Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters

Abstract

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. In HFD-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.

Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake

“…A key beneficial role of the human gut microbiota is producing the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, which are metabolic end products of anaerobic fermentation [1,2]. These SCFA, most notably among them, butyrate, have been shown to promote gastrointestinal (GI) barrier integrity, lower inflammation, increase resistance to pathogen invasion, and contribute positively to enteroendocrine signaling and energy homeostasis [3][4][5][6][7][8][9]. Augmenting these functions may explain the protective role of SCFAs in diseases ranging from obesity to inflammatory bowel diseases [3,[10][11][12][13][14][15][16][17][18][19][20].…”

Bioassay-guided isolation of active anti-adipogenic compound from royal jelly and the study of possible mechanisms

“…Western blotting was performed as described by Lee et al, 2017 [23]. Cell lysates were harvested in the different time frame during the differentiation period for western blot analysis of various proteins.…”