Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes

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 reactive oxygen 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.

Lipoic acid inhibits leptin secretion and Sp1 activity in adipocytes

“…In the same way, other antioxidants such as Vitamin C and resveratrol also inhibit leptin secretion by adipocytes [56,57]. However, prooxidant agents (exposure to H 2 O 2 ) have also been shown to alter adipokine gene expression in adipocytes, including the inhibition of leptin secretion [58].…”

Vitamin C in the Treatment and/or Prevention of Obesity

“…Lower intracellular and extracellular ROS content following VC treatment in isolated adipocytes from lean rats (33) Mandarin juice (VC rich), jointly with low-calorie diet consumption, induced significant decrease in MDA and carbonyl group in plasma, and an increase in VC plasma levels, in children with severe obesity (69) Combined VE/VC supplementation induced lower hsCRP and cobalt-albumin binding in humans (70) An antioxidant supplementation (including VC) improved oxidative stress markers in obese children and adolescents (71) Lower lipid peroxidation (measured as F2-isoprostane levels) in humans after VE/VC supplementation. F2-isoprostane was strongly correlated with obesity (72) Improvement in impaired acetylcholine-stimulated vasodilatation in obese subjects following VC infusion (67) An antioxidant supplementation (VE, VC and carotene) prevented rise in oxidative stress induced by lower exercise in young overweight adults (73) Increase in plasma vitamin C levels correlated with decline in plasma free radicals and increase in GSH levels following chronic VC administration (63) Adipocyte differentiation and lipolysis VC treatment stimulated spontaneous 3T3-L1 mouse pre-adipocyte differentiation (74,76) Evidence Detail Reference…”

“…Lower GPDH gene expression and activity of mature adipocytes induced by VC treatment (30,33) Cellular growth stimulation of adipocytes by phosphate ascorbic acid treatment (74,75) Decreased lipolityc effect of cathecolamines and reduced basal lipolysis rate by VC treatment on adipose tissue from lean animals (28)…”

Effects of hyperoxia exposure on metabolic markers and gene expression in 3T3-L1 adipocytes

“…All the expression levels of the target genes studied were normalized by the expression of 18s as the selected internal control, as it demonstrated that no significant changes in its expression were detected after 95% O 2 exposition against control (data not shown). All procedures were performed according to a previous described protocol [16].…”

“…Indeed, several hypotheses have been proposed as the cause for the initiation of inflammatory processes during obesity, including oxidative stress [14,23], endoplasmic reticulum stress [21,24,38], and adipose tissue hypoxia [48,59]. Therapies trying to manage and counterbalance some of these adipose tissue pro-inflammatory conditions are under investigation [16,39,50]. Nevertheless, to our knowledge there are no studies trying to ameliorate the hypoxic state within adipose tissue.…”