SCOPE:: Hypothalamic astrogliosis and inflammation cause neural injury, playing a critical role in metabolic syndrome development. This study investigated whether and how fructose caused hypothalamic astrogliosis and inflammation in vivo and in vitro. The inhibitory effects of betaine on hypothalamic neural injury, astrogliosis and inflammation were explored to address its improvement of fructose-induced metabolic syndrome.
METHODS AND RESULTS:: Rats or astrocytes were exposed to fructose and then treated with betaine. Neural injury, proinflammatory markers, toll-like receptor 4/nuclear factor-kappaB (TLR4/NF-kappaB) pathway and histone deacetylases (HDAC3) expression were evaluated. The reduction of pro-opiomelanocortin (POMC) and melanocortin 4 receptor (Mc4R) neurons in fructose-fed rats were ameliorated by betaine. Moreover, fructose induced astrogliosis and proinflammatory cytokines by increasing TLR4, MyD88 and NF-kappaB expression in rat hypothalamus and astrocytes. HDAC3 over-expression preserved the prolonged inflammation in fructose-stimulated astrocytes by regulating nuclear NF-kappaB-dependent transcription. Betaine suppressed TLR4/NF-kappaB pathway activation and HDAC3 expression, contributing to its inhibition of hypothalamic astrogliosis and inflammation in animal and cell models.
CONCLUSION:: These findings suggest that betaine inhibits fructose-caused astrogliosis and inflammation by the suppression of TLR4/NF-kappaB pathway activation and HDAC3 expression to protect against hypothalamic neural injury, which, at least partly, contributes to the improvement on fructose-induced metabolic syndrome.
Li, J.M., et al., Betaine recovers hypothalamic neural injury by inhibiting astrogliosis and inflammation in fructose-fed rats. Mol Nutr Food Res, 2014
Thursday, October 16, 2014
Higher serum concentrations of betaine is associated with better profiles of body fat and fat distribution in Chinese adults
Objective: Animal studies have suggested that betaine but not choline may improve body composition, but little evidence is available in humans. We examined the associations of serum concentrations of choline and betaine with body composition and fat distribution in adults.
Methods: This community-based study recruited 1996 adults (W/M: 1380/616) aged 40-75 in urban Guangzhou, China. General information and anthropometric measurements were taken, and serum choline and betaine levels were assessed by HPLC-MS between July 2008 and June 2010. After 3.2 years, 1623 of the 1996 participants were measured for fat mass (FM and %FM) over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions. The %FM ratios of the A/G and the trunk and limbs were determined by dual-energy X-ray absorptiometry (DXA).
Results: Univariate analyses showed that higher serum betaine levels were significantly associated with lower values of adiposity indices, except in the case of the %FM at the gynoid area. After adjusting for potential covariates, similar associations were observed. The mean percentage differences between quartiles 4 and 1 of the serum betaine levels were -4.9% (weight), -4.7% (BMI), -2.5% (WC), -7.9% (TB FM) and -3.4% (TB %FM). The mean differences in the FM and %FM were much more pronounced at the trunk (-10.0% and -4.5%) or android areas (-10.7% and -4.7%) than those at the limbs (-0.8% and -2.3%) or gynoid areas (-0.6% and -1.4%). Such favorable associations were stronger in men than in women. No significant associations between serum choline and the adiposity indices were observed, except in the cases of body weight and BMI.
Conclusions: Greater circulating betaine, but not choline, was dose-dependently associated with better body composition and fat distribution due to a lower fat mass in the trunk regions in this population.
Chen, Y.-m., et al., Higher serum concentrations of betaine rather than choline is associated with better profiles of DXA-derived body fat and fat distribution in Chinese adults. Int J Obes, 2014.
Methods: This community-based study recruited 1996 adults (W/M: 1380/616) aged 40-75 in urban Guangzhou, China. General information and anthropometric measurements were taken, and serum choline and betaine levels were assessed by HPLC-MS between July 2008 and June 2010. After 3.2 years, 1623 of the 1996 participants were measured for fat mass (FM and %FM) over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions. The %FM ratios of the A/G and the trunk and limbs were determined by dual-energy X-ray absorptiometry (DXA).
Results: Univariate analyses showed that higher serum betaine levels were significantly associated with lower values of adiposity indices, except in the case of the %FM at the gynoid area. After adjusting for potential covariates, similar associations were observed. The mean percentage differences between quartiles 4 and 1 of the serum betaine levels were -4.9% (weight), -4.7% (BMI), -2.5% (WC), -7.9% (TB FM) and -3.4% (TB %FM). The mean differences in the FM and %FM were much more pronounced at the trunk (-10.0% and -4.5%) or android areas (-10.7% and -4.7%) than those at the limbs (-0.8% and -2.3%) or gynoid areas (-0.6% and -1.4%). Such favorable associations were stronger in men than in women. No significant associations between serum choline and the adiposity indices were observed, except in the cases of body weight and BMI.
Conclusions: Greater circulating betaine, but not choline, was dose-dependently associated with better body composition and fat distribution due to a lower fat mass in the trunk regions in this population.
Chen, Y.-m., et al., Higher serum concentrations of betaine rather than choline is associated with better profiles of DXA-derived body fat and fat distribution in Chinese adults. Int J Obes, 2014.
Carnitine, erythritol and betaine may have efficacy in reducing innate inflammation in dry eye disease.
Purpose: To explore the effects of osmoprotectants on pro-inflammatory mediator production in primary human corneal epithelial cells (HCECs) exposed to hyperosmotic stress.
Methods: HCECs cultured in iso-osmolar medium (312 mOsM) were switched to hyperosmotic media with or without prior incubation with 2-20 mM of l-carnitine, erythritol or betaine for different time periods. The mRNA expression and protein production of pro-inflammatory markers in HCECs were evaluated by RT-qPCR and ELISA.
Results: Hyperosmolar media significantly stimulated the mRNA and protein expression of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, and chemokines, IL-8, CCL2 and CCL20 in HCECs in an osmolarity dependent manner. The stimulated expression of these pro-inflammatory mediators was significantly but differentially suppressed by l-carnitine, erythritol or betaine. l-Carnitine displayed the greatest inhibitory effects and down-regulated 54-77% of the stimulated mRNA levels of TNF-alpha (down from 12.3-5.7 fold), IL-1beta (2.2-0.9 fold), IL-6 (7.3-2.9 fold), IL-8 (4.6-2.0 fold), CCL2 (15.3-3.5 fold) and CCL20 (4.1-1.5 fold) in HCECs exposed to 450 mOsM. The stimulated protein production of TNF-alpha, IL-1beta, IL-6 and IL-8 was also significantly suppressed by l-carnitine, erythritol and betaine. l-carnitine suppressed 49-79% of the stimulated protein levels of TNF-alpha (down from 81.3 to 17.4 pg/ml), IL-1beta (56.9-29.2 pg/ml), IL-6 (12.8-4.6 ng/ml) and IL-8 (21.2-10.9 ng/ml) by HCECs exposed to 450 mOsM. Interestingly, hyperosmolarity stimulated increase in mRNA and protein levels of TNF-alpha, IL-1beta and IL-6 were significantly suppressed by a transient receptor potential vanilloid channel type 1 (TRPV1) activation inhibitor capsazepine.
Conclusions: l-carnitine, erythritol and betaine function as osmoprotectants to suppress inflammatory responses via TRPV1 pathway in HCECs exposed to hyperosmotic stress. Osmoprotectants may have efficacy in reducing innate inflammation in dry eye disease.
Hua, X., et al., Effects of l-Carnitine, Erythritol and Betaine on Pro-inflammatory Markers in Primary Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress. Curr Eye Res, 2014: p. 1-11.
Methods: HCECs cultured in iso-osmolar medium (312 mOsM) were switched to hyperosmotic media with or without prior incubation with 2-20 mM of l-carnitine, erythritol or betaine for different time periods. The mRNA expression and protein production of pro-inflammatory markers in HCECs were evaluated by RT-qPCR and ELISA.
Results: Hyperosmolar media significantly stimulated the mRNA and protein expression of pro-inflammatory cytokines, TNF-alpha, IL-1beta and IL-6, and chemokines, IL-8, CCL2 and CCL20 in HCECs in an osmolarity dependent manner. The stimulated expression of these pro-inflammatory mediators was significantly but differentially suppressed by l-carnitine, erythritol or betaine. l-Carnitine displayed the greatest inhibitory effects and down-regulated 54-77% of the stimulated mRNA levels of TNF-alpha (down from 12.3-5.7 fold), IL-1beta (2.2-0.9 fold), IL-6 (7.3-2.9 fold), IL-8 (4.6-2.0 fold), CCL2 (15.3-3.5 fold) and CCL20 (4.1-1.5 fold) in HCECs exposed to 450 mOsM. The stimulated protein production of TNF-alpha, IL-1beta, IL-6 and IL-8 was also significantly suppressed by l-carnitine, erythritol and betaine. l-carnitine suppressed 49-79% of the stimulated protein levels of TNF-alpha (down from 81.3 to 17.4 pg/ml), IL-1beta (56.9-29.2 pg/ml), IL-6 (12.8-4.6 ng/ml) and IL-8 (21.2-10.9 ng/ml) by HCECs exposed to 450 mOsM. Interestingly, hyperosmolarity stimulated increase in mRNA and protein levels of TNF-alpha, IL-1beta and IL-6 were significantly suppressed by a transient receptor potential vanilloid channel type 1 (TRPV1) activation inhibitor capsazepine.
Conclusions: l-carnitine, erythritol and betaine function as osmoprotectants to suppress inflammatory responses via TRPV1 pathway in HCECs exposed to hyperosmotic stress. Osmoprotectants may have efficacy in reducing innate inflammation in dry eye disease.
Hua, X., et al., Effects of l-Carnitine, Erythritol and Betaine on Pro-inflammatory Markers in Primary Human Corneal Epithelial Cells Exposed to Hyperosmotic Stress. Curr Eye Res, 2014: p. 1-11.
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