Effects of Caprylic Acid and Eicosapentaenoic Acid on Lipids, Inflammatory Levels, and the JAK2/STAT3 Pathway in ABCA1-Deficient Mice and ABCA1 Knock-Down RAW264.7 Cells.

Our previous studies have found that caprylic acid (C8:0) can improve blood lipids and reduce inflammation levels and may be related to the upregulation of the p-JAK2/p-STAT3 pathway by ABCA1. This study aims to investigate the effects of C8:0 and eicosapentaenoic acid (EPA) on lipids, inflammatory levels, and the JAK2/STAT3 pathway in ABCA1-deficient mice (ABCA1-/-) and ABCA1 knock-down (ABCA1-KD) RAW 264.7 cells. Twenty 6-week ABCA1-/- mice were randomly divided into four groups and fed a high-fat diet, or a diet of 2% C8:0, 2% palmitic acid (C16:0) or 2% EPA for 8 weeks, respectively. The RAW 264.7 cells were divided into the control or control + LPS group, and the ABCA1-KD RAW 264.7 cells were divided into ABCA1-KD with LPS (LPS group), ABCA1-KD with LPS + C8:0 (C8:0 group), and ABCA1-KD with LPS + EPA (EPA group). Serum lipid profiles and inflammatory levels were measured, and ABCA1 and JAK2/STAT3 mRNA and protein expressions were determined by RT-PCR and Western blot analyses, respectively. Our results showed that serum lipid and inflammatory levels increased in ABCA1-/- mice (p < 0.05). After the intervention of different fatty acids in ABCA1-/- mice, TG and TNF-α were significantly lower, while MCP-1 increased significantly in the C8:0 group (p < 0.05); however, LDL-C, TC, TNF-α, IL-6, and MCP-1 levels decreased significantly and IL-10 increased significantly in the EPA group (p < 0.05). In the aorta of ABCA1-/- mice, C8:0 significantly decreased p-STAT3 and p-JAK2 mRNA, while EPA significantly reduced TLR4 and NF-κBp65 mRNA. In the ABCA1-KD RAW 264.7 cells, TNF-α and MCP-1 were increased significantly and IL-10 and IL-1ß were significantly decreased in the C8:0 group (p < 0.05). The protein expressions of ABCA1 and p-JAK2 were significantly higher, and the NF-κBp65 was significantly lower in the C8:0 and EPA groups (p < 0.05). Meanwhile, compared to the C8:0 group, the NF-κBp65 protein expression was significantly lower in the EPA group (p < 0.05). Our study showed that EPA had better effects than C8:0 on inhibiting inflammation and improving blood lipids in the absence of ABCA1. C8:0 may be involved mainly in inhibiting inflammation through upregulation of the ABCA1 and p-JAK2/p-STAT3 pathways, while EPA may be involved mainly in inhibiting inflammation through the TLR4/NF-κBp65 signaling pathway. The upregulation of the ABCA1 expression pathway by functional nutrients may provide research targets for the prevention and treatment of atherosclerosis.

Dietary fiber intake, dietary glycemic load, and the risk of gestational diabetes mellitus during the second trimester: A nested case-control study.

BACKGROUND AND OBJECTIVES: The effect of fiber, especially the effect of specific fiber in different food groups, on gestational diabetes mellitus (GDM) has seldomly been investigated. This study aimed to examine the association between GDM risk and consumption of total fiber, fiber in specific food groups, and glycemic load (GL) in the second trimester in Chinese women. METHODS AND STUDY DESIGN: A total 162 GDM cases were matched to 324 controls on women's age and pre-pregnancy BMI. Dietary survey was conducted twice to evaluate dietary factors between 13-16 gestational weeks (GW) and 21-24 GW respectively. Multivariable logistic regression analysis was used to compute the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Intake of total fiber and fruit fiber in both 13-16 GW and in 21-24 GW were significantly correlated with decreased risk of GDM, with adjusted ORs (95% CIs): 0.06 (0.03-0.13) and 0.03 (0.01-0.08) for total fiber in the highest quartile, 0.003 (0.0002-0.02) and 0.01 (0.001-0.02) for fruit fiber in the highest quartile, respectively. In contrast, consumption of cereal fiber in 21-24 GW and daily average GL in 13-16 GW were positively associated with GDM risk, with adjusted ORs (95% CIs) of the highest quartile: 3.34 (1.45-7.92) and 3.88 (1.43-10.89) respectively. CONCLUSIONS: Our findings suggested consumption of dietary fiber in various food groups in the second trimester might be associated with GDM risk. Particularly, diet rich in total fiber and fruit fiber may play a protective role.

Medium-chain triglycerides improved cognition and lipid metabolomics in mild to moderate Alzheimer's disease patients with APOE4-/-: A double-blind, randomized, placebo-controlled crossover trial.

BACKGROUND: Previous clinical and animal studies suggested that medium-chain triglycerides (MCT) might be an alternative energy substrate for the brain and might benefit patients with Alzheimer's disease (AD), but the clinical evidence is not substantial or totally convincing. OBJECTIVE: To investigate the effects of MCT on cognitive ability in patients with mild to moderate AD and explore the changes in peripheral blood metabolomics. METHODS: A double-blind, randomized, placebo-controlled crossover study was undertaken in 53 mild to moderate AD patients. Participants were randomized between two sequences (placebo followed by MCT or MCT followed by placebo) and took MCT jelly or placebo jelly (canola oil) by mouth three times daily (total daily fat dose: 17.3 g MCT, or 19.7 g canola oil) for 30 days per phase. The primary outcome was cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version (ADAS-Cog-C). The secondary outcome was self-care as measured by the activities of daily living scale (ADL) and changes in plasma metabolites. RESULTS: This study showed a significant (p < 0.01) reduction in ADAS-Cog-C scores between the MCT (2.62 points below baseline) and placebo interventions (2.57 points above baseline). Data from 46 (86.8%) APOE4-/- subjects who completed the entire study were analyzed. Changes in ADL scores were not significantly different between the MCT and placebo interventions (p > 0.05). The concentrations of TC, HDL-C, ß-hydroxybutyrate and acetoacetate were significantly higher in the MCT group than in the placebo group (p < 0.05). Lysophosphatidylcholine 16:0 (LysoPC (16:0)), LysoPC (P-18:0), LysoPC (P-18:1(9Z)), LysoPC (20:2(11Z,14Z)), and LysoPC (22:5(4Z,7Z,10Z,13Z,16Z)) were significantly increased after MCT intervention, and the concentrations of LysoPC (18:0), palmitic acid, linoleic acid, oleic acid, and 7,12-dimethylbenz[a]anthracene were significantly decreased (p < 0.05), whereas no significant changes appeared after the placebo intervention. Androstenedione concentration increased after placebo intervention. Furthermore, a significant negative correlation was observed between changes in LysoPC (P-18:1(9Z)) and ADAS-Cog-C scores after MCT intervention (r = -0.1472, p < 0.05). CONCLUSIONS: MCT had positive effects on cognitive ability in mild to moderate AD patients with APOE4-/-. These effects of MCT might be related to the metabolism of LysoPC, oleic acid, linoleic acid and palmitic acid, in addition to the ketogenic effect. STUDY ID NUMBER: ChiCTR-IOR-16009737. REGISTRY WEBSITE: WHO ICTRP Search Portal - http://apps.who.int/trialsearch/Default.aspx.

Caprylic acid suppresses inflammation via TLR4/NF-κB signaling and improves atherosclerosis in ApoE-deficient mice.

BACKGROUND: As reported previously by our group, medium-chain triglycerides can ameliorate atherosclerosis. Given that TLR4 is closely related to atherosclerosis, we hypothesized herein that caprylic acid (C8:0) would suppress inflammation via TLR4/NF-κB signaling and further promote the amelioration of atherosclerosis in apoE- deficient (apoE-/-) mice. METHODS: Fifty 6-week male apoE-/- mice were randomly allocated into five diet groups: a high-fat diet (HFD) without or with 2% caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0), or linolenic acid (C18:3). RAW246.7 cells were treated with caprylic acid (C8:0), docosahexenoic acid (DHA), palmitic acid (C16:0), and lipopolysaccharide (LPS) with or without TLR4 knock-down (TLR4-KD). The serum lipid profiles, inflammatory biomolecules, and mRNA and protein expression levels were measured. Atherosclerotic lesions that occurred in the aorta and aortic sinuses were evaluated and quantified. RESULTS: Our results indicated that C8:0 reduced body fat, improved the lipid profiles, suppressed inflammatory cytokine production, downregulated aortic TLR4, MyD88, NF-κB, TNF-α, IKKα, and IKKß mRNA expression, and alleviated atherosclerosis in the apoE-/- mice (P < 0.05). In RAW 264.7 cells, C8:0 diminished the inflammatory response and both mRNA and protein expression of TLR4, MyD88, NF-κB, and TNF-α compared to those in the LPS and C16:0 groups (P < 0.05). However, in the TLR4-KD RAW 264.7 cells, C8:0 significantly upregulated NF-κB mRNA and protein expression compared to those in the C16:0 and DHA groups. CONCLUSIONS: These results suggest that C8:0 functions via TLR4/NF-κB signaling to improve the outcomes of apoE-/- mice through suppressing inflammation and ameliorating atherosclerosis. Thus, C8:0 may represent as a promising nutrient against chronic inflammatory diseases.

Medium-chain fatty acids decrease serum cholesterol via reduction of intestinal bile acid reabsorption in C57BL/6J mice.

BACKGROUND: Bile acids play a pivotal role in cholesterol metabolism via the enterohepatic circulation. This study investigated the effects of medium-chain triglycerides (MCTs)/medium-chain fatty acids (MCFAs) on the reduction of bile acid absorption in the small intestine and the mechanisms of action in vivo and partially verified in vitro. METHODS: Thirty-six C57BL/6 J mice with hypercholesterolaemia were randomly divided into 3 groups: fed a cholesterol-rich diet (CR group), fed a cholesterol-rich and medium-chain triglyceride diet (CR-MCT group) and fed a cholesterol-rich and long-chain triglyceride diet (CR-LCT group). Body weights and blood lipid profiles were measured in all groups after 16 weeks of treatment. The concentrations of bile acids in bile and faeces were analysed using HPLC-MS (high-performance liquid chromatography-mass spectrometry). Gene transcription and the expression levels associated with bile acid absorption in the small intestines were determined using real-time PCR and Western blot. Ileal bile acid binding protein (I-BABP) was analysed using immunofluorescence. The effects of MCFAs on the permeability of bile acid (cholic acid, CA) in Caco-2 cell monolayers and I-BABP expression levels in Caco-2 cells treated with caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0) and oleic acid (C18:1) were determined. RESULTS: Mice in the CR-MCT group exhibited lower body weights and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and a higher HDL-C/LDL-C ratio than the CR-LCT group (P < 0.05). The concentrations of primary bile acids (primarily CA) and secondary bile acids in faeces and secondary bile acids in bile in the CR-MCT group were significantly higher than in the CR-LCT group (P < 0.05). C8:0 and C10:0 decreased the permeability of CA in Caco-2 cell monolayers. MCT/MCFAs (C8:0 and C10:0) inhibited I-BABP gene expression in the small intestines and Caco-2 cells (P < 0.05). CONCLUSIONS: MCT slowed the body weight increase and promoted the excretion of bile acids. MCT lowered serum cholesterol levels at least partially via reduction of bile acid absorption in the small intestine by inhibition of I-BABP expression. Our results provide the basis for clinical trials of MCT as a dietary supplement for lowering plasma cholesterol and reducing risk of CHD.

[Effects of caprylic acid, capric acid or stearic acid on exogenous cholesterol absorption in intestine of ApoE~(-/-) mice].

OBJECTIVE: To investigate caprylic acid( C8 ∶ 0), capric acid( C10 ∶ 0)or stearic acid( C18∶ 0) on the absorption of exogenous cholesterol in mice. METHODS: ApoE-/-mice were randomly divided into 3 groups: 2% caprylic acid( C8 ∶ 0), capric acid( C10∶ 0) or stearic acid( C18∶ 0) were fed with high cholesterol diet for 16 weeks. Serum lipids and lipoproteins were measured at the beginning of the experiment, the 8 th week and the 16 th week. At 16 th weeks of intervention, 1 h and 4 h after ~3H-cholesterol intragastric administration, the contents of ~3H-cholesterol in the jejunum, ileum and colon contents of mice were intragastric measured. Also the levels of ~3H-cholesterol in blood of0. 5 h, 1 h, 2 h and 4 h after administration were measured. RESULTS: Serum TC and LDL-c in the C8∶ 0 group were significantly lower than those in the C18: 0 group at the 8 th week of intervention( P < 0. 01). Serum TC and LDL-c levels of the both C8∶ 0 group and C10∶ 0 group were significantly lower than those in the C18 ∶ 0 group at the 16 th week( P < 0. 01). The contents of ~3H-cholesterol in the jejunum of mice in C8 ∶ 0 group were significantly lower than those in C18 ∶ 0 group after 1 h of ~3H-cholesterol intragastric administration( P < 0. 05). The contents of ~3H-cholesterol in the colon contents of mice in C8∶ 0 group were significantly higher than those in C18∶ 0 group after 1 h( P < 0. 05) and4 h( P < 0. 01) of ~3H-cholesterol intragastric administration. The ~3H-cholesterol content in blood in C8∶ 0 group were significantly lower than those in C18∶ 0 group after 0. 5 h and 2 h of intragastric administration( P < 0. 01). And the area under the curve( AUC) of ~3H-cholesterol in blood after 4 h of intragastric administration in C8∶ 0 group were significantly lower than those in C18 ∶ 0 group( P < 0. 05). CONCLUSION: Caprylic acid could reduce the absorption of exogenous cholesterol in the intestinal tract and improve blood cholesterol metabolism of mice.

[Effects of medium-chain fatty acids on high-density-lipoprotein in rats fed with high fat diet].

OBJECTIVE: To explore the effects of medium-chain fatty acid( MCFA) on high-density-lipoprotein( HDL) in serum, liver and small intestine in Sprague Dawley rats fed with high fat diet. METHODS: Thirty obese rats were divided into 3 groups randomly, and were fed high fat diet mixed with 2% octanoic acid, 2% decanoic acid, 2% oleic acid respectively for 8 weeks. The levels of blood HDL, apolipoprotein A1( ApoA1), apolipoprotein A2( ApoA2), triglyceride( TG), total cholesterol( TC), high-densitylipoprotein cholesterol( HDL-c), low-density lipoprotein cholesterol( HDL-c) in serum were measured at the fourth and eighth week. The levels of HDL, ApoA1, and ApoA2 in liver and small intestine were measured by ELISA. Real-time PCR was used to detect the mRNA expression of ApoA1 and ApoA2 in liver and small intestine from rats at the eighth week. RESULTS: At the eighth week, significant decreases in levels of serum TG and TC were observed in octanoic acid and decanoic acid groups as compared with oleic acid group( P < 0. 05). Greater increases in levels of serum HDL and HDL-c/LDL-c were observed in octanoic acid group than in oleic acid group( P < 0. 05). Greater increases in protein expression of HDL and ApoA1 and in mRNA expression of ApoA1 in small intestine were observed in octanoic acid group than in oleic acid group( P < 0. 05). CONCLUSION: MCFA can elevate the levels of HDL, HDL-c/LDL-c in serum, and increase the expressions of HDL and ApoA1 in small intestine.

Medium-chain fatty acids reduce serum cholesterol by regulating the metabolism of bile acid in C57BL/6J mice.

Hypercholesterolemia is one of the important risk factors of atherosclerosis (AS). The aim of this study is to explore the effect of medium-chain fatty acids (MCFAs) on serum cholesterol levels and their mechanism of action. Hyperlipemia, as a model of abnormal lipid hypermetabolism, was established by using a high fat diet in C57BL/6J mice. Forty eight mice with dyslipidemia were randomly divided into 4 groups, 12 mice per group, including the control group, the 2% caprylic acid (C8:0)-treated group, 2% capric acid (C10:0)-treated group, and 2% oleic acid (C18:1)-treated group. All mice were fed with a high fat diet. After 16 weeks, the mice were anesthetized with chloral hydrate. The mouse portal vein blood, the liver and the start site of the ileum (1 cm) were collected. The body weight of the mice and blood lipid profiles were measured. Gene transcription and the expression level associated with bile acid metabolism in the liver and small intestine were determined by real-time PCR and the western blotting method. The concentrations of bile acid metabolites in bile and feces were analysed. After 16 weeks of treatment, the concentrations of TC and LDL-C in the caprylic acid group were significantly lower than those in the control group (P < 0.05); the transcription and expression level of LXR, CYP7A1, CYP27A1 and ABCG8 in the caprylic acid and capric acid groups were significantly higher than those in the control group in the liver (P < 0.05), however the transcription and expression level of the small heterodimer partner (SHP) were significantly lower than those in the control group (P < 0.05); the transcription and expression level of LXR, ABCG5 and ABCG8 in the caprylic acid, capric acid and oleic acid groups were significantly higher than those in the control group in the small intestine (P < 0.05). The concentrations of total bile acid, mainly cholic acid and cholesterol in bile and feces were significantly higher in the caprylic and capric acid groups than those of in the control group (P < 0.05). Thus, MCFA increased the expression of LXR and ABCG8, enhanced CYP7A1 and CYP27A1 expression, decreased and SHP expression in the liver, thereby promoted liver bile acid synthesis and excretion. In addition MCFA increased the expression of ABCG5, ABCG8 and LXR in the small intestine, thereby inhibiting small intestinal bile acid absorption, increasing the concentrations of cholesterol and bile acid in bile and feces and reducing the level of serum cholesterol.

Medium-chain triglycerides promote macrophage reverse cholesterol transport and improve atherosclerosis in ApoE-deficient mice fed a high-fat diet.

We previously observed that medium-chain triglycerides (MCTs) could reduce body fat mass and improve the metabolism of cholesterol. We hypothesized that MCTs can improve atherosclerosis by promoting the reverse cholesterol transport (RCT) process. Therefore, the objective of this study was to investigate the roles of MCTs in macrophage RCT and the progression of atherosclerosis. To test this hypothesis, 30 4-week-old ApoE-deficient (ApoE(-/-)) mice were randomly divided into 2 groups and fed a diet of 2% MCTs or long-chain triglycerides (LCTs) for 16 weeks. Ten age- and sex-matched C57BL/6J mice were fed a diet of 2% LCTs as the control. Macrophage-to-feces RCT was assessed in vivo by intraperitoneal injection of RAW 264.7 macrophages containing (3)H-labeled cholesterol, and atherosclerotic plaques were measured. The mRNA and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. There was a greater decrease in body fat mass, atherosclerotic plaques, and an improvement in serum lipid profiles. In addition, the MCT mice group showed an increase in (3)H-tracer in the feces and a decrease in the liver. Significantly higher levels of mRNA and protein expression of hepatic ATP-binding cassette transporter A1, ATP-binding cassette transporter G5, cholesterol 7α-hydroxylase, and intestinal ATP-binding cassette transporter G8, as well as lower levels of expression of intestinal Niemann-Pick C1-like 1, were found in the MCT group. These results suggest that MCTs could obviously promote macrophage RCT and improve atherosclerosis in ApoE(-/-) mice, indicating that MCTs have the potential to prevent cardiovascular disease.

[Efficacy analysis of laparoscopic adjustable gastric placation for obesity].

OBJECTIVE: To analyze the efficacy and safety of laparoscopic adjustable gastric placation (LAGBP), a new procedure for surgical treatment of obesity. METHODS: Clinical and 1-year follow-up data of 10 patients who underwent LAGBP in our department between September and November 2011 were analyzed retrospectively. RESULTS: The mean operative time was (93.0±13.4) min, while the mean intraoperative blood loss was (15.5±4.7) ml. The mean excessive body weight loss rate(%EWL) at 3, 6, 9 and 12 months after the operation was 25.1%, 40.6%, 45.3% and 50.8% respectively. There were no severe post operative complications. CONCLUSIONS: LAGBP is associated with high safety and good short-term efficacy.

[Effects of teaseed oil on triglyceride and weight in hypertriglyceridemic subjects].

OBJECTIVE: To investigate the effects of teaseed oil on triglyceride and weight in hypertriglyceridemic subjects. METHODS: Twenty-five hypertriglyceridemic subjects were enrolled in the study. All subjects were required to ingest 25-30 g/d of the teaseed oil as cooking oil for 8 consecutive weeks. The height, body weight, BMI and the serum oleic acid (OA), total triglyceride (TG) , total cholesterol (TC) , blood glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in hypertriglyceridemic subjects were measured. The daily total energy, macronutrients intake and activity level were recorded at the beginning and ending of the study. RESULTS: Twenty-one subjects completed the study. As compared to data at the beginning, the levels of OA in serum and dietary intakes of OA, monounsaturated fatty acids significantly increased. Polyunsaturated fatty acids intake and body weight, BMI decreased significantly. CONCLUSION: Teaseed oil could increase the serum levels of OA and reduce weight and BMI in the hypertriglyceridemic subjects with stable dietary intake and exercise.

Medium-chain fatty acids enhanced the excretion of fecal cholesterol and cholic acid in C57BL/6J mice fed a cholesterol-rich diet.

The objective of the present study was to investigate the cholesterol-reducing effect of medium-chain fatty acids (MCFAs) completed by elevated excretion of fecal neutral steroids and/or bile acids. Blood and liver lipid profiles, fecal neutral steroids, bile acids, and mRNA and protein expression of the genes relevant to cholesterol homeostasis were measured and analyzed in C57BL/6J mice fed a cholesterol-rich diet with 2% caprylic acid or capric acid for 12 weeks. Blood total cholesterol and low-density lipoprotein cholesterol (LDL-c) levels were reduced significantly as compared to diet with palmitic acid or stearic acid. Caprylic acid promoted the excretion of fecal neutral steroids, especially cholesterol. The excretion of fecal bile acids, mainly in the form of cholic acid was enhanced and accompanied by elevated expression of mRNA and the protein of hepatic cholesterol 7α-hydroxylase (CYP7A1). These results indicate that MCFAs can reduce blood cholesterol by promoting the excretion of fecal cholesterol and cholic acid.

A tripeptide Diapin effectively lowers blood glucose levels in male type 2 diabetes mice by increasing blood levels of insulin and GLP-1.

The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Effective therapies, such as insulin and Glucagon-like peptide-1 (GLP-1), require injections, which are costly and result in less patient compliance. Here, we report the identification of a tripeptide with significant potential to treat T2D. The peptide, referred to as Diapin, is comprised of three natural L-amino acids, GlyGlyLeu. Glucose tolerance tests showed that oral administration of Diapin effectively lowered blood glucose after oral glucose loading in both normal C57BL/6J mice and T2D mouse models, including KKay, db/db, ob/ob mice, and high fat diet-induced obesity/T2D mice. In addition, Diapin treatment significantly reduced casual blood glucose in KKay diabetic mice in a time-dependent manner without causing hypoglycemia. Furthermore, we found that plasma GLP-1 and insulin levels in diabetic models were significantly increased with Diapin treatment compared to that in the controls. In summary, our findings establish that a peptide with minimum of three amino acids can improve glucose homeostasis and Diapin shows promise as a novel pharmaceutical agent to treat patients with T2D through its dual effects on GLP-1 and insulin secretion.

[Effects of oils on lipid metabolism in obese C57BL/6J mice induced by a high fat diet].

OBJECTIVE: To investigate and compare the effects of oils on lipid metabolism in obese C57BL/6J fed a high fat diet. METHODS: 75 male C57BL/6J mice (4-5 weeks old) were used and randomly divided into 5 groups, 15 mice in each group, and were fed a high fat diets with 2% soybean oil, medium-chain triglyceride (MCT), peanut oil, olive oil and tea seed oil respectively for 12 weeks. Body weight, body fat, diet intake, blood lipid profiles and enzymes relevant to lipid metabolism in white adipose tissue (WAT) as well as pathologic changes in WAT and livers from all groups were observed and compared. RESULTS: At the end of study, the body weight and body fat weight were significantly lower in MCT, peanut oil, olive oil, tea oil groups than in soybean oil group (P < 0.05). The mice in MCT group showed significantly lower TG, TC, LDL-C in serum and lower TG, TC in liver than those in soybean oil group (P < 0.05). The cAMP, PKA, HSL, ATGL in WAT in MCT group showed higher than those in soybean oil group (P < 0.05). There was no fatty infiltration in the livers of mice fed MCT, olive oil and tea oil group, but visible fatty liver in soybean oil and peanut oil group were found. CONCLUSION: Compared to soybean oil, MCT, peanut oil, olive oil and tea oil could reduce body weight and body fat weight in obese mice fed a high fat diet, MCT also decreased TG, TC, LDL-C in serum and promote lipid mobilization in WAT. As to improving blood lipids, olive oil and tea oil were less obvious than MCT was, and both oils did not induce significant fatty liver when compared with soybean oil and peanut oil.

Increased norepinephrine by medium-chain triglyceride attributable to lipolysis in white and brown adipose tissue of C57BL/6J mice.

A further investigation of the lipolysis induced by medium-chain triglyceride (MCT) was conducted on C57BL/6J mice fed with a diet containing 2% MCT or 2% long-chain triglyceride (LCT). Blood norepinephrine, body fat and blood lipid variables, and the protein or mRNA expression of the genes relevant to lipolysis were measured and analyzed in the white and brown adipose tissue (WAT, BAT). Decreased body fat and improved blood lipid profiles attributable to MCT were confirmed. A higher level of blood norepinephrine was observed with the MCT diet. The adipose triglyceride lipase (ATGL) activity and its mRNA expression, the expression of protein and mRNA of the beta 3 adrenergic receptor (ß3-AR) in both WAT and BAT, and the hormone-sensitive lipase (HSL) activity and its mRNA expression in BAT were significantly increased in the mice with MCT feeding. The lipolysis induced by MCT might be partially mediated by increasing norepinephrine, thereafter signaling the up-regulation of ß3-AR, ATGL, and HSL in WAT and BAT.

[Hydrolysis method for whey protein and the hypoglycemic activity of its peptides in diabetic KKAy mice].

OBJECTIVE: To explore the hydrolysis method for whey protein with alkaline proteinase, and to investigate the hypoglycemic activity of the peptides in diabetic KKAy mice. METHODS: Whey protein was hydrolyzed with alkaline proteinase, and the degree of hydrolysis, nitrogen and amino acid content, mass spectrographic analysis of the peptides were determined. Changes of fasting blood glucose, random blood glucose, glucose tolerance and insulin levels in diabetic KKAy mice were measured after the peptides were given by gavage. RESULTS: The degree of hydrolysis of whey protein was 14.8%, the nitrogen in the peptides was 68.2%, and the molecular weight of the peptides was 900 - 1900 Dal, mostly was 1800 - 1900 Dal. Blood glucose of KKAy mice was decreased at 0.5 and 1 h after oral injection of the peptides, and insulin level was increased at 0.5 h after ingestion of the peptides. CONCLUSION: Fasting blood glucose and random blood glucose levels of type 2 diabetic KKAy mice could be significantly decreased, and the glucose tolerance and insulin secretion of mice could be improved by whey protein peptides.

Triglyceride with medium-chain fatty acids increases the activity and expression of hormone-sensitive lipase in white adipose tissue of C57BL/6J mice.

We have previously shown that medium-chain triglyceride (MCT) resulted in significantly less body fat mass than long-chain triglyceride (LCT) did in hypertriglyceridimic subjects. The possible mechanism for this was investigated by measuring and analyzing changes in the body fat, blood lipid profile, enzymatic level and activity of hormone-sensitive lipase (HSL) and its mRNA expression, and levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in white adipose tissue (WAT) of C57BL/6J mice fed for 16 weeks on an MCT or LCT diet. MCT induced lower body weight and body fat, and an improved blood lipid profile than LCT did. The enzymatic level and activity of HSL and its mRNA expression, and the levels of cAMP and PKA were significantly higher in WAT of mice fed with the MCT diet. No significant differences in the levels of lipoprotein lipase and peroxisome proliferator-activated receptor-γ in WAT were apparent between the effects of MCT and LCT. It is concluded that lipolysis by the increased level and activity of HSL, which was induced by the activation of cAMP-dependent PKA in WAT, was partially responsible for the lower fat accumulation in C57BL/6J mice fed with MCT.

Micronutrients decrease incidence of common infections in type 2 diabetic outpatients.

A randomized, double-blind, placebo-controlled trial was carried out to investigate the effects of micronutrients supplementation on immunity and the incidence of common infections in type 2 diabetic outpatients. A total of 196 type 2 diabetic outpatients were randomized to receive tablets of micronutrients (n=97) or placebo (n=99) for 6 months. Individualized dietary energy intake and daily physical activity were recommended. Anthropometric measurements, blood biochemical variables and the incidence of common infections were measured at baseline and at 6 months. Data on diet, exercise and infection (upper respiratory tract infection, skin infection, urinary and genital tract infections, other infections) were recorded 1 month before the study and every month during the study. Blood concentrations of total protein, iron (Fe), folic acid and hemoglobin increased and unsaturated iron-binding capacity(UIBC) levels were decreased in the micronutrients supplementation group compared to the placebo group at 6 months. Moreover, at 6 months, compared to the placebo group, the blood concentrations of IgE, CD4+, CD4+/CD8+, WBC, lymphocyte counts, basophilic leukocyte increased and CD8+ count decreased in the supplementation group, and the levels of IgA, IgM, IgG and complements C3 and C4 did not differ. The incidence of upper respiratory infection, whitlow, dermapostasis, vaginitis, urinary tract infection, gingivitis and dental ulcer were lower and body temperature and duration of fever greatly improved in the supplementation than the placebo group. These data indicated that supplementation of micronutrients might increase immune function and reduce the incidence of common infections in type 2 diabetic outpatients.

[Changes of caspase-9 in rat retina caused by Nd:YAG laser injury].

OBJECTIVE: To investigate the changes of caspase-9 in the retina of Long Evans rats caused by Nd: YAG laser injury. METHODS: A model of retina injury in rats caused by Nd:YAG laser was established. The activity and the expression of mRNA and protein of caspase-9 were detected at Oh, 3h, 6h, 24h, 3d and 7d after laser irradiation. RESULTS; No conspicuous change of caspase-9 mRNA in retina was observed just after laser irradiation, but the activity of caspase-9 and the expression of caspase-9 mRNA and protein increased significantly at 6h and 12h after irradiation (P < 0.05). CONCLUSION: Caspase-9 in the retina of LE rat was activated by Nd:YAG laser irradiation.

[Effects of 9,10-dihydroxysteatic acid on glucose metabolism in KKAy mice].

OBJECTIVE: To study the effect of 9,10-dihydroxystearic acid (DHSA) on glucose tolerance and insulin sensitivity in KKAy diabetic mice. METHODS: 48 male KKAy mice were randomly divided into four groups and were fed with high fat diet containing 4% DHSA, 2% DHSA, 4% Olive oil and 4% Corn oil, respectively. Glucose tolerance and insulin sensitivity were measured after 5 and 6 weeks respectively. Effects of DHSA on activating PPAR-alpha and PPAR-gamma in CV-1 cells were also carried out. RESULTS: In glucose tolerance test, the blood glucose at 0.5 h and 1 h and the area under glucose curve in the group fed with 4% DHSA diet were significantly lower than those of other groups. In insulin sensitivity test, the blood glucose level at 0.5 h and 1 h after injection of insulin was lower in the 4% DHSA diet group, indicating the insulin sensitivity of this group was obviously higher than other groups (P < 0.05). The body weight of the mice fed with 4% DHSA diet was much lower than those mice fed with 4% Corn diet (P < 0.05). 5 - 20 micromol/L DHSA did not activate PPAR-gamma in CV-1 cells but 50 - 100 micromol/L DHSA activated PPARgamma in a dose-dependent way although the activating effect of DHSA on PPARgamma was significantly lower than that of rosiglitazone. DHSA did not activate PPAR-alpha in CV-1 cells. CONCLUSION: DHSA may improve glucose tolerance and insulin sensitivity in KKAy mice and the effect might be related to the activation of PPAR-gamma by DHSA.