Sodium Butyrate Attenuates Diabetic Kidney Disease Partially via Histone Butyrylation Modification

Area of Science:

• Epigenetics
• Molecular Biology
• Nephrology

Background:

• Diabetic kidney disease (DKD) involves inflammation and fibrosis, influenced by epigenetic factors like histone posttranslational modifications (HPTMs).
• Butyrate, a short-chain fatty acid (SCFA), shows potential in preventing and treating DKD by reducing inflammation and fibrosis, but its molecular mechanisms are not fully understood.
• Histone lysine butyrylation (Kbu), a newly identified histone modification induced by butyrate, is implicated in regulating pathophysiological processes.

Purpose of the Study:

• To investigate the molecular mechanisms by which butyrate exerts its protective effects in DKD.
• To determine the role of histone lysine butyrylation (Kbu) in mediating the anti-inflammatory and anti-fibrotic actions of sodium butyrate (NaB) in DKD models.

Main Methods:

• DKD models (in vivo and in vitro) were treated with sodium butyrate (NaB).
• Histone Kbu and H3K9 butyrylation (H3K9bu) levels were assessed after NaB treatment.
• The effects of NaB were evaluated with and without the p300 inhibitor A485, which blocks histone Kbu.

Main Results:

• Sodium butyrate (NaB) treatment improved glucose and lipid metabolism, reduced proteinuria, and prevented renal failure in DKD models.
• NaB administration significantly induced histone Kbu and H3K9bu in both in vivo and in vitro DKD models.
• Inhibition of histone Kbu using A485 reversed the anti-inflammatory and anti-fibrosis effects of NaB, confirming Kbu's crucial role.

Conclusions:

• Sodium butyrate (NaB) effectively mitigates renal inflammation and fibrosis in DKD.
• The protective effects of NaB in DKD are mediated, at least in part, through the induction of histone lysine butyrylation (Kbu).
• Butyrate-induced histone Kbu, particularly H3K9bu, represents a significant molecular mechanism in DKD pathogenesis and a potential therapeutic target.