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音量 1, 問題 1 (2012)

研究論文

Inflammatory Cytokines Link Obesity and Breast Cancer

Nalin Siriwardhana, Rett Layman, Ayub Karwandyar, Shiwani Patel, Blair Tage, Matthew Clark, Jessica Lampley, Courtney Rhody, Erica Smith, Arnold M Saxton, Naima Moustaid-Moussa and Jay Wimalasena

The risk of postmenopausal breast cancer is significantly increased by obesity. Further, low grade chronic inflammation, a hallmark of obesity, can contribute to detrimental health effects including high cancer incidence. Our goal is to understand the molecular basis for obesity-breast cancer interactions and dissect the role of inflammatory mediators secreted by adipocytes and breast cancer cells. Accordingly, we developed a three-dimensional (3D) coculture system to facilitate direct cell-cell interactions and also performed media transfer from adipocyte cultures to growing breast cell cultures. The co-culture system will facilitate both adipocyte and breast cell growth in an environment closely mimicking in-vivo tumor microenvironment. Co-cultures of human primary adipocytes obtained from lean and obese women with MCF10A, MCF7 and MDAMB231 breast cells (non-cancerous epithelial cells, cancerous and invasive breast cancer cells, respectively), led to cell type specific changes in secretion of several pro-inflammatory cytokines, such as IL-6 and TNFα, compared to monocultures. Regulation of cytokine secretion of breast cells by adipocytes and vice versa indicates the two-way communication between breast cells and adipocytes. Further, 3D co-culture and adipocyte conditioned media transfer experiments demonstrated that obese adipocytederived conditioned media can promote higher growth of breast cancer cells compared to that from lean adipocytes. Moreover, obese adipocyte conditioned media increased the activation of nuclear factor-κB (NF-κB) family members in breast cells, compared to lean adipocyte-derived media. Our results provide a novel model system to study adipocytebreast cancer cell interactions which may underlie the link between breast cancer and obesity and also demonstrate that inflammatory cytokines and other secreted factors are important in this interaction.

研究論文

Vitamin D and Metabolic Syndrome in Immigrant East Asian Women Living in Sydney, Australia: A Pilot

Kaye E Brock, Liang Ke, Fung Koo, Haeyoung Jang, Lindy Clemson, Elias Mpofu, Marilyn Tseng, David R Fraser, Markus J Seibel and Rebecca S Mason

Background: As epidemiological studies have linked vitamin D deficiency to risk of metabolic syndrome, we investigated vitamin D deficiency with metabolic syndrome prevalence in immigrant Asian women.
Materials and Methods: In a cross-sectional pilot survey of older East Asian women (n=85 aged 60-95) we examined the association between vitamin D status (measured by serum 25-hydroxyvitamin D) with
metabolicsyndrome risk factors.
Results: The population mean for 25-hydroxyvitamin D concentration in serum was 56 ± 22 nmol/L with forty percent being vitamin D deficient (< 50 nmol/L). Ninety-eight percent of the population had at least one metabolic syndrome risk factor, 85% had two, 55% had three and 8% had four. Having four metabolic syndrome risk factors was associated with a three fold risk of vitamin D deficiency. Vitamin D deficiency was associated with high non-fasting blood glucose levels ≥7.7 mmol/L (OR=5.2, 95%CI=1.8-18) and non-significantly, with being overweight (OR=1.8, 95%CI =0.7-5). In contrast, vitamin D deficiency was not associated with either hypertension or central obesity. Environmental factors associated with vitamin D deficiency in these data were no vitamin tablet intake (calcium or vitamin D) (OR=7.2, 95%CI=1.8-29; OR=6.3, 95%CI=1.2-32, respectively); not being acculturated to an Australian lifestyle, (OR=2.6, 95%CI=0.9-8) or less sun exposure on the weekends (OR=3.6, 95%CI=1.0-13). After adjustment for these predictors, if these Asian immigrants were vitamin D deficient they were at an eight fold risk of having high blood glucose measurements (OR=7.6, 95%CI=1-53).
Conclusion: Further larger prospective studies should be conducted to examine the association between vitamin D deficiency and risk of metabolic syndrome in similar immigrant populations.

研究論文

The Leptin to Adiponectin Ratio is a Marker of the Number of Metabolic Syndrome Criteria in French Adults

A Gauthier, S Dubois, S Bertrais, Y Gallois, C Aube, F Gagnadoux, P Cales, V Rohmer, G Leftheriotis, PH Ducluzeau

Aim: Visceral distribution of adipose tissue (AT) is one of the key components of Metabolic Syndrome (MetS). Plasma concentrations of leptin and adiponectin are closely linked to AT distribution. Pulse wave velocity (PWV), a marker of arterial stiffness, is linked to metabolic syndrome and cardiovascular risk. The purpose of this study is to describe the extent of the usefulness of the Leptin/Adiponectin (L/A) ratio as a marker of MetS.
Methods: Leptin and adiponectin concentrations, magnetic resonance image-based of visceral and subcutaneous fat measurements, and carotid PWV were analyzed in the subjects of a French prospective cohort composed of 97 subjects not presenting metabolic syndrome (MetS-), 122 patients with metabolic syndrome (MetS+) without diabetes, and 94 type 2 diabetics (T2D) with MetS.
Results: After adjustment for gender and age, leptinemia was found to be higher in MetS+ patients than in T2D patients. Adiponectinemia alone was not discriminated. There was a statistically significant difference in the L/A ratio between MetS- patients and the other groups. For the whole population, there is a positive correlation between the L/A and waist circumference, waist-to-hip ratio, visceral fat (r=0.53), triglyceride concentrations, fasting glucose concentrations, insulinemia, systolic and diastolic blood pressure, and number of MetS criteria (r=0.39). The L/A ratio is also significantly correlated with carotid artery stiffness.
Conclusion: This study demonstrates the potential usefulness of the L/A ratio as a marker, independent of age and gender, of a subject’s metabolic risk. The L/A Ratio is also a reliable marker for arterial stiffness.

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