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Korean J Physiol Pharmacol 2017 Sep; 21(5): 519-529
Eun-Sol Lee1,#, Dong-Sung Lee2,#, Prakash Raj Pandeya1, Youn-Chul Kim1, Dae-Gil Kang3,4, Ho-Sub Lee3,4, Byung-Chul Oh5,6, and Dae Ho Lee7,8,*
Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters
1College of Pharmacy, Wonkwang University, Iksan 54538, 2College of Pharmacy, Chosun University, Gwangju 61452, 3Hanbang Body Fluid Research Center,Wonkwang University, Iksan 54538, 4College of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 54538,5Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon 21999, 6Department of physiology, College of Medicine, GachonUniversity, Incheon 21999, 7Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21565, 8Department of Internal Medicine, Gachon University College of Medicine, Incheon 21999, Korea
Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of 1,000 µM. InHFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and IL-1β, and DPP-4 activity, and suppressed the increase in body weight. On the contrary,various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of TNF-α, IL-6, and IL-1β. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.
Keyword : Dipeptidyl peptidase 4, HepG2 cells, Mesangial cells, Obesity, Sodium butyrate