Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation.

Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 µM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.

High sucrose intake exacerbates airway inflammation through pathogenic Th2 and Th17 response in ovalbumin (OVA)-induced acute allergic asthma in C57BL/6 mice.

Asthma is an inflammatory disease characterized by chronic inflammation in lung tissues and excessive mucus production. High-fat diets have long been assumed to be a potential risk factor for asthma. However, to date, very few direct evidence indicating the involvement of high sucrose intake (HSI) in asthma progression exists. In this study, we investigate the effect of HSI on ovalbumin (OVA)-sensitized allergic asthma mice. We observed that HSI increased the expression of inflammatory genes (IL-1ß, IL-6, TNF-α) in adipose tissues and led to reactive oxygen species generation in the liver and lung. In addition, HSI accelerated the TLR4/NF-κB signaling pathway leading to MMP9 activation, which promotes the chemokines and TGF-ß secretion in the lungs of OVA-sensitized allergic asthma mice. More importantly, HSI significantly promoted the pathogenic Th2 and Th17 responses. The increase of IL-17A secretion by HSI increased the expression of chemokines (MCP-1, CXCL1, CXCL5, CXCL8). It resulted in eosinophil and mast cell infiltration in the lung and trachea. We also demonstrated that HSI increased mucus hypersecretion, which was validated by increased main mucin protein (MUC5AC) secreted in the lungs. Our findings suggest that HSI exacerbates the development of Th2/Th17-predominant asthma by upregulating the TLR4-mediated NF-κB pathway, leading to excessive MMP9 production.

Immunostimulatory effects of marine algae extracts on in vitro antigen-presenting cell activation and in vivo immune cell recruitment.

Marine algae are photosynthetic eukaryotic organisms that are widely used as sources of food, cosmetics, and drugs. However, their biological and immunological effects on immune cells have not been fully elucidated. To unravel their immunological activity and broaden their application, we generated antigen-presenting cells (APCs), including dendritic cells (DCs) and macrophages, from mouse bone marrow cells and treated them with six different marine algae extracts (MAEs). We evaluated cell viability, activation marker expression, and pro-inflammatory cytokine production by APCs after 2 days of MAE treatment. All six MAEs significantly induced cytokine production of APCs, among which Pyropia yezoensis (PY), Peyssonnelia caulifera (PC), and Meristotheca papulosa (MP) extracts exhibited the strongest effect. Cladophora wrightiana var. minor (CW) extract moderately upregulated cytokine levels but increased the expression of activation markers on DCs. Moreover, PY, PC, MP, Sargassum pectinifera (SP), and Caulerpa okamurae (CO) pre-treated APCs effectively stimulated T-cell proliferation and cytokine production. Furthermore, the mice injected with MAEs exhibited higher cytokine (TNF-α, IL-6, and IL-1ß) production as well as enhanced innate immune cell recruitment capacities (DCs, monocytes, neutrophils, and natural killer cells) in the peritoneal cavity of the mice compared to those of the non-treated mice. Therefore, all MAEs exhibited immunostimulatory potential, with PY, PC, CW, and MP extracts being the most effective in stimulating immune responses and cell activation. To the best of our knowledge, this is the first study to determine the immunomodulatory activities of six MAEs both in vitro and in vivo.

High-Sucrose Diet Accelerates Arthritis Progression in a Collagen-Induced Rheumatoid Arthritis Model.

SCOPE: High dietary sugar and sweeteners are suspected to cause the development of rheumatoid arthritis (RA) symptoms through the induction of proinflammatory cytokine release. However, the mechanisms by which increased dietary sugar affects RA etiology are not yet fully understood. The study uses a mouse model of collagen-induced RA (CIA) to investigate the relationship between excessive sugar consumption and RA risk. METHODS AND RESULTS: RA-associated pathological features are assessed in the nonimmunized (NI) control group, the CIA-positive control group, and the CIA + high-sucrose diet (CIA+HS, 63% calories from sucrose) group. Compared with the CIA group, the CIA+HS group shows a greater increase in paw thickness and clinical scores, as well as, a higher degree of pannus formation and inflammation in the knee, ankle, and sole tissues. Moreover, the infiltration of immune cells is increased in the CIA+HS group. Although the expression of hepatic lipogenic genes, is not altered, that of toll-like receptor (TLR4) and IL-1ß is considerably elevated in the CIA+HS group. CONCLUSIONS: These findings suggest that excessive sucrose consumption causes hepatic fibrosis and inflammation, contributing to the pathophysiology of RA.

Comparative Analysis of Physicochemical Properties and Storability of a New Citrus Variety, Yellowball, and Its Parent.

Although numerous citrus varieties have recently been developed to enhance their quality, information on their quality characteristics is limited. We assessed the quality characteristics of Yellowball, a novel citrus variety, by evaluating its appearance, storability, sensory properties, functionality, and metabolite profiles and then comparing these characteristics with those of its parent varieties, Haruka and Kiyomi. The metabolite profiles between the citrus varieties differed significantly, resulting in distinct physicochemical and functional qualities. The storability of Yellowball was significantly increased compared with that of its parent varieties owing to its strong antifungal activity and unique peel morphology, including the stoma and albedo layers. While we did not investigate the volatile compounds, overall functional activities, and detailed characteristics of each metabolite, our data provide valuable insights into the relationship between citrus metabolites, peel morphology, physicochemical properties, and storability, and demonstrate the potential of Yellowball as a promising variety in the citrus industry.

Excessive sucrose exacerbates high fat diet-induced hepatic inflammation and fibrosis promoting osteoarthritis in mice model.

Osteoarthritis (OA) is marked by chronic low-grade systemic inflammation and cartilage destruction. High fat diet causes obesity and increases the risk of knee OA-development. However, the impact of high dietary sugar intake on OA pathogenesis has not been elucidated yet. Therefore, we investigated the effects of a high-fat and high-sucrose (HF+HS) diet in experimental OA mouse models. Eight-week-old male C57BL/6J mice were fed a standard chow (n=6), high-fat (HF) (n=5), or HF+HS (n=7) diets for 12 weeks; thereafter, the mice underwent surgical destabilization of the medial meniscus (DMM) and received the same experimental diets for an additional 8 weeks. The pathogenesis of knee OA, obesogenic parameters, and inflammation levels in the liver and adipose tissue were investigated. HF+HS diet induced severe cartilage erosion with osteophyte development and subchondral bone plate thickening, indicating that HF+HS diet exacerbated OA. Despite marginal differences in metabolic parameters, hepatic free cholesterol accumulation increased in mice with DMM-induced OA fed on HF+HS diet than in those fed HF diet. Notably, the levels of inflammatory cytokines and fibrosis markers were greater in the livers of mice with DMM-induced OA, fed on HF+HS diet than those in the control group. However, adipose tissue remodeling was not affected by the HF+HS diet. These findings indicate that excess sucrose intake along with a HF diet triggers hepatic inflammation and fibrosis, thereby, contributing to OA pathogenesis.

Attenuation of hepatic fibrosis by p-Coumaric acid via modulation of NLRP3 inflammasome activation in C57BL/6 mice.

A prolonged high-fat and high-sucrose (HFHS) diet induces hepatic inflammation and mediates hepatic stellate cell (HSC) activation, which result in hepatic fibrosis. Aberrant activation of the innate immune system components, such as the NOD-like receptor protein 3 (NLRP3) inflammasome, has been implicated in HSC activation and hepatic fibrosis. We have previously shown that p-coumaric acid (PCA)-enriched peanut sprout extracts exert anti-inflammatory effects. However, it is unknown whether PCA reduces hepatic fibrosis by modulating innate immunity and HSC activation. To test this hypothesis, C57BL/6 male mice were randomly assigned to three groups and fed low-fat (LF) diet (11% calories from fat), high-fat (HF) diet (60% calories from fat, 0.2% cholesterol) with sucrose drink (20% sucrose, HFHS), or HFHS diet with PCA treatment (HFHS+PCA, 50 mg/kg body weight, intraperitoneally) for 13 weeks. The results showed that PCA treatment (1) partly improved systemic insulin sensitivity without altering adiposity, (2) attenuated hepatic signaling pathways associated with NLRP3 inflammasome activation, including toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB), and endoplasmic reticulum/oxidative stress, and (3) reduced circulating interleukin (IL)-1ß levels. More importantly, PCA ameliorated hepatic fibrosis compared to that in the HFHS group, and the anti-fibrogenic effects of PCA were confirmed in vitro in transforming growth factor ß (TGFß) treated-LX-2 HSCs. The role of PCA in decreased NLRP3 activation and caspase-1 cleavage was recapitulated in primary bone marrow‒derived macrophages. These findings indicate that PCA contributes to the prevention of HFHS diet‒mediated liver fibrosis, partly by attenuating the activation of the NLRP3 inflammasome.

Effect of isoflavone supplementation on menopausal symptoms: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVES: Complementary and alternative medicines can be used to alleviate climacteric symptoms that significantly affect the quality of life of postmenopausal women. Isoflavones are the most common plant-based therapies for postmenopausal changes, but the results of previous studies have been controversial. MATERIALS/METHODS: To investigate whether isoflavones would affect menopausal symptoms as well as ovarian hormones, we performed a systematic review and meta-analysis. The PubMed and EMBASE databases were used to perform the systematic search. Included studies were limited to randomized controlled trials (RCTs) assessing the impact of isoflavone supplementation on menopausal symptoms. RESULTS: Eleven studies were included for the final quantitative assessment. Isoflavone intervention was varied between 49.3 and 135 mg of isoflavones per day for 12 wk-2 yrs. The meta-analysis showed that supplementation of isoflavones significantly increased the estradiol levels (standardized mean difference [SMD] = 0.615, P = 0.035) and Kupperman index (SMD = 3.121, P = 0.003) but had no significant effect on hot flashes, follicle-stimulating hormone, and luteinizing hormone. However, both estradiol and the Kupperman index showed significant heterogeneity among studies (I2 = 94.7%, P < 0.001 and I2 = 98.1%, P < 0.001, respectively). CONCLUSIONS: Although the results showed a significant SMD in estradiol and the Kupperman index, the results should be interpreted with caution due to the high heterogeneity. Further validation with a larger RCT will be necessary. Overall, isoflavone supplementation has distinct effects on the climacteric symptoms and hormonal changes in postmenopausal women.

Peanut sprout rich in p-coumaric acid ameliorates obesity and lipopolysaccharide-induced inflammation and the inhibition of browning in adipocytes via mitochondrial activation.

Obesity is accompanied by adipose tissue inflammation that subsequently reduces thermogenic potential in brown and beige (brown-like) adipocytes. We previously reported that peanut sprout (PS) inhibited triglyceride accumulation via fatty acid oxidation in adipocytes. However, it is unknown whether PS reverses diet-induced obesity/inflammation and protects against the inflammation-induced inhibition of browning. To investigate this, C57BL/6 male mice, as an in vivo model, were randomly assigned to three different diets and fed for 8 weeks: (i) low-fat diet (LF, 11% kcal from fat), (ii) high-fat diet (HF, 61% kcal from fat), or (iii) HF diet with PS (4% PS in diet, HF + PS). As an in vitro model, lipopolysaccharides (LPS)-induced macrophages and 3T3-L1 adipocytes in the absence (white adipocytes) or presence of dibutyryl-cAMP (Bt-cAMP, beige adipocytes) were used. The supplementation of PS improved HF-diet-mediated body weight gain, dyslipidemia, and hyperglycemia as compared to the HF group. Although there was a marginal impact on visceral hypertrophy, PS reversed the adipocyte inflammation. In parallel, LPS-mediated induction of inflammation was impeded by PS extract (PSE) in macrophages and adipocytes. PSE also protected against LPS-induced suppression of adipocyte browning in Bt-cAMP-treated adipocytes with mitochondrial activation. The phenolic acid analysis showed that among the constituent of PSE, p-coumaric acid (PCA) was identified as a polyphenol that showed a similar effect to PSE. PCA treatment was also able to maintain a higher temperature than the control group upon cold exposure. Taken together, PCA-enriched PS attenuated HF-diet-induced obesity and protected against LPS-induced inflammation and the inhibition of browning via mitochondrial activation.

RMR-Related MAP2K6 Gene Variation on the Risk of Overweight/Obesity in Children: A 3-Year Panel Study.

From a pilot GWAS, seven MAP2K6 (MEK6) SNPs were significantly associated with resting metabolic rate (RMR) in obese children aged 8-9 years. The aim of this study was to investigate how RMR-linked MEK6 variation affected obesity in Korean children. With the follow-up students (77.9%) in the 3-year panel study, the changes of the variables associated with obesity (such as anthropometrics, blood biochemistry, and dietary intake) were collected. After the MEK6 SNPs were screened by Affymetrix Genome-Wide Human SNP array 6.0, the genotyping of the seven MEK6 SNPs was performed via SNaPshot assay. As the prevalence of obesity (≥85th percentile) increased from 19.4% to 25.5%, the rates of change of the variables RMR, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and dietary intake (energy and carbohydrate intakes) increased. The rate of overweight/obesity was higher in all mutant alleles of the seven MEK6 SNPs than it was in the matched children without mutant alleles. However, over the 3-year study period, RMRs were only significantly increased by the mutants of two single nucleotide polymorphisms (SNPs), rs996229 and rs756942, mainly related to male overweight/obesity as both WC and SBP levels increased. In the mutants of two of the SNPs, the odds ratio of overweight/obesity risk was six times higher in the highest tercile of fat intake and SBP than those of the lowest tercile. For personalized medicine to prevent pediatric obesity, SBP, WC, and dietary fat intake should be observed, particularly if boys have mutants of MEK6 SNPs, rs9916229, or rs756942.

Potential Antidiabetic Effects of Seaweed Extracts by Upregulating Glucose Utilization and Alleviating Inflammation in C2C12 Myotubes.

Seaweed is known to have various health-promoting effects. However, the mechanisms underlying seaweed's antidiabetic effects remain unclear. We investigated the potential antidiabetic effects of seaweed water extracts and further examined their mechanism(s) using C2C12 mouse skeletal muscle cells. Briefly, we screened the physiochemical properties of seven seaweed extracts by comparing the antioxidant and α-glucosidase inhibitory effects. Among them, three seaweed extracts, Undaria pinnatifida sporophyll (UPS), Codium fragile (CF), and Gracilaria verrucosa (GV), were selected for further testing of their possible antidiabetic effects with underlying mechanisms using C2C12 myotubes. Consistent with the superior α-glucosidase inhibition of the three seaweed extracts, the extracts also enhanced glucose utilization in myotubes compared to the control. The upregulated glucose uptake by the seaweed extracts was reversed by an AMP-activated protein kinase (AMPK) inhibitor, compound C, in the UPS- and CF-treated groups. Furthermore, all three seaweed extracts significantly promoted the phosphorylation of AMPK which was completely blocked by pretreating with compound C. In addition, all three extracts reduced lipopolysaccharide-simulated TNF-α production in C2C12 cells. Our results demonstrated that all three seaweed extracts exhibited antidiabetic properties through not only the inhibition of glucose absorption but also the promotion of glucose utilization. Moreover, the regulation of inflammatory cytokine production by the extracts suggested their potential anti-inflammatory property which might play a critical role in protecting insulin sensitivity in a chronic inflammatory state. Taken together, UPS, CF, and GV are a promising source to modulate the glucose absorption and utilization in muscle cells partially via the AMPK pathway.

Ginger (Zingiber officinale) Attenuates Obesity and Adipose Tissue Remodeling in High-Fat Diet-Fed C57BL/6 Mice.

Obesity is characterized by excessive fat accumulation in adipose tissue, which is an active endocrine organ regulating energy metabolism. Ginger (Zingiber officinale) is known to have antioxidant, anti-inflammatory, and antiobesity effects, but the role of ginger in modulating adipocyte metabolism is largely unknown. In this study, we hypothesized that ginger supplementation inhibits high-fat (HF)-diet-mediated obesity. C57BL/6 male mice were randomly assigned to three diets for 7 weeks: low fat (LF, 16% kcal from fat), HF (HF, 60% kcal from fat), or HF with 5% ginger powder in diet (HF + G). The HF diet increased body weight (BW) and BW gain, as well as fasting glucose, total cholesterol, and hepatic lipid levels, compared to the LF diet-fed group. Ginger supplementation significantly improved HF-diet-induced BW gain, hyperglycemia, hypercholesterolemia, and hepatic steatosis without altering food intake. Next, we investigated whether ginger modulates adipocyte remodeling. HF-mediated adipocyte hypertrophy with increased lipogenic levels was significantly improved by ginger supplementation. Furthermore, the HF+G group showed high levels of the fatty-acid oxidation gene, carnitine palmitoyltransferase 1 (CPT1), which was accompanied by a reduction in adipocyte inflammatory gene expression. Taken together, our work demonstrated that ginger supplementation attenuated HF-diet-mediated obesity and adipocyte remodeling in C57BL/6 mice.

Anti-Inflammatory Potential of Cultured Ginseng Roots Extract in Lipopolysaccharide-Stimulated Mouse Macrophages and Adipocytes.

Wild ginseng, Panax ginseng Meyer, is a traditional medicine widely used in Asia. Due to low reward and high costs, wild ginseng is produced by a plant cell culture technique called cultured ginseng roots (GR). The health benefits of wild ginseng have been well studied, but the potential health effects of GR are largely unknown. Thus, we investigated the role of a GR extract (GRE) on inflammatory responses. We firstly investigated the anti-inflammatory potential of GRE in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. GRE (100 µg/mL) dampened pro-inflammatory gene expression, cytokine release, reactive oxygen species (ROS) production, and mitogen-activated protein kinase (MAPK) activation. These anti-inflammatory responses by GRE were confirmed in mouse bone marrow-derived macrophages (BMDMs), which showed that GRE could inhibit inflammation with the induction of antioxidant levels. LPS was recently reported to impair mitochondrial bioenergetics in mouse macrophages. We next measured the mitochondrial oxygen consumption rate (OCR), determining mitochondrial function. LPS treatment downregulated OCR; however, GRE partially restored the LPS-mediated energy homeostasis defects. Furthermore, GRE-pretreated conditioned media (CM) obtained from mouse macrophages decreased CM-mediated adipocyte inflammation. Collectively, these data suggested that GRE attenuated LPS-induced inflammation, and it might be partially involved in the protection from mitochondrial dysfunction in macrophages and adipocytes.

Lipoprotein Lipase Inhibitor, Nordihydroguaiaretic Acid, Aggravates Metabolic Phenotypes and Alters HDL Particle Size in the Western Diet-Fed db/db Mice.

Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoprotein to supply fatty acids, and its deficiency leads to hypertriglyceridemia, thereby inducing metabolic syndrome (MetSyn). Nordihydroguaiaretic acid (NDGA) has been recently reported to inhibit LPL secretion by endoplasmic reticulum (ER)-Golgi redistribution. However, the role of NDGA on dyslipidemia and MetSyn remains unclear. To address this question, leptin receptor knock out (KO)-db/db mice were randomly assigned to three different groups: A normal AIN76-A diet (CON), a Western diet (WD) and a Western diet with 0.1% NDGA and an LPL inhibitor, (WD+NDGA). All mice were fed for 12 weeks. The LPL inhibition by NDGA was confirmed by measuring the systemic LPL mass and adipose LPL gene expression. We investigated whether the LPL inhibition by NDGA alters the metabolic phenotypes. NDGA led to hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. More strikingly, the supplementation of NDGA increased the percentage of high density lipoprotein (HDL)small (HDL3a+3b+3c) and decreased the percentage of HDLlarge (HDL2a+2b) compared to the WD group, which indicates that LPL inhibition modulates HDL subclasses. was NDGA increased adipose inflammation but had no impact on hepatic stress signals. Taken together, these findings demonstrated that LPL inhibition by NDGA aggravates metabolic parameters and alters HDL particle size.

Laminaria japonica Extract Enhances Intestinal Barrier Function by Altering Inflammatory Response and Tight Junction-Related Protein in Lipopolysaccharide-Stimulated Caco-2 Cells.

In the normal physiological state, intestinal epithelial cells act as a defensive frontline of host mucosal immunity to tolerate constant exposure to external stimuli. In this study, we investigated the potential anti-inflammatory and gut permeability protective effects of Laminaria japonica (LJ) water extract (LJE) and three types of fermented Laminaria japonica water extracts (LJE-F1, LJE-F2, and LJE-F3) in lipopolysaccharide (LPS)-stimulated Caco-2, human intestinal epithelial cells. All four extracts significantly decreased the production of nitric oxide and interleukin-6 induced by LPS stimulus. In addition, LJE and the three types of LJE-Fs also inhibited LPS-induced loss of monolayer permeability, as assessed by changes in transepithelial electrical resistance. All four LJ extracts significantly prevented the inhibition of the protein levels of occludin, whereas LJE, LJE-F1, and LJE-F3 significantly attenuated the reduction in phosphorylation of adenosine monophosphate-activated protein kinase compared with the LPS-treated group in Caco-2 cells. In conclusion, LJE and its fermented water extracts appear to have potential gut health-promoting effects by reducing inflammation and partially regulating the tight junction-related proteins in human intestinal epithelial cells. Thus, additional studies are warranted to evaluate Laminaria japonica as a therapeutic agent for inflammatory bowel diseases.

Peanut Sprout Extracts Attenuate Triglyceride Accumulation by Promoting Mitochondrial Fatty Acid Oxidation in Adipocytes.

Peanut sprouts (PS), which are germinated peanut seeds, have recently been reported to have anti-oxidant, anti-inflammatory, and anti-obesity effects. However, the underlying mechanisms by which PS modulates lipid metabolism are largely unknown. To address this question, serial doses of PS extract (PSE) were added to 3T3-L1 cells during adipocyte differentiation. PSE (25 µg/mL) significantly attenuated adipogenesis by inhibiting lipid accumulation in addition to reducing the level of adipogenic protein and gene expression with the activation of AMP-activated protein kinase (AMPK). Other adipocyte cell models such as mouse embryonic fibroblasts C3H10T1/2 and primary adipocytes also confirmed the anti-adipogenic properties of PSE. Next, we investigated whether PSE attenuated lipid accumulation in mature adipocytes. We found that PSE significantly suppressed lipogenic gene expression, while fatty acid (FA) oxidation genes were upregulated. Augmentation of FA oxidation by PSE in mature 3T3-L1 adipocytes was confirmed via a radiolabeled-FA oxidation rate experiment by measuring the conversion of [³H]-oleic acid (OA) to [³H]-H2O. Furthermore, PSE enhanced the mitochondrial oxygen consumption rate (OCR), especially maximal respiration, and beige adipocyte formation in adipocytes. In summary, PSE was effective in reducing lipid accumulation in 3T3-L1 adipocytes through mitochondrial fatty acid oxidation involved in AMPK and mitochondrial activation.

Salt Induces Adipogenesis/Lipogenesis and Inflammatory Adipocytokines Secretion in Adipocytes.

It is well known that high salt intake is associated with cardiovascular diseases including hypertension. However, the research on the mechanism of obesity due to high salt intake is rare. To evaluate the roles of salt on obesity prevalence, the gene expression of adipogenesis/lipogenesis and adipocytokines secretion according to adipocyte dysfunction were investigated in salt-loading adipocytes. High salt dose-dependently increased the expression of adipogenic/lipogenic genes, such as PPAR-γ, C/EBPα, SREBP1c, ACC, FAS, and aP2, but decreased the gene of lipolysis like AMPK, ultimately resulting in fat accumulation. With SIK-2 and Na⁺/K⁺-ATPase activation, salt increased the metabolites involved in the renin-angiotensin-aldosterone system (RAAS) such as ADD1, CYP11ß2, and MCR. Increasing insulin dependent insulin receptor substrate (IRS)-signaling, resulting in the insulin resistance, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Akt-mTOR were activated but AMPK(Thr172) was depressed in salt-loading adipocytes. The expression of pro-inflammatory adipocytokines, TNFα, MCP-1, COX-2, IL-17A, IL-6, leptin, and leptin to adiponectin ratio (LAR) were dose-dependently increased by salt treatment. Using the inhibitors of MAPK/ERK, U0126, we found that the crosstalk among the signaling pathways of MAPK/ERK, Akt-mTOR, and the inflammatory adipogenesis can be the possible mechanism of salt-linked obesity. The possibilities of whether the defense mechanisms against high dose of intracellular salts provoke signaling for adipocytes differentiation or interact with surrounding tissues through other pathways will be explored in future research.

Momordica charantia Ethanol Extract Attenuates H2O2-Induced Cell Death by Its Antioxidant and Anti-Apoptotic Properties in Human Neuroblastoma SK-N-MC Cells.

Oxidative stress, which is induced by reactive oxygen species (ROS), causes cellular damage which contributes to the pathogenesis of neurodegenerative diseases. Momordica charantia (MC), a traditional medicinal plant, is known to have a variety of health benefits, such as antidiabetic, anti-inflammatory, and antioxidant effects. However, it is unknown whether MC has protective effects against oxidative stress-induced neuronal cell death. The aim of this study was to investigate the potential action of MC on oxidative stress induced by H2O2. First, we tested whether the pretreatment of Momordica charantia ethanol extract (MCEE) attenuates H2O2-induced cell death in human neuroblastoma SK-N-MC cells. MCEE pretreatment significantly improved cell viability and apoptosis that deteriorated by H2O2. Further, MCEE ameliorated the imbalance between intracellular ROS production and removal through the enhancement of the intracellular antioxidant system. Intriguingly, the inhibition of apoptosis was followed by the blockage of mitochondria-dependent cell death cascades and suppression of the phosphorylation of the mitogen-activated protein kinase signaling (MAPKs) pathway by MCEE. Taken together, MCEE was shown to be effective in protecting against H2O2-induced cell death through its antioxidant and anti-apoptotic properties.

Anti-Diabetic Effects and Anti-Inflammatory Effects of Laminaria japonica and Hizikia fusiforme in Skeletal Muscle: In Vitro and In Vivo Model.

Laminaria japonica (LJ) and Hizikia fusiforme (HF) are brown seaweeds known to have various health-promoting effects. In this study, we investigated the anti-diabetic effects and possible mechanism(s) of LJ and HF by using both in vitro and in vivo models. C2C12 myotubes, mouse-derived skeletal muscle cells, treated with LF or HF extracts were used for the in vitro model, and muscle tissues from C57BL/6N mice fed a high-fat diet supplemented with 5% LF or HF for 16 weeks were used for the in vivo model. Although both the LF and HF extracts significantly inhibited α-glucosidase activity in a dose-dependent manner, the HF extract had a superior α-glucosidase inhibition than the LF extract. In addition, glucose uptake was significantly increased by LJ- and HF-treated groups when compared to the control group. Phosphorylation of protein kinase B and AMP-activated protein kinase was induced by LJ and HF in both the vivo and in vitro skeletal muscle models. Furthermore, LJ and HF significantly decreased tumor necrosis factor-α whereas both extracts increased interleukin (IL)-6 and IL-10 production in lipopolysaccharide-stimulated C2C12 myotubes. Taken together, these findings imply that the brown seaweeds LJ and HF could be useful therapeutic agents to attenuate muscle insulin resistance due to diet-induced obesity and its associated inflammation.

The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms.

The mitochondrial transcription factor A, or TFAM, is a mitochondrial DNA (mtDNA)-binding protein essential for genome maintenance. TFAM functions in determining the abundance of the mitochondrial genome by regulating packaging, stability, and replication. More recently, TFAM has been shown to play a central role in the mtDNA stress-mediated inflammatory response. Emerging evidence indicates that decreased mtDNA copy number is associated with several aging-related pathologies; however, little is known about the association of TFAM abundance and disease. In this Review, we evaluate the potential associations of altered TFAM levels or mtDNA copy number with neurodegeneration. We also describe potential mechanisms by which mtDNA replication, transcription initiation, and TFAM-mediated endogenous danger signals may impact mitochondrial homeostasis in Alzheimer, Huntington, Parkinson, and other neurodegenerative diseases.