Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/19/2012
Publication Date: 4/11/2012
Citation: Park, J.B., Wang, T.T. 2012. Safflomide increases the expression of adiponectin in vitro and in vivo: Implication for hypoadiponectemia, visceral obesity, and insulin resistance. Journal of Agricultural and Food Chemistry. 25(60):4048-52.
Interpretive Summary: Obesity is a serious social, financial, and health problem that is often closely associated with the rising incidence of subclinical inflammation, dyslipidemia, diabetes, cardiovascular diseases, hypertension, and other related diseases. Adiponectin is an adipocyte-derived adipokine with anti-diabetic, anti-atherogenic, and anti-inflammatory functions. When people become obese the expression of adiponectin is significantly decreased and frequently followed by increasing insulin-resistance, which is a feature of the metabolic syndrome that is strongly associated with many chronic diseases. In this study, safflomide and analogues found in plants were able to up-regulate the expression of adiponectin in hypertrophic 3T3-L1 cells in culture and in rats fed a high-fat and high-fructose diet. Furthermore, the rats supplemented with safflomide showed an apparent reduction in bodyweight and visceral fat, and improved insulin resistance. These data suggested that safflomide is a very potent plant-derived amide able to increase adiponectin production in 3T3-L1 cells and the plasma of rats fed safflomide. The outcomes of this study will provide researchers in nutrition, molecular biology, and related medicinal fields with new information about the potential effects of safflomide found in plants.
Technical Abstract: Safflomide (N-caffeoyltryptamine) is a phenolic amide with serotonin-receptor antagonist and anti-oxidant activities. We investigated the effects of safflomide on the expression of adipokines in vitro and in vivo. Safflomide did not affect the expressions of TNF-a, IL-6, and MCP-1/CCL2 in hypertrophic 3T3-L1 cells, but up-regulated adiponectin mRNA 5 to 45 fold at concentrations between 1 and 20 µM (P < 0.05). Because safflomide is a non-selective 5-HT receptor antagonist and because the expression of 5-HT2A receptor is often inversely correlated to adiponectin expression, the potential effects of 5-HT receptor antagonist activity of safflomide on the expression of adiponectin was further investigated in 3T3-L1 cells. At the concentration of 10 µM, safflomide was able to increase adiponectin protein production in 3T3-L1 cells more than 4 fold (P < 0.05), which was greater than the 5-HT2A antagonist ketanserin. The up-regulation was partially suppressed by treatment with 5-HT2A agonists (serotonin and a-Me-5-HT), suggesting that safflomide may up-regulate adiponectin expression more than block 5-HT2A receptors. Up-regulation was likely attributed to the antioxidant activity of safflomide because two safflomide analogues (N-cinnamoyltryptamine and N-coumaroyltryptamine) with less antioxidant activity were not as potent as safflomide. Rats supplemented with safflomide in the diet showed a significant plasma adiponectin increase with a significant reduction in body weight, visceral fat, and improved insulin resistance compared to non-supplemented rats, demonstrating the in vivo activity of safflomide. These data suggested that safflomide may have beneficial effects on obesity-related conditions such as low adiponectin, visceral obesity, and insulin resistance.