Flavonoids are important natural compounds with diverse biologic activities. Citrus flavonoids constitute an important series of flavonoids. Naringin and its aglycone naringenin belong to this series of flavonoids and were found to display strong anti-inflammatory and antioxidant activities. Several lines of investigation suggest that naringin supplementation is beneficial for the treatment of obesity, diabetes, hypertension, and metabolic syndrome. A number of molecular mechanisms underlying its beneficial activities have been elucidated. However, their effect on obesity and metabolic disorder remains to be fully established. Moreover, the therapeutic uses of these flavonoids are significantly limited by the lack of adequate clinical evidence. This review aims to explore the biologic activities of these compounds, particularly on lipid metabolism in obesity, oxidative stress, and inflammation in context of metabolic syndrome.

The ketone body b-hydroxybutyrate (BHB) is an endogenous factor protecting against stroke and neurodegenerative diseases, but its mode of action is unclear. Here we show in a stroke model that the hydroxy-carboxylic acid receptor 2 (HCA 2 , GPR109A) is required for the neuroprotective effect of BHB and a ketogenic diet, as this effect is lost in Hca2 À / À mice. We further demonstrate that nicotinic acid, a clinically used HCA 2 agonist, reduces infarct size via a HCA 2 -mediated mechanism, and that noninflammatory Ly-6C Lo monocytes and/or macrophages infiltrating the ischemic brain also express HCA 2 . Using cell ablation and chimeric mice, we demonstrate that HCA 2 on monocytes and/or macrophages is required for the protective effect of nicotinic acid. The activation of HCA 2 induces a neuroprotective phenotype of monocytes and/or macrophages that depends on PGD 2 production by COX1 and the haematopoietic PGD 2 synthase. Our data suggest that HCA 2 activation by dietary or pharmacological means instructs Ly-6C Lo monocytes and/or macrophages to deliver a neuroprotective signal to the brain.

Taken orally, the drug dimethyl fumarate (DMF) has been shown to improve functional outcomes for patients with MS; however, it is unclear how DMF mediates a protective effect. DMF and, more so, its active metabolite, monomethyl fumarate, are known agonists of the hydroxycarboxylic acid receptor 2 (HCA 2 ), a G proteincoupled membrane receptor. Here, we evaluated the contribution of HCA 2 in mediating the protective effect afforded by DMF in EAE, a mouse model of MS. DMF treatment reduced neurological deficit, immune cell infiltration, and demyelination of the spinal cords in wild-type mice, but not in Hca2 -/-mice, indicating that HCA 2 is required for the therapeutic effect of DMF. In particular, DMF decreased the number of infiltrating neutrophils in a HCA 2 -dependent manner, likely by interfering with neutrophil adhesion to endothelial cells and chemotaxis. Together, our data indicate that HCA 2 mediates the therapeutic effects of DMF in EAE. Furthermore, identification of HCA 2 as a molecular target may help to optimize MS therapy.

No abstract

Hydroxycinnamic acid derivatives are important class of polyphenolic compounds originated from the Mavolanate-Shikimate biosynthesis pathways in plants. Several simple phenolic compounds such as cinnamic acid, p-coumaric acid, ferulic acid, caffeic acid, chlorgenic acid, and rosmarinic acid belong to this class. These phenolic compounds possess potent antioxidant and anti-inflammatory properties. These compounds were also showed potential therapeutic benefit in experimental diabetes and hyperlipidemia. Recent evidences also suggest that they may serve as valuable molecule for the treatment of obesity related health complications. In adipose tissues, hydroxycinnamic acid derivatives inhibit macrophage infiltration and nuclear factor κB (NF-κB) activation in obese animals. Hydroxycinnamic acid derivatives also reduce the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and they increase the secretion of an anti-inflammatory agent adiponectin from adipocytes. Furthermore, hydroxycinnamic acid derivatives also prevent adipocyte differentiation and lower lipid profile in experimental animals. Through these diverse mechanisms hydroxycinnamic acid derivatives reduce obesity and curtail associated adverse health complications.

Objective-To compare the National Institute of Health's (NIH) body mass index (BMI)-based classification to identify obesity in comparison with the World Health Organization (WHO)'s percent body fat (%BF) -based reference standard among white, black and Hispanic reproductive-aged women.Methods-Body weight, height, BMI and %BF (DXA generated) were determined for 555 healthy adult women 20 to 33 years of age (M ± s.d.; 26.5 ± 4.0 years). Diagnostic accuracy of the NIH based obesity definition (BMI ≥ 30 kg/m 2 ) was determined using the WHO reference standard (%BF >35%).Results-Obesity as classified by the NIH (BMI ≥ 30 kg/m 2 ) and WHO (%BF >35%) identified 205 (36.9%) and 350 (63.1%) of the women as obese, respectively. NIH defined obesity cutoff values had 47.8%, 75.0% and 53.9% sensitivity in white, black and Hispanic women, respectively. White and Hispanic women had 2.9% greater %BF than black women for a given BMI. Receiver operating characteristics curves analyses showed that the respective sensitivities improved to 85.6%, 81.3%, and 83.2%, and that 311 women (56.0%) were classified as obese as a whole when race/ethnic specific BMI cutoff values driven by our data (BMI≥ 25.5, 28.7, and 26.2 kg/m 2 for white, black and Hispanic women, respectively) were used to detect %BF-defined obesity.Conclusions-Current BMI cutoff values recommended by the NIH failed to identify nearly half of reproductive-aged women who met the criteria for obesity by %BF. Using race/ethnic specific BMI cutoff values would more accurately identify obesity in this population than the existing classification system.

Purpose A 3-dose human papillomavirus (HPV) vaccine is recommended for adolescents to protect against HPV-related cervical and other cancers. The purpose of this study was to provide an update on HPV vaccine uptake among 11-17 year old girls residing in the US. Methods Data from the 2010 National Health Interview Survey (NHIS) were obtained to assess HPV vaccination status and its correlates. Multivariate logistic regression analyses were performed to examine HPV vaccine uptake of ≥1 dose and ≥3 doses among all girls, and completion of the 3-dose series among those who initiated (received ≥1 dose) the vaccine. Results Overall, 28.9% and 14.2% received ≥1 dose and ≥3 doses of vaccine: 14.5% and 3.0% among 11-12 year old girls, and 34.8% and 18.7% among 13-17 year olds, respectively. Hispanics had higher uptake of ≥1 dose (odds ratio (OR) 1.63, 95% confidence interval (CI) 1.22-2.17) than whites. Having received an influenza shot in the past year and parents’ awareness of the vaccine were significantly associated with receiving ≥1 dose (OR 1.88, 95% CI 1.51 -2.33 and OR 16.57, 95% CI 10.95 -25.06) and ≥3 doses (OR 1.48, 95% CI 1.13 -1.92 and OR 10.60, 95% CI 5.95 -18.88). A separate multivariate model based on girls who initiated the vaccine did not identify any significant correlates of 3-dose series completion. Among parents of unvaccinated girls, 60% were not interested in vaccinating their daughters and mentioned three main reasons: “does not need vaccine” (25.5%), “worried about safety” (19.3%) and “does not know enough about vaccine” (16.6%). Of those who were interested, 53.7% would pay $360-$500 for the vaccination, while 41.7% preferred to receive it at a much lower cost or free. Conclusions Only 1 out of 3 girls (11-17 years) have received ≥1 dose of HPV vaccine and much less have completed all 3 doses. Strategies should be taken to improve this vaccine uptake among girls, especially those 11-12 year olds, and to educate parents about the importance of vaccination.

No abstract