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Pharmaceuticals (Basel, Switzerland) May 2024Pearl oysters have been extensively utilized in pearl production; however, most pearl oyster shells are discarded as industrial waste. In a previous study, we...
Pearl oysters have been extensively utilized in pearl production; however, most pearl oyster shells are discarded as industrial waste. In a previous study, we demonstrated that the intraperitoneal administration of pearl oyster shell-derived nacre extract (NE) prevented d-galactose-induced brain and skin aging. In this study, we examined the anti-aging effects of orally administered NE in senescence-accelerated mice (SAMP8). Feeding SAMP8 mice NE prevented the development of aging-related characteristics, such as coarse and dull hair, which are commonly observed in aged mice. Additionally, the NE mitigated muscle aging in SAMP8 mice, such as a decline in grip strength. Histological analysis of skeletal muscle revealed that the NE suppressed the expression of aging markers, cyclin-dependent kinase inhibitor 2A (p16) and cyclin-dependent kinase inhibitor 1 (p21), and increased the expression of sirtuin1 and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1)- α, which are involved in muscle synthesis. These findings suggest that the oral administration of NE suppresses skeletal muscle aging. Moreover, NE administration suppressed skin aging, including a decline in water content. Interestingly, oral administration of NE significantly extended the lifespan of SAMP8 mice, suggesting that its effectiveness as an anti-aging agent of various tissues including skeletal muscle, skin, and adipose tissue.
PubMed: 38931380
DOI: 10.3390/ph17060713 -
Nutrients Jun 2024High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and...
BACKGROUND
High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD).
RESULTS
C57BL/6 mice (5-6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. , and were highly abundant in C-HFD group, while the , (TM7), , and were more abundant in F-HFD group. Other taxa in C-HFD group included the (AF12), and An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (), Fatty acid synthase (), Stearoyl-CoA desaturase-1 (), Elongation of long-chain fatty acids family member 6 (), Peroxisome proliferator-activated receptor-gamma () and cholesterol synthesis (β-(hydroxy β-methylglutaryl-CoA reductase (). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (), Fatty acid binding protein-1 () and efflux (ATP-binding cassette G1 (), Microsomal TG transfer protein () in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (), C-C motif chemokine ligand 2 (), and Interleukin-12 (), as well as a tendency for liver fibrosis.
CONCLUSION
These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance.
Topics: Animals; Dysbiosis; Gastrointestinal Microbiome; Insulin Resistance; Diet, High-Fat; Mice, Inbred C57BL; Male; Mice; Fatty Liver; Liver; Dietary Fats; Sucrose
PubMed: 38931284
DOI: 10.3390/nu16121929 -
Animals : An Open Access Journal From... Jun 2024The present study aimed to investigate the impacts of dietary standardized ileal digestible lysine to net energy (SID Lys:NE) ratio on lipid metabolism in pigs fed...
The present study aimed to investigate the impacts of dietary standardized ileal digestible lysine to net energy (SID Lys:NE) ratio on lipid metabolism in pigs fed high-wheat diets. Thirty-six crossbred growing barrows (65.20 ± 0.38 kg) were blocked into two treatment groups, fed high-wheat diets with either a high SID Lys:NE ratio (HR) or a low SID Lys:NE ratio (LR). Each treatment group consisted of three replicates, with six pigs per pen in each replicate. The diminishing dietary SID Lys:NE ratio exhibited no adverse impacts on the carcass trait ( > 0.05) but increased the marbling score of the longissimus dorsi muscle ( < 0.05). Meanwhile, LR diets tended to increase the serum triglyceride concentration ( < 0.1). LR diets upregulated fatty acid transport protein 4 and acetyl-coA carboxylase α expression levels and downregulated the expression level of adipose triglyceride lipase ( < 0.05). LR diets improved energy metabolism via decreasing the expression levels of AMP-activated protein kinase (AMPK) α1, sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) ( < 0.05). Additionally, LR diets stimulated hepatic bile acid synthesis via upregulating the expression levels of cytochrome P450 family 7 subfamily A member 1 and cytochrome P450 family 27 subfamily A member 1, and downregulating farnesol X receptor (FXR) and small heterodimer partner (SHP) expression levels ( < 0.05). A lowered SID Lys:NE ratio affected the colonic microbial composition, characterized by increased relative abundances of , , , and , alongside a decreased in the proportion of , , , , , , , , and ( < 0.05). The alterations in microbial composition were accompanied by a decrease in colonic butyrate concentration ( < 0.1). The metabolomic analysis revealed that LR diets affected primary bile acid synthesis and AMPK signaling pathway ( < 0.05). And the mantel analysis indicated that , , , , and contributed to the alterations in body metabolism. A reduced dietary SID Lys:NE ratio improves energy metabolism, stimulates lipogenesis, and inhibits lipolysis in finishing pigs by regulating the AMPKα/SIRT1/PGC-1α pathway and the FXR/SHP pathway. and benefited bile acids synthesis, whereas , , and may contribute to the activation of the AMPK signaling pathway. Overall, body metabolism and colonic microbiota collectively controlled the lipid metabolism in finishing pigs.
PubMed: 38929443
DOI: 10.3390/ani14121824 -
Foods (Basel, Switzerland) Jun 2024A whole-grain highland barley (WHB) diet has been recognized to exhibit the potential for alleviating hyperlipidemia, which is mainly characterized by lipids...
Procyanidin B1 and Coumaric Acid from Highland Barley Alleviated High-Fat-Diet-Induced Hyperlipidemia by Regulating PPARα-Mediated Hepatic Lipid Metabolism and Gut Microbiota in Diabetic C57BL/6J Mice.
A whole-grain highland barley (WHB) diet has been recognized to exhibit the potential for alleviating hyperlipidemia, which is mainly characterized by lipids accumulation in the serum and liver. Previously, procyanidin B1 (PB) and coumaric acid (CA) from WHB were found to alleviate serum lipid accumulation in impaired glucose tolerance mice, while the effect on modulating the hepatic lipid metabolism remains unknown. In this study, the results showed the supplementation of PB and CA activated the expression of peroxisome proliferator-activated receptor α (PPARα) and the target genes of cholesterol 7-α hydroxylase () and carnitine palmitoyl transferase I () in the liver cells of high-fat-diet (HFD)-induced diabetic C57BL/6J mice, resulting in decreases in the serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL-C) contents, and an increase in the high-density lipoprotein (HDL-C) content. High-throughput sequencing of 16S rRNA indicated that supplementation with PB and CA ameliorated the gut microbiota dysbiosis, which was associated with a reduction in the relative abundance of and an increase in the relative abundance of , and . Spearman's correlation analysis revealed that these genera were closely related to obesity-related indices. In summary, the activation of PPARα expression by PB and CA from WHB was important for the alleviation of hyperlipidemia and the structural adjustment of the gut microbiota.
PubMed: 38928784
DOI: 10.3390/foods13121843 -
International Journal of Molecular... Jun 2024Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins...
Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells ( < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased ( < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.
Topics: Humans; Foam Cells; Cholesterol; Liver X Receptors; Toll-Like Receptors; ATP Binding Cassette Transporter 1; Lipoproteins, LDL; PPAR gamma; THP-1 Cells; Macrophages; ATP Binding Cassette Transporter, Subfamily G, Member 1; Lipopolysaccharides; Scavenger Receptors, Class B
PubMed: 38928513
DOI: 10.3390/ijms25126808 -
International Journal of Molecular... Jun 2024The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases,...
The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases, ultimately contributing to a decreased lifespan and quality of life. Much effort has been made to surmise the molecular mechanisms underlying muscle atrophy and develop tools for improving muscle function. Enhancing mitochondrial function is considered critical for increasing muscle function and health. This study is aimed at evaluating the effect of an aqueous extract of (GTAE) on myogenesis and muscle atrophy caused by dexamethasone (DEX). The GTAE promoted myogenic differentiation, accompanied by an increase in peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) expression and mitochondrial content in myoblast cell culture. In addition, the GTAE alleviated the DEX-mediated myotube atrophy that is attributable to the Akt-mediated inhibition of the Atrogin/MuRF1 pathway. Furthermore, an in vivo study using a DEX-induced muscle atrophy mouse model demonstrated the efficacy of GTAE in protecting muscles from atrophy and enhancing mitochondrial biogenesis and function, even under conditions of atrophy. Taken together, this study suggests that the GTAE shows propitious potential as a nutraceutical for enhancing muscle function and preventing muscle wasting.
Topics: Animals; Muscular Atrophy; Dexamethasone; Muscle Development; Mice; Plant Extracts; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Cell Differentiation; Myoblasts; Cell Line; Muscle Proteins; Male; Muscle, Skeletal; Muscle Fibers, Skeletal; Mice, Inbred C57BL; Tripartite Motif Proteins; Rhodophyta
PubMed: 38928510
DOI: 10.3390/ijms25126806 -
International Journal of Molecular... Jun 2024Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced...
Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase-γ (PI3K-γ) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K-γ remain unclear. We hypothesized that MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K-γ pathway. Five days after receiving a single bolus of 0.075 units of bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg of MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-β1, oxidative loads, Masson's trichrome staining, extracellular collagen levels, positive staining of α-smooth muscle actin, PI3K-γ expression, and myonuclear apoptosis ( < 0.05). Decreased diaphragm contractility and peroxisome proliferator-activated receptor-γ coactivator-1α levels were also observed ( < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K-γ activity ( < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated by PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.
Topics: Animals; Bleomycin; Diaphragm; Mice; Fibrosis; Disease Models, Animal; Mice, Inbred C57BL; Acute Lung Injury; Male; Respiration, Artificial; Class Ib Phosphatidylinositol 3-Kinase; Transforming Growth Factor beta1; Apoptosis; Quinoxalines; Thiazolidinediones
PubMed: 38928077
DOI: 10.3390/ijms25126370 -
Bioengineering (Basel, Switzerland) Jun 2024To characterize transforming growth factor-β (TGF-β) isoform (TGF-β1~3)-b's biological effects on the human retinal pigment epithelium (RPE) under normoxia and...
To characterize transforming growth factor-β (TGF-β) isoform (TGF-β1~3)-b's biological effects on the human retinal pigment epithelium (RPE) under normoxia and hypoxia conditions, ARPE19 cells cultured by 2D (two-dimensional) and 3D (three-dimensional) conditions were subjected to various analyses, including (1) an analysis of barrier function by trans-epithelial electrical resistance (TEER) measurements; (2) qPCR analysis of major ECM molecules including , , and ; ; ; and , a master regulator for mitochondrial respiration;, tight junction-related molecules, and ; and ; (3) physical property measurements of 3D spheroids; and (4) cellular metabolic analysis. Diverse effects among TGF-β isoforms were observed, and those effects were also different between normoxia and hypoxia conditions: (1) TGF-β1 and TGF-β3 caused a marked increase in TEER values, and TGF-β2 caused a substantial increase in TEER values under normoxia conditions and hypoxia conditions, respectively; (2) the results of qPCR analysis supported data obtained by TEER; (3) 3D spheroid sizes were decreased by TGF-β isoforms, among which TGF-β1 had the most potent effect under both oxygen conditions; (4) 3D spheroid stiffness was increased by TGF-β2 and TGF-β3 or by TGF-β1 and TGF-β3 under normoxia conditions and hypoxia conditions, respectively; and (5) the TGF-β isoform altered mitochondrial and glycolytic functions differently under oxygen conditions and/or culture conditions. These collective findings indicate that the TGF-β-induced biological effects of 2D and 3D cultures of ARPE19 cells were substantially diverse depending on the three TGF-β isoforms and oxygen levels, suggesting that pathological conditions including epithelial-mesenchymal transition (EMT) of the RPE may be exclusively modulated by both factors.
PubMed: 38927817
DOI: 10.3390/bioengineering11060581 -
Genes Jun 2024Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and...
Peroxisome proliferator-activated receptor γ (PPARG) has various splicing variants and plays essential roles in the regulation of adipocyte differentiation and lipogenesis. However, little is known about the expression pattern and effect of the PPARG on milk fat synthesis in the buffalo mammary gland. In this study, we found that only and of the splicing variant were expressed in the buffalo mammary gland. Amino acid sequence characterization showed that the proteins encoded by and are endonuclear non-secreted hydrophilic proteins. Protein domain prediction found that only the -encoded protein had PPAR ligand-binding domains (NR_LBD_PPAR), which may lead to functional differences between the two splices. RNA interference (RNAi) and the overexpression of and in buffalo mammary epithelial cells (BMECs) were performed. Results showed that the expression of fatty acid synthesis-related genes (, , , , , ) was significantly modified ( < 0.05) by the RNAi and overexpression of and . All kinds of FAs detected in this study were significantly decreased ( < 0.05) after RNAi of or . Overexpression of or significantly decreased ( < 0.05) the SFA content, while significantly increased ( < 0.05) the UFA, especially the MUFA in the BMECs. In conclusion, there are two splicing variants expressed in the BMECs that can regulate FA synthesis by altering the expression of diverse fatty acid synthesis-related genes. This study revealed the expression characteristics and functions of the gene in buffalo mammary glands and provided a reference for further understanding of fat synthesis in buffalo milk.
Topics: Animals; Buffaloes; PPAR gamma; Mammary Glands, Animal; Female; Epithelial Cells; Alternative Splicing; Fatty Acids; Protein Isoforms; Milk
PubMed: 38927715
DOI: 10.3390/genes15060779 -
Biomolecules Jun 2024Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin... (Review)
Review
Peroxisome proliferator-activated receptor gamma (PPARγ) is a transcription factor expressed in many tissues, including skin, where it is essential for maintaining skin barrier permeability, regulating cell proliferation/differentiation, and modulating antioxidant and inflammatory responses upon ligand binding. Therefore, PPARγ activation has important implications for skin homeostasis. Over the past 20 years, with increasing interest in the role of PPARs in skin physiopathology, considerable effort has been devoted to the development of PPARγ ligands as a therapeutic option for skin inflammatory disorders. In addition, PPARγ also regulates sebocyte differentiation and lipid production, making it a potential target for inflammatory sebaceous disorders such as acne. A large number of studies suggest that PPARγ also acts as a skin tumor suppressor in both melanoma and non-melanoma skin cancers, but its role in tumorigenesis remains controversial. In this review, we have summarized the current state of research into the role of PPARγ in skin health and disease and how this may provide a starting point for the development of more potent and selective PPARγ ligands with a low toxicity profile, thereby reducing unwanted side effects.
Topics: PPAR gamma; Humans; Animals; Skin; Skin Neoplasms; Skin Diseases; Ligands; Cell Differentiation
PubMed: 38927131
DOI: 10.3390/biom14060728