Zinc-chelated Vitamin C Stimulates Adipogenesis of 3T3-L1 Cells

Abstract

Adipose tissue development and function play a critical role in the regulation of energy balance, lipid metabolism, and the pathophysiology of metabolic syndromes. Although the effect of zinc ascorbate supplementation in diabetes or glycemic control is known in humans, the underlying mechanism is not well described. Here, we investigated the effect of a zinc-chelated vitamin C (ZnC) compound on the adipogenic differentiation of 3T3-L1 preadipocytes. Treatment with ZnC for 8 d significantly promoted adipogenesis, which was characterized by increased glycerol-3-phosphate dehydrogenase activity and intracellular lipid accumulation in 3T3-L1 cells. Meanwhile, ZnC induced a pronounced up-regulation of the expression of glucose transporter type 4 (GLUT4) and the adipocyte-specific gene adipocyte protein 2 (aP2). Analysis of mRNA and protein levels further showed that ZnC increased the sequential expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), the key transcription factors of adipogenesis. These results indicate that ZnC could promote adipogenesis through PPARγ and C/EBPα, which act synergistically for the expression of aP2 and GLUT4, leading to the generation of insulin-responsive adipocytes and can thereby be useful as a novel therapeutic agent for the management of diabetes and related metabolic disorders.

Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism

“…A recent study demonstrated that zinc oxide (ZnO)-treatment (1–4 mg/l) upregulated PPARγ, FABP4, C/EBPα, and SREBP1 mRNA expression and stimulated lipid accumulation in adipocytes during adipogenesis [ 105 ]. Similar findings were obtained for zinc-chelated vitamin C [ 106 ]. In contrast, Justus et al [ 107 ] have shown that zinc deficiency does not exacerbate PPARγ gene expression in rats.…”

Chronic High Dose Zinc Supplementation Induces Visceral Adipose Tissue Hypertrophy without Altering Body Weight in Mice

“…Zinc is a stimulator for insulin signaling, which mimics several actions of insulin [ 31 ]. Ghosh et al reported that zinc-chelated vitamin C stimulated the adipogenesis in preadipocytes [ 14 ]. In addition, it is demonstrated in the current study that long-term chronic zinc supplementation induces adipose accumulation of the visceral adipose tissue in mice ( Figure 2 ).…”

“…Short-term zinc supplementation reduces blood glucose level in individuals with obesity and type 2 diabetes [ 10 , 11 , 12 ], as well as reverses alcohol-induced steatosis [ 13 ]. Moreover, it is also reported that zinc stimulates the adipose differentiation of preadipocytes in vitro [ 14 ]. Besides, Zhang et al reported that zinc supplementation induced intramuscular adipocytes content in weaned piglets [ 15 ].…”

Zinc transporter 7 deficiency affects lipid synthesis in adipocytes by inhibiting insulin‐dependent Akt activation and glucose uptake

“…On the other hand, zinc supplementation in obese subjects improves glucose tolerance and reduces risks of diabetes [12]. Zinc supplementation also promotes adipocyte differentiation in 3T3-L1 cells, whereas zinc deficiency inhibits it [13,14]. Furthermore, zinc has an insulin-like effect on adipogenesis in adipocytes [15].…”