alleviate insulin resistance in skeletal muscle, including inflammation, oxidative stress, and altered metabolism. Lastly, the review discusses potential therapeutic strategies targeting macrophages to improve skeletal muscle insulin sensitivity and metabolic health.

Potential Beneficial Effects of Sargassum spp. in Skin Aging.

Seaweeds are receiving much attention as a rich source of bioactive compounds with cosmeceutical potential. Recent studies have revealed that Sargassum spp., a genus of brown algae in the family Sargassaceae, has multiple functions in preventing and improving skin aging. Sargassum spp. contains many bioactive compounds, such as fucoidan, fucoxanthin, terpenoids, flavonoids, and meroterpenoids. These Sargassum spp. extracts and derivative compounds have excellent potential for skincare, as they exhibit skin health-promoting properties, including antioxidants, anti-inflammation, whitening, skin barrier repair, and moisturizing. Therefore, searching for bioactive compounds in marine resources such as Sargassum spp. could be an attractive approach to preventing and improving skin aging. The current review focused on the various biological abilities of Sargassum extracts or derived compounds for anti-skin aging.

Marine Biological Macromolecules and Chemically Modified Macromolecules; Potential Anticoagulants.

Coagulation is a potential defense mechanism that involves activating a series of zymogens to convert soluble fibrinogen to insoluble fibrin clots to prevent bleeding and hemorrhagic complications. To prevent the extra formation and diffusion of clots, the counterbalance inhibitory mechanism is activated at levels of the coagulation pathway. Contrariwise, this system can evade normal control due to either inherited or acquired defects or aging which leads to unusual clots formation. The abnormal formations and deposition of excess fibrin trigger serious arterial and cardiovascular diseases. Although heparin and heparin-based anticoagulants are a widely prescribed class of anticoagulants, the clinical use of heparin has limitations due to the unpredictable anticoagulation, risk of bleeding, and other complications. Hence, significant interest has been established over the years to investigate alternative therapeutic anticoagulants from natural sources, especially from marine sources with good safety and potency due to their unique chemical structure and biological activity. This review summarizes the coagulation cascade and potential macromolecular anticoagulants derived from marine flora and fauna.

Ribes fasciculatum Ameliorates High-Fat-Diet-Induced Obesity by Elevating Peripheral Thermogenic Signaling.

Ribes fasciculatum has been consumed as a food and as a traditional medicine for treating autoimmune diseases and aging in diverse countries. A previous study showed that a mixture of Ribes fasciculatum and Cornus officinalis prohibited adipocyte differentiation and lipid accumulation in preadipocytes and suppressed diet-induced obesity. Nevertheless, the mechanism of R. fasciculatum to regulate energy homeostasis solely through thermogenic signaling remains unclear. Thus, we investigated its effects on energy homeostasis using R. fasciculatum fed to C57BL/6 mice with a 45% high-fat diet. Chronic consumption of R. fasciculatum decreased the body weight of obese mice with increasing food intakes and improved metabolic-syndrome-related phenotypes. Therefore, we further tested its thermogenic effects. Cold chamber experiments and qPCR studies indicated that R. fasciculatum elevated thermogenic signaling pathways, demonstrated by increased body temperature and uncoupling protein 1 (UCP1) signaling in the white and brown adipose tissues. Afzelin is one major known compound derived from R. fasciculatum. Hence, the isolated compound afzelin was treated with preadipocytes and brown adipocytes for cell viability and luciferase assay, respectively, to further examine its thermogenic effect. The studies showed that the response of afzelin was responsible for cell viability and the increased UCP1. In conclusion, our data indicated that R. fasciculatum elevated peripheral thermogenic signaling through increased UCP1 via afzelin activation and ameliorated diet-induced obesity.

Geraniin Inhibits the Entry of SARS-CoV-2 by Blocking the Interaction between Spike Protein RBD and Human ACE2 Receptor.

The coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the development of vaccines, the emergence of SARS-CoV-2 variants and the absence of effective therapeutics demand the continual investigation of COVID-19. Natural products containing active ingredients may be good therapeutic candidates. Here, we investigated the effectiveness of geraniin, the main ingredient in medical plants Elaeocarpus sylvestris var. ellipticus and Nephelium lappaceum, for treating COVID-19. The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (hACE2) receptor to initiate virus entry into cells; viral entry may be an important target of COVID-19 therapeutics. Geraniin was found to effectively block the binding between the SARS-CoV-2 spike protein and hACE2 receptor in competitive enzyme-linked immunosorbent assay, suggesting that geraniin might inhibit the entry of SARS-CoV-2 into human epithelial cells. Geraniin also demonstrated a high affinity to both proteins despite a relatively lower equilibrium dissociation constant (KD) for the spike protein (0.63 µM) than hACE2 receptor (1.12 µM), according to biolayer interferometry-based analysis. In silico analysis indicated geraniin's interaction with the residues functionally important in the binding between the two proteins. Thus, geraniin is a promising therapeutic agent for COVID-19 by blocking SARS-CoV-2's entry into human cells.

Effects of Sargaquinoic Acid in Sargassum Serratifolium on Inducing Brown Adipocyte-like Phenotype in Mouse Adipocytes In Vitro.

A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of Sargassum serratifolium (MES) stimulated adipose tissue browning and inhibited diet-induced obesity and metabolic syndrome. Sargaquinoic acid (SQA) is a major component in MES. We investigated the effects of SQA on the differentiation of preadipocytes to the beige adipocytes. SQA was treated in 3T3-L1 adipocytes differentiated under a special condition that has been reported to induce the browning of adipocytes. SQA at 10 µM reduced lipid accumulation by approximately 23%. SQA at 2.5 - 10 µM induced the differentiation of white adipocytes to beige adipocytes partially by increasing the mitochondrial density and the expression of beige/brown adipocyte markers. In addition, SQA activated lipid catabolic pathways, evidenced by the increased expression levels of perilipin, carnitine palmitoyltransferase 1, and acyl-CoA synthetase long-chain family member 1. As a partial mechanism, biochemical and in silico analyses indicate that SQA activated AMP-activated protein kinase signaling in adipocytes.

Recent Trends in Controlling the Enzymatic Browning of Fruit and Vegetable Products.

Enzymatic browning because of polyphenol oxidases (PPOs) contributes to the color quality of fruit and vegetable (FV) products. Physical and chemical methods have been developed to inhibit the activity of PPOs, and several synthetic chemical compounds are commonly being used as PPO inhibitors in FV products. Recently, there has been an emphasis on consumer-oriented innovations in the food industry. Consumers tend to urge the use of natural and environment-friendly PPO inhibitors. The purpose of this review is to summarize the mechanisms underlying the anti-browning action of chemical PPO inhibitors and current trends in the research on these inhibitors. Based on their mechanisms of action, chemical inhibitors can be categorized as antioxidants, reducing agents, chelating agents, acidulants, and/or mixed-type PPO inhibitors. Here, we focused on the food ingredients, dietary components, food by-products, and waste associated with anti-browning activity.

Novel SIRT1 activator MHY2233 improves glucose tolerance and reduces hepatic lipid accumulation in db/db mice.

The NAD+-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720. We performed an in vitro SIRT1 activity assay to identify the strongest SIRT1 activator. The assay confirmed MHY2233 to be the strongest SIRT1 activator (1.5-fold more potent than resveratrol), and docking simulation showed that the binding affinity of MHY2233 was higher than that of resveratrol and SRT1720. To investigate its beneficial effects, db/db mice were orally administered MHY2233 for 1 month, and various metabolic parameters were assessed in the serum and liver tissues. MHY2233 markedly ameliorated insulin signaling without affecting body weight in db/db mice. In particular, the mRNA expression of lipogenic genes, such as acetyl CoA carboxylase, fatty acid synthase, and sterol regulatory element-binding protein, which increased in db/db mice, decreased following oral treatment with MHY2233. In conclusion, the novel SIRT1 activator MHY2233 reduced lipid accumulation and improved insulin resistance. This finding may contribute toward therapeutic approaches for fatty liver disease and glucose tolerance.

A PPAR Pan Agonist, MHY2013 Alleviates Age-Related Hepatic Lipid Accumulation by Promoting Fatty Acid Oxidation and Suppressing Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, including carnitine palmitoyltransferase 1 (CPT1) and peroxisomal acyl-CoA oxidase 1 (ACOX1), without apparent change in the mRNA expression of lipogenesis-related genes. Furthermore, MHY2013 significantly increased systemic fibroblast growth factor 21 (FGF21) and adiponectin levels and suppressed inflammatory mRNA expression in the liver. In conclusion, MHY2013 alleviated age-related hepatic lipid accumulation, in part by upregulating ß-oxidation signaling and suppressing inflammation in the liver. Therefore, MHY2013 is a potential pharmaceutical agent for treating age-related hepatic lipid accumulation.

Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver.

Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of Salvia miltiorrhiza. Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARß/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARß/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARß/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-induced increase in the protein levels of a gluconeogenic phosphoenolpyruvate carboxykinase was decreased by MLB. When molecular signaling pathways related to insulin signaling were examined in the liver, MLB supplementation suppressed ER stress- and inflammasome-related signaling molecules induced by aging and obesity. These results suggest that MLB may improve insulin resistance in the liver at least partially by suppressing ER stress and inflammasome formation in aging and obese animal models.

6,6'-Bieckol suppresses inflammatory responses by down-regulating nuclear factor-κB activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells.

OBJECTIVE: Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the pharmaceutical properties of 6,6'-bieckol on the regulation of nuclear factor-κB (NF-κB) activation responsible to the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 using lipopolysaccharide (LPS)-stimulated BV2 and murine primary microglial cells. Meterials and methods: The levels of nitric oxide (NO), prostaglandin E2 (PGE)2, and pro-inflammatory cytokines were measured by Griess assay and enzyme-linked immunosorbent assay. The levels of iNOS, COX-2, mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of NF-κB were determined by immunofluorescence and reporter gene assay, respectively. RESULTS: We found that 6,6'-bieckol decreased the expression of iNOS and COX-2 as well as pro-inflammatory cytokines in LPS-stimulated BV2 and primary microglial cells in a dose-dependent manner. 6,6'-Bieckol inhibited activation of NF-κB by preventing the degradation of inhibitor κB (IκB)-α and led to prevent the nuclear translocation of NF-κB/p65 subunit. Moreover, 6,6'-bieckol inhibited the phosphorylation of Akt, JNK, and p38 MAPK. DISCUSSION AND CONCLUSION: These results indicate that the anti-inflammatory effect of 6,6'-bieckol on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and JNK/p38 MAPK/Akt pathways, supporting biochemical characteristics of the compound for therapeutic agent against neuroinflammatory diseases caused by microglial activation.

(Z)-2-(Benzo[d]thiazol-2-ylamino)-5-(substituted benzylidene)thiazol-4(5H)-one Derivatives as Novel Tyrosinase Inhibitors.

Inhibiting tyrosinase is an important goal to prevent melanin accumulation in skin and thereby to inhibit pigmentation disorders. Therefore, tyrosinase inhibitors are an attractive target in cosmetics and treatments for pigmentation disorders. However, only a few tyrosinase inhibitors are currently available because of their toxic effects to skin or lack of selectivity and stability. Here, we newly synthesized thirteen (Z)-2-(benzo[d]thiazol-2-ylamino)-5-(substituted benzylidene)thiazol-4(5H)-one derivatives and examined their effect on melanogenesis. Of these compounds, MHY2081 had the strongest inhibitory effect on tyrosinase without cytotoxicity in B16F10 melanoma cells. Consistently, melanogenesis was notably decreased by MHY2081 treatment. As an underlying mechanism, docking simulation showed that compared to kojic acid, a well-known competitive tyrosinase inhibitor which forms a hydrogen bond and aromatic interaction with tyrosinase, MHY2081 has stronger affinity with tyrosinase by forming three hydrogen bonds and a hydrophobic interaction with residues of tyrosinase. In parallel with this, Lineweaver-Burk plot analysis showed that MHY2081 is a strong competitive inhibitor of tyrosinase. In conclusion, MHY2081 may be a novel tyrosinase inhibitor for prevention and treatment of pigmentation disorders.

Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice.

AIMS/HYPOTHESIS: Adiponectin is an adipocyte-derived hormone that plays an important role in energy homeostasis. The main objective of this study was to investigate whether or not adiponectin regulates brown adipose tissue (BAT) activation and thermogenesis. METHODS: Core body temperatures (CBTs) of genetic mouse models were monitored at room temperature and during cold exposure. Cultured brown adipocytes and viral vector-mediated gene transduction were used to study the regulatory effects of adiponectin on Ucp1 gene expression and the underlying mechanisms. RESULTS: The CBTs of adiponectin knockout mice (Adipoq(-/-)) were significantly higher than those of wild type (WT) mice both at room temperature and during the cold (4°C) challenge. Conversely, reconstitution of adiponectin in Adipoq(-/-) mice significantly blunted ß adrenergic receptor agonist-induced thermogenesis of interscapular BAT. After 10 days of intermittent cold exposure, Adipoq(-/-) mice exhibited higher UCP1 expression and more brown-like structure in inguinal fat than WT mice. Paradoxically, we found that the anti-thermogenic effect of adiponectin requires neither AdipoR1 nor AdipoR2, two well-known adiponectin receptors. In sharp contrast to the anti-thermogenic effects of adiponectin, AdipoR1 and especially AdipoR2 promote BAT activation. Mechanistically, adiponectin was found to inhibit Ucp1 gene expression by suppressing ß3-adrenergic receptor expression in brown adipocytes. CONCLUSIONS/INTERPRETATION: This study demonstrates that adiponectin suppresses thermogenesis, which is likely to be a mechanism whereby adiponectin reduces energy expenditure.

C/EBPα regulates macrophage activation and systemic metabolism.

Macrophage infiltration plays an important role in obesity-induced insulin resistance. CCAAT enhancer-binding protein-α (C/EBPα) is a transcription factor that is highly expressed in macrophages. To examine the roles of C/EBPα in regulating macrophage functions and energy homeostasis, macrophage-specific C/EBPα knockout (MαKO) mice were created. Chow-fed MαKO mice exhibited higher body fat mass and decreased energy expenditure despite no change in food intake. However, the obese phenotype disappeared after high-fat (HF) diet feeding. Although there was a transient decrease in insulin sensitivity of chow-fed young MαKO mice, systemic insulin sensitivity was protected during HF-feeding due to preserved insulin sensitivity in skeletal muscle. We also found that C/EBPα-deficient macrophages exhibited a blunted response of cytokine-induced expression of M1 and M2 macrophage markers, suggesting that C/EBPα controls both M1 and M2 polarization. Consistent with decreased exercise capacity, mitochondrial respiration rates and signal pathways for fatty acid oxidation were remarkably reduced in the skeletal muscle of chow-fed MαKO mice. Furthermore, expression levels of inflammatory cytokines were reduced in skeletal muscle of HF-fed MαKO mice. Together, these results imply that C/EBPα is required for macrophage activation, which plays an important role in maintaining skeletal muscle energy metabolism.

Adiponectin and energy homeostasis.

White adipose tissue (WAT) is the premier energy depot. Since the discovery of the hormonal properties of adipose-secreted proteins such as leptin and adiponectin, WAT has been classified as an endocrine organ. Although many regulatory effects of the adipocyte-derived hormones on various biological systems have been identified, maintaining systemic energy homeostasis is still the essential function of most adipocyte-derived hormones. Adiponectin is one adipocyte-derived hormone and well known for its effect in improving insulin sensitivity in liver and skeletal muscle. Unlike most other adipocyte-derived hormones, adiponectin gene expression and blood concentration are inversely associated with adiposity. Interestingly, recent studies have demonstrated that, in addition to its insulin sensitizing effects, adiponectin plays an important role in maintaining energy homeostasis. In this review, we summarize the progress of research about 1) the causal relationship of adiposity, energy intake, and adiponectin gene expression; and 2) the regulatory role of adiponectin in systemic energy metabolism.

Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells.

BACKGROUND: Excessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, thus, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Among 5 selected brown algae, we found the highest antioxidant and anti-neuroinflammatory activities from Myagropsis myagroides ethanolic extract (MME) in lipopolysaccharide (LPS)-stimulated BV-2 cells. METHODS: The levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunesorbent assay. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunefluorescence and reporter gene assay, respectively. RESULTS: MME inhibited the expression of iNOS and COX-2 at mRNA and protein levels, resulting in reduction of NO and PGE2 production. As a result, pro-inflammatory cytokines were reduced by MME. MME also inhibited the activation and translocation of NF-κB by preventing inhibitor κB-α (IκB-α) degradation. Moreover, MME inhibited the phosphorylation of extracellular signal regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs). Main anti-inflammatory compound in MME was identified as sargachromenol by NMR spectroscopy. CONCLUSIONS: These results indicate that the anti-inflammatory effect of sargachromenol-rich MME on LPS-stimulated microglia is mainly regulated by the inhibition of IκB-α/NF-κB and ERK/JNK pathways.

Anthocyanins inhibit lipogenesis during adipocyte differentiation of 3T3-L1 preadipocytes.

Anthocyanins have been shown to suppress body weight and fat mass in animal studies. However, the effect of anthocyanins on the process of lipid accumulation during adipocyte differentiation is not fully understood and the lipogenic transcription factors regulated by anthocyanins have not been identified. We investigated the effects of anthocyanins on lipogenesis pathways during adipocyte differentiation in 3T3-L1 cells. Anthocyanins reduced triglyceride (TG) accumulation in a dose-dependent manner during adipocyte differentiation. Accumulation of TG was rapidly reversed by anthocyanin withdrawal. Anthocyanins markedly reduced gene and protein expression levels of lipogenic transcription factors such as liver X receptor α, sterol regulatory element-binding protein-1c, peroxisome proliferators-activated receptor-γ, and CCAAT enhancer-binding protein-α. In addition, the target gene and protein expression of these lipogenic transcription factors such as fatty acid synthase, stearoyl-CoA desaturase-1, and acetyl-CoA carboxylase α were markedly suppressed by anthocyanins. Thus, anthocyanins suppress lipid accumulation in adipocytes due to broad inhibition of the transcription factors regulating lipogenesis. This may partially explain the mechanism by which anthocyanins exert their anti-obesity effect.

LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose Intolerance.

Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

Modulation of macrophage transcript and secretion profiles by Sargassum Serratifolium extract is associated with the suppression of muscle atrophy.

Recent research has emphasized the role of macrophage-secreted factors on skeletal muscle metabolism. We studied Sargassum Serratifolium ethanol extract (ESS) in countering lipopolysaccharide (LPS)-induced changes in the macrophage transcriptome and their impact on skeletal muscle. Macrophage-conditioned medium (MCM) from LPS-treated macrophages (LPS-MCM) and ESS-treated macrophages (ESS-MCM) affected C2C12 myotube cells. LPS-MCM upregulated muscle atrophy genes and reduced glucose uptake, while ESS-MCM reversed these effects. RNA sequencing revealed changes in the immune system and cytokine transport pathways in ESS-treated macrophages. Protein analysis in ESS-MCM showed reduced levels of key muscle atrophy-related proteins, TNF-α, IL-6, IL-1, and GDF-15. These proteins play crucial roles in muscle function. These findings highlight the intricate relationship between the macrophage transcriptome and their secreted factors in either impairing or enhancing skeletal muscle function. ESS treatment has the potential to reduce macrophage-derived cytokines, preserving skeletal muscle function.