Coenzyme Q0 regulates NFκB/AP-1 activation and enhances Nrf2 stabilization in attenuation of LPS-induced inflammation and redox imbalance: Evidence from in vitro and in vivo studies.

Coenzyme Q (CoQ) analogs with variable number of isoprenoid units have been demonstrated as anti-inflammatory and antioxidant/pro-oxidant molecules. In this study we used CoQ0 (2,3-dimethoxy-5-methyl-1,4-benzoquinone, zero isoprenoid side-chains), a novel quinone derivative, and investigated its molecular actions against LPS-induced inflammation and redox imbalance in murine RAW264.7 macrophages and mice. In LPS-stimulated macrophages, non-cytotoxic concentrations of CoQ0 (2.5-10 µM) inhibited iNOS/COX-2 protein expressions with subsequent reductions of NO, PGE2, TNF-α and IL-1ß secretions. This inhibition was reasoned by suppression of NFκB (p65) activation, and inhibition of AP-1 (c-Jun., c-Fos, ATF2) translocation. Our findings indicated that IKKα-mediated I-κB degradation and MAPK-signaling are involved in regulation of NFκB/AP-1 activation. Furthermore, CoQ0 triggered HO-1 and NQO-1 genes through increased Nrf2 nuclear translocation and Nrf2/ARE-signaling. This phenomenon was confirmed by diminished CoQ0 protective effects in Nrf2 knockdown cells, where LPS-induced NO, PGE2, TNF-α and IL-1ß productions remained high. Molecular evidence revealed that CoQ0 enhanced Nrf2 steady-state level at both transcriptional and translational levels. CoQ0-induced Nrf2 activation appears to be regulated by ROS-JNK-signaling cascades, as evidenced by suppressed Nrf2 activation upon treatment with pharmacological inhibitors of ROS (N-acetylcysteine) and JNK (SP600125). Besides, oral administration of CoQ0 (5 mg/kg) suppressed LPS-induced (1 mg/kg) induction of iNOS/COX-2 and TNF-α/IL-1ß through tight regulation of NFκB/Nrf2 signaling in mice liver and spleen. Our findings conclude that pharmacological actions of CoQ0 are mediated via inhibition of NFκB/AP-1 activation and induction of Nrf2/ARE-signaling. Owing to its potent anti-inflammatory and antioxidant properties, CoQ0 could be a promising candidate to treat inflammatory disorders.

Inhibition of microRNA-328 Increases Ocular Mucin Expression and Conjunctival Goblet Cells.

We previously reported anti-miR-328 therapy for dry eye disease (DED). Since decreased mucin secretion is a risk factor for DED, we aimed to explore whether anti-miR-328 affects mucin expression and goblet cells. MiR-328 was increased in goblet cells when they were under desiccating stress or treated with benzalkonium chloride (BAC), both of which are risk factors for DED. Based on bioinformatics tool results, miR-328 was predicted to directly target the transcription factor CREB1 that has been known to promote the expression of mucin5AC. The inhibitory effect of miR-328 on CREB1 was confirmed by the transfection assay. A miR-328 binding site on the CREB1 gene was confirmed by the luciferase assay. Furthermore, anti-miR-328 increased CREB1 and mucin5AC in cultured goblet cells according to qPCR, Western blot, and IF staining experiments. Anti-miR-328 increased mucin5AC secretion from the cultured goblet cells based on an ELISA assay for the cultured medium. Finally, impression cytology data revealed anti-miR-328 increased conjunctival goblet cells in the DED rabbits induced by BAC. In conclusion, anti-miR-328 increases CREB1 expression leading to an increase in mucin5AC production and secretion. Furthermore, anti-miR-328 also increases conjunctival goblet cells. These results warrant the further development of anti-miR-328 therapy for DED.

Carnosic acid and rosemary extract reversed the lipid accumulation induced by bisphenol A in the 3T3-L1 preadipocytes and C57BL/6J mice via SIRT1/FoxO1 pathway.

Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used to produce polycarbonate plastic. Carnosic acid (CA) is a rosemary diterpene with an anti-obesity effect. In this study, we investigated the anti-adipogenic effect of CA in BPA-treated 3T3-L1 preadipocytes and C57BL/6 J mice. In vitro experiments showed that CA inhibited lipid accumulation by BPA in 3T3-L1 preadipocytes. CA displayed anti-adipogenic effects through the downregulation of differentiation and adipogenesis-related proteins, along with the upregulation of lipolytic protein and SIRT1/FoxO1 pathway. In vivo experiments, mice treated with BPA exhibited an increase in body weight gain and epididymal adipose tissue mass when compared to the control group. CA treatment improved the epididymal adipose tissue mass induced by BPA. CA and rosemary extract (RE) treatment ameliorated dyslipidemia in BPA-treated mice. We further showed that CA and RE exerted anti-adipogenesis effects in liver tissues of BPA-treated mice via increasing SIRT1, FoxO1, and ATGL proteins and decreasing FAS and aP2 proteins. Moreover, SIRT1 inhibitor sirtinol blocked CA to increase SIRT1, FoxO1, FAS, and aP2 proteins, decrease Ac-FoxO1 protein, and reduce lipid accumulation in BPA-treated cells. These findings indicated that CA and RE could reverse BPA-induced lipid accumulation by regulating adipocyte differentiation, adipogenesis, and lipolysis through SIRT1/FoxO1 pathway.

Novel Kefir Exopolysaccharides (KEPS) Mitigate Lipopolysaccharide (LPS)-Induced Systemic Inflammation in Luciferase Transgenic Mice through Inhibition of the NF-κB Pathway.

A novel kefir exopolysaccharides (KEPS) derived from kefir grain fermentation were found to have a small molecular weight (12 kDa) compared to the traditionally high molecular weight (12,000 kDa) of kefiran (KE). KE has been shown to possess antioxidant, blood pressure-lowering, and immune-modulating effects. In this study, we characterized KEPS and KE and evaluated their anti-inflammatory properties in vitro using RAW264.7 macrophages. The main monosaccharide components were identified as glucose (98.1 ± 0.06%) in KEPS and galactose (45.36 ± 0.16%) and glucose (47.13 ± 0.06%) in KE, respectively. Both KEPS and KE significantly reduced IL-6 secretion in lipopolysaccharide (LPS)-stimulated macrophages. We further investigated their effects in LPS-induced systemic injury in male and female NF-κB-luciferase+/+ transgenic mice. Mice received oral KEPS (100 mg/kg) or KE (100 mg/kg) for seven days, followed by LPS or saline injection. KEPS and KE inhibited NF-κB signaling, as indicated by reduced luciferase expression and phosphorylated NF-κB levels. LPS-induced systemic injury increased luciferase signals, especially in the kidney, spleen, pancreas, lung, and gut tissues of female mice compared to male mice. Additionally, it upregulated inflammatory mediators in these organs. However, KEPS and KE effectively suppressed the expression of inflammatory mediators, including p-MAPK and IL-6. These findings demonstrate that KEPS can alleviate LPS-induced systemic damage by inhibiting NF-κB/MAPK signaling, suggesting their potential as a treatment for inflammatory disorders.

MicroRNA Therapy for Dry Eye Disease.

Purpose: We tested the role of microRNA-328 in dry eye disease (DED). Benzalkonium chloride (BAC) has been used to induce DED in animal models. We first demonstrated that both BAC and hyperosmotic stress induced overexpression of miR-328 in corneal cells and then tested whether anti-miR-328 could be a new therapy. Methods: BAC was instilled to both eyes of 41 rabbits and 19 mice from day 0 to 21 to induce DED. Animals of each species were divided to receive topical instillation of saline or anti-miR-328 eye drops between day 8 and 21. The DED signs were assessed by corneal fluorescein staining, histological examination, apoptosis of corneal cells, and inflammatory cytokines in rabbit eyes. For mice, only corneal fluorescein staining was assessed for the therapeutic effects. The corneal fluorescein staining scores ranged from 0 of no staining to 4 of coalescent. Results: For the rabbits, the staining score was significantly reduced (P = 0.038) after the 14-day anti-miR-328 treatment (n = 42 eyes), but the score was not improved by saline treatment (n = 40 eyes). Furthermore, rabbit eyes treated with anti-miR-328 had thicker corneal epithelium (P = 9.4 × 10-5), fewer apoptotic cells in corneal epithelium (P = 0.002), and stroma (P = 0.029) compared with the saline-treated eyes. Anti-miR-328 was more effective than saline to reduce the block of orifices of Meibomian glands, although such an effect was only marginally significant (P = 0.059). Similarly, anti-miR-328 was more effective than saline in reducing corneal staining in mouse eyes (P = 0.005). Conclusion: Overexpression of miR-328 may contribute to DED. Anti-miR-328 protects corneal cells and promotes re-epithelialization for DED treatment.

Conjugated linoleic acid causes a marked increase in liver alpha-tocopherol and liver alpha-tocopherol transfer protein in C57BL/6 J mice.

Conjugated linoleic acid (CLA) is a collective term for the positional and geometric isomers of a conjugated diene of linoleic acid (C18:2, n-6). The aims of the present study were to evaluate whether levels of hepatic alpha-tocopherol, alpha-tocopherol transfer protein (alpha-TTP), and antioxidant enzymes in mice were affected by a CLA-supplemented diet. C57BL/6 J mice were divided into the CLA and control groups, which were fed, respectively, a 5 % fat diet with or without 1 g/100 g of CLA (1:1 mixture of cis-9, trans-11 and trans-10, cis-12) for four weeks. alpha-Tocopherol levels in plasma and liver were significantly higher in the CLA group than in the control group. Liver alpha-TTP levels were also significantly increased in the CLA group, the alpha-TTP/beta-actin ratio being 2.5-fold higher than that in control mice (p<0.01). Thiobarbituric acid-reactive substances were significantly decreased in the CLA group (p<0.01). There were no significant differences between the two groups in levels of three antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). The accumulation of liver alpha-tocopherol seen with the CLA diet can be attributed to the antioxidant potential of CLA and the ability of alpha-TTP induction. The lack of changes in antioxidant enzyme protein levels and the reduced lipid peroxidation in the liver of CLA mice are due to alpha-tocopherol accumulation.

Suppression of LPS-Induced Inflammation by Chalcone Flavokawain A through Activation of Nrf2/ARE-Mediated Antioxidant Genes and Inhibition of ROS/NFκB Signaling Pathways in Primary Splenocytes.

Oxidative stress is an important contributing factor for inflammation. Piper methysticum, also known as Kava-kava, is a shrub whose root extract has been consumed as a drink by the pacific islanders for a long time. Flavokawain A (FKA) is a novel chalcone derived from the kava plant that is known to have medicinal properties. This study was aimed at demonstrating the antioxidant molecular mechanisms mediated by FKA on lipopolysaccharide- (LPS-) induced inflammation in BALB/c mouse-derived primary splenocytes. In vitro data show that the nontoxic concentrations of FKA (2-30 µM) significantly suppressed the proinflammatory cytokine (TNF-α, IL-1ß, and IL-6) release but induced the secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine. It was also shown that FKA pretreatment significantly downregulated the LPS-induced ROS production and blocked the activation of the NFκB (p65) pathway leading to the significant suppression of iNOS, COX-2, TNF-α, and IL-1ß protein expressions. Notably, FKA favored the nuclear translocation of Nrf2 leading to the downstream expression of antioxidant proteins HO-1, NQO-1, and γ-GCLC via the Nrf2/ARE signaling pathway signifying the FKA's potent antioxidant mechanism in these cells. Supporting the in vitro data, the ex vivo data obtained from primary splenocytes derived from the FKA-preadministered BALB/c mice (orally) show that FKA significantly suppressed the proinflammatory cytokine (TNF-α, IL-1ß, and IL-6) secretion in control-, LPS-, or Concanavalin A- (Con A-) stimulated cells. A significant decrease in the ratios of pro- and anti-inflammatory cytokines (IL-6/IL-10; TNF-α/IL-10) showed that FKA possesses strong anti-inflammatory properties. Furthermore, BALB/c mice induced with experimental pancreatitis using cholecystokinin- (CCK-) 8 showed decreased serum lipase levels due to FKA pretreatment. We conclude that with its potent antioxidant and anti-inflammatory properties, chalcone flavokawain A could be a novel therapeutic agent in the treatment of inflammation-associated diseases.

Lactoferrin Protects Hyperoxia-Induced Lung and Kidney Systemic Inflammation in an In Vivo Imaging Model of NF-κB/Luciferase Transgenic Mice.

PURPOSE: High levels of oxygen are usually used in ventilatory support and extracorporeal membrane oxygenation (ECMO) in the intensive care unit of hospitals. Hyperoxia may induce the production of reactive oxygen species (ROS) that can cause lung damage and even systemic injury. In this study, the NF-κB/luciferase transgenic mouse model with non-invasive real-time in vivo imaging was established to test the functions of lactoferrin (LF) in antioxidant and anti-inflammation. PROCEDURES: The NF-κB/luciferase transgenic mice were used to assess the effects of oral administration of LF on attenuation of the systemic inflammatory response and organ damage after 72 h of hyperoxia (FiO2 > 95 %) exposure via monitoring using an in vivo imaging system (IVIS). RESULTS: Using luciferase IVIS imaging, we found that the lungs and kidneys were the most evidently affected organs after hyperoxia treatment. The groups treated with low dose (150 mg/kg) or high dose (300 mg/kg) of LF had lower luciferase expression and less injury, with a dose-dependent effect on the lungs and kidneys. Moreover, ROS, mitogen-activated protein kinases (MAPK), and pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) expression levels were all significantly decreased (P < 0.01), and the protein level of IκB was statistically increased (P < 0.01) after LF treatment. CONCLUSIONS: Our results suggest that hyperoxia can induce systemic inflammation, and the oral administration of LF as a natural antioxidant decreases the production of ROS, attenuates inflammation, and lessens kidney and lung injuries from hyperoxia via the use of live image monitoring of the response in NF-kB/luciferase transgenic mice.

Impairment of glucose metabolism in mice induced by dietary oxidized frying oil is different from that induced by conjugated linoleic acid.

OBJECTIVE: We previously reported that a diet high in oxidized frying oil (OFO) is less adipogenic but induces glucose intolerance in rodents, a situation somewhat is similar to that in conjugated linoleic acid (CLA)-fed mice. The present study compared the lipid and glucose metabolism effects of dietary OFO and CLA to clarify how the OFO diet compromises glucose tolerance. METHODS: C57BL/6J mice were divided into four groups in which the CLA and CLA control (CC) groups received a low-fat diet supplemented with or without 1 g/100 g of CLA (1:1 mixture of cis-9, trans-11 and trans-10, cis-12), and the OFO and OFO control (CO) groups received a high-fat diet containing 20 g/100 g of OFO or fresh soybean oil, respectively. RESULTS: When compared with their respective controls (CLA versus CC and OFO versus CO), the OFO and CLA diets resulted in deprivation of adipose and downregulation of adipocyte marker genes, but a totally different response of lipid metabolism in the liver was observed, i.e., anabolism was enhanced by the CLA diet but catabolism was enhanced by the OFO diet. In contrast to the insulin resistance that occurred in CLA-fed mice, the glucose intolerance induced by the OFO diet was accompanied by decreases in insulin and C-peptide levels during an oral glucose tolerance test. Analysis of vitamin E and thiobarbituric acid-reactive substances in the liver showed the OFO diet, but not the CLA diet, compromised vitamin E status. CONCLUSION: The impaired glucose metabolism resulting from OFO feeding is not related to CLA. In contrast to the hyperinsulinemia and insulin resistance induced by the CLA diet, the OFO diet-induced glucose intolerance is mediated by impairment of insulin secretion.

Induction of Nrf2-mediated genes by Antrodia salmonea inhibits ROS generation and inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.

Antrodia salmonea (AS), a well-known medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, anti-atherogenic, and anti-inflammatory effects. In the present study, we investigated the activation of Nrf2-mediated antioxidant genes in RAW264.7 macrophages by the fermented culture broth of AS, studied the resulting protection against lipopolysaccharide (LPS)-stimulated inflammation, and revealed the molecular mechanisms underlying these protective effects. We found that non-cytotoxic concentrations of AS (25-100 µg mL⁻¹) protected macrophages from LPS-induced cell death and ROS generation in a dose-dependent manner. The antioxidant potential of AS was directly correlated with the increased expression of the antioxidant genes HO-1, NQO-1, and γ-GCLC, as well as the level of intracellular GSH followed by an increase in the nuclear translocation and transcriptional activation of the Nrf2-ARE pathway. Furthermore, Nrf2 knockdown diminished the protective effects of AS, as evidenced by the increased production of pro-inflammatory cytokines and chemokines, including PGE2, NO, TNF-α, and IL-1ß, in LPS-stimulated macrophages. Notably, AS treatment significantly inhibited LPS-induced ICAM-1 expression in macrophages. Our data suggest that the anti-inflammatory potential of Antrodia salmonea is mediated by the activation of Nrf2-dependent antioxidant defense mechanisms. Results support the traditional usage of this beneficial mushroom for the treatment of free radical-related diseases and inflammation.

Antrodia salmonea inhibits TNF-α-induced angiogenesis and atherogenesis in human endothelial cells through the down-regulation of NF-κB and up-regulation of Nrf2 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Antrodia salmonea (AS) is known as a traditional Chinese medicine, but very few biological activities have been reported. MATERIALS AND METHODS: The present study was aimed to investigate the anti-angiogenic and anti-atherosclerotic potential of the fermented culture broth of AS against tumor necrosis factor-α (TNF-α)-stimulated human endothelial (EA.hy 926) cells. RESULTS: The non-cytotoxic concentrations of AS significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation in EA.hy 926 cells. Furthermore, AS suppressed TNF-α-induced activity and expression of matrix metalloproteinase-9 (MMP-9), and cell-surface expression of intercellular adhesion molecule-1 (ICAM-1), which was associated with abridged adhesion of U937 leukocytes to endothelial cells. Moreover, AS significantly down-regulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor κB (NF-κB) followed by suppression of I-κB degradation and phosphorylation of I-κB kinase-α (IKKα). Notably, the protective effect of AS was directly correlated with the increased expression of hemeoxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCLC), which was reasoned by nuclear translocation and transactivation of NF-E2 related factor-2 (Nrf2)/antioxidant response element (ARE). Furthermore, HO-1 knockdown by HO-1-specific shRNA diminished the protective effects of AS on TNF-α-stimulated invasion, tube formation, and U937 adhesion in EA.hy 926 cells. CONCLUSIONS: Taken together, these results suggest that Antrodia salmonea may be useful for the prevention of angiogenesis and atherosclerosis.

Purified active lotus plumule (Nelumbo nucifera Gaertn) polysaccharides exert anti-inflammatory activity through decreasing toll-like receptor-2 and -4 expressions using mouse primary splenocytes.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Lotus plumule is widely used as traditional Chinese medicine. Among the active components in lotus plumule, polysaccharides exhibit promising potential for its potent anti-inflammatory effects. However, the anti-inflammatory mechanism of purified polysaccharides from lotus plumule remains unknown. To evaluate their anti-inflammatory potential and possible mechanisms of purified polysaccharides in lotus plumule, two active lotus plumule polysaccharides, fractions F1 and F2, were subjected to assay their anti-inflammatory potential and possible mechanisms using murine primary splenocytes in the absence or presence of lipopolysaccharide (LPS). MATERIALS AND METHODS: Two purified active lotus plumule polysaccharides, F1 and F2, were cultured independently with murine primary splenocytes in the absence or presence of LPS under four different experiment models in vitro. Changes in pro-inflammatory IL-1ß, IL-6 and TNF-α, as well as anti-inflammatory IL-10 cytokines secreted by the treated splenocytes were determined using an enzyme-linked immunosorbent assay (ELISA). The amount of toll-like receptor (TLR)-2 and TLR-4 mRNA expression levels in the cells were quantitated using a two-step real-time polymerase chain reaction (PCR) assay. RESULTS: The results showed that F1 and F2 treatments alone, particularly F2, significantly (P<0.05) decreased pro-/anti-inflammatory (IL-1ß/IL-10 and TNF-α/IL-10) cytokine secretion ratios dose-dependently. F1 and F2 treatments in the presence of LPS significantly decreased TLR-2 and/or TLR-4 mRNA expression levels in the splenocytes under inflammatory and repair experiment models. CONCLUSIONS: The present study proved that F1 and F2 had strong anti-inflammatory effects through inhibiting TLR-2 and/or TLR-4 expressions in the splenocytes in normal, inflammatory and repair situations. Our results further suggest that F2, which is a glycoprotein with low molecular weight of 25.7 kDa, may serve as a promising lead for the development of selective TLR antagonistic agents for inflammatory diseases.

Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide ameliorates pancreatic islets loss and serum lipid profiles in non-obese diabetic mice.

To unravel possible protective effects of a newly isolated lotus plumule polysaccharide (LPPS) on type 1 diabetes (T1D), this study isolated LPPS and administered it to non-obese diabetic (NOD) female mice for 15 weeks. Oral glucose tolerance, serum ketone body, glucose, insulin, and lipid levels, as well as pancreatic islet cell numbers and the insulin secretion ability of the experimental mice were determined. The results showed that LPPS administration in vivo significantly (P<0.05) increased pancreatic islet cell numbers and slightly enhanced the basal insulin secretion ability compared to the control group. LPPS administration improved serum lipid profiles in the diabetic mice via relatively increasing serum high density lipoprotein-cholesterol, but decreasing low density lipoprotein-cholesterol and total cholesterol levels. The present study suggests that LPPS supplementation may ameliorate T1D progress and its complications through protecting pancreatic islets and modulating serum lipid profiles.

Purification, partial characterization and anti-inflammatory characteristics of lotus (Nelumbo nucifera Gaertn) plumule polysaccharides.

A novel lotus plumule polysaccharide (LPPS) was purified, characterised and cultured with RAW264.7 macrophages to evaluate its anti-inflammatory characteristics. LPPS was purified using Sepharose 6B gel filtration and dissolved into two major components, fraction-1 (F1) and fraction-2 (F2). The molecular weights of native F1 and F2 were approximately distributed at >2,000 and 25.7kDa, respectively. The total protein and carbohydrate constituent ratios in LPPS, F1, and F2 were 30.0±0.9% vs. 70.0±0.9%, 30.1±2.6% vs. 69.9±2.6%, and 96.5±6.1% vs. 3.5±6.1% (w/w), respectively, suggesting that F1 may be a major proteo-polysaccharide component and F2 a glycoprotein constituent in LPPS. Pro-/anti-inflammatory (IL-6/IL-10) cytokine secretion ratios by lipopolysaccharide-stimulated RAW264.7 macrophages were significantly decreased by F1 and F2 treatments, particularly by F2, in a dose-dependent manner under a preventive experimental model. This study suggests that purified components, F1 and F2 from LPPS, have strong anti-inflammatory effects on LPS-induced inflamed macrophages in a preventive manner.

Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide protects the spleen and liver from spontaneous inflammation in non-obese diabetic mice by modulating pro-/anti-inflammatory cytokine gene expression.

A novel lotus plumule polysaccharide (LPPS) was administered to non-obese diabetic (NOD) mice for 15weeks to evaluate the protective effects of LPPS on type 1 diabetes. After the 15-week feeding experiment, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 expressions in the spleen, liver and kidney of the experimental mice were measured using enzyme-linked immunosorbent assay or real-time quantitative polymerase chain reaction assay. The results showed that LPPS significantly (p<0.05) decreased the absolute weights of the enlarged spleens in the NOD mice in a dose-dependent manner, inhibited pro-inflammatory TNF-α and IL-6 cytokine production and decreased the secretion ratio of IL-6/IL-10 in splenocyte cultures. LPPS markedly decreased the relative expression of pro-/anti-inflammatory cytokine genes (TNF-α/IL-10 and IL-6/IL-10) in the livers of NOD mice. Our results suggest that LPPS protected the spleen and liver from spontaneous inflammation in NOD mice by modulating pro-/anti-inflammatory cytokine gene expression.

A high oxidised frying oil content diet is less adipogenic, but induces glucose intolerance in rodents.

Oxidised frying oil (OFO) and fish oil have been shown to be peroxisome proliferator-activated receptor (PPAR)alpha activators and their ingestion results in pleotropic peroxisome proliferator responses in rats. To examine the effect of dietary OFO on adiposity, four groups of weanling Sprague-Dawley rats were fed isoenergetically with, respectively, a low fat basal diet containing 5 g/100 g of fresh soybean oil (LSB) or a high fat diet containing 20 g/100 g of fresh soybean oil (HSB), OFO (HO) or fish oil (HF). The tissue mass, cell size and lipid/DNA ratio in the retroperitoneal fat pad and serum leptin levels were lowest in the HO group (P < 0.05), indicating that dietary OFO has a greater anti-adipogenic action than dietary fish oil. However, a tendency to hyperglycaemia was observed in the HO group (P = 0.0528). To examine the effect of dietary OFO on glucose tolerance, three groups of rats and three groups of mice were fed, respectively, the LSB, HSB or HO diet, and an oral glucose tolerance test was performed. After oral glucose load, the area under the curve for blood glucose (AUCglu) over 2 h was significantly higher, and that for serum insulin (AUCins) over 90 min was significantly lower, in the HO group than in the other two groups (P < 0.05). These results demonstrate that, in rats and mice, a high OFO diet is less adipogenic, but induces glucose intolerance.