Vitamin c inhibits leptin secretion and some glucose/lipid

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Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes
D F Garcia-Diaz, J Campion, F I Milagro, N Boque, M J Moreno-Aliaga and J A Martinez
Department of Nutrition and Food Sciences, Physiology and Toxicology, University of Navarra, c/Irunlarrea 1, 31008 Pamplona, Spain (Correspondence should be addressed to J A Martinez; Email:jalfmtz@unav.es)

Abstract
Antioxidant-based treatments are emerging as an interesting approach to possibly counteract obesity fat accumulation complications, since this is accompanied by an increased systemic oxidative stress. The aim of this study was to analyze specific metabolic effects of vitamin C (VC) on epididymal primary rat adipocytes. Cells were isolated and incubated for 72 h in culture medium,in the absence or presence of 1.6 nM insulin, within a range of VC concentrations (5–1000 mM). Glucose- and lipid-related variables as well as the secretion/expression patterns of several obesity-related genes were assessed. It was observed that VC dose dependently inhibited glucose uptake and lactate production, and also reduced glycerol release in both control and insulin-treated cells. Also,VC caused a dramatic concentration-dependent fall in leptin secretion especially in insulin-stimulated cells. In addition, VC (200 mM) induced Cdkn1a and Casp8, partially inhibited Irs3, and together with insulin drastically reduced Gpdh (listed as Gpd1 in the MGI database) gene expressions. Finally, VC and insulin down-regulatory effects were observed on extracellular and intracellular reactiveoxygen species production respectively. In summary, this experimental assay describes a specific effect of VC in isolated rat adipocytes on glucose and fat metabolism, and on the secretion/expression of important obesity-related proteins. Journal of Molecular Endocrinology (2010) 45, 33–43

Introduction
Worldwide, obesity is emerging as one of the major health threats (Powers et al. 2007). Indeed,it is well known that an excessive body fat accumulation, which defines this disease, could lead to several associated clinical manifestations such as type 2 diabetes, metabolic syndrome features, cardiovascular events, and arthritis (Bray 2004). These effects are related to a white adipose tissue (WAT) overgrowth and also to an impaired production and secretion of endogenous products by theenlarged adipocytes or the macrophages coexisting in the tissue (Bray 2004), which often have pro-inflammatory properties (Fantuzzi 2005). Actually, it has been reported that several inflammatory products derived from this tissue, such as TNF-a, IL6, MCP-1 (listed as CCL2 in the MGI database), and iNOS (NOS2), correlate with increased body adiposity (Ferrante 2007). In addition, it has been reported thatinflammatory-related pathways are activated in obesity and insulin resistance states (Yuan et al. 2001, Cai et al. 2005). Besides the secretion of these pro-inflammatory cytokines, the adipose tissue produces other substances that also have important local and systemic effects (Fantuzzi 2005). Among these molecules, leptin, which is related to the control of food intake and energy expenditure(Zhang et al. 1994), and adiponectin, which is related to significant insulin
Journal of Molecular Endocrinology (2010) 45, 33–43 0952–5041/10/045–033 q 2010 Society for Endocrinology Printed in Great Britain

sensitivity improvements (Kim et al. 2007), as well as visfatin, which has been reported to have controversial associations with insulin resistance and obesity, are metabolically relevant(Fukuhara et al. 2005, Haider et al. 2006, Varma et al. 2007). On the other hand, in obesity, a mitochondrial dysfunction and reactive oxygen species (ROS) overproduction as well as an association between oxidative stress and insulin resistance have been observed (Martinez 2006). In this sense, in obese patients (Vincent & Taylor 2006) and in overweight animal models (Furukawa et al. 2004, Milagro et...
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