Gut microbiota control host lipid deposition through HDAC9-driven PPARγ acetylation

Area of Science:

• Metabolic diseases
• Gut microbiota
• Adipocyte biology

Background:

• Gut microbiota plays a crucial role in lipid metabolism and deposition.
• Dysbiosis is linked to metabolic disorders, but the underlying mechanisms are not fully understood.

Purpose of the Study:

• To investigate the role of gut microbiota in lipid absorption and deposition.
• To identify key molecular regulators in the gut microbiota-host interaction axis.
• To explore potential therapeutic targets for lipid-related metabolic diseases.

Main Methods:

• Utilized germ-free pigs and mice models.
• Performed human fecal microbiota transplantation.
• Integrated single-cell RNA sequencing of adipose tissue.
• Investigated the roles of HDAC9, PPARγ, and FABP4/5 in preadipocytes.

Main Results:

• Germ-free pigs and mice showed impaired lipid absorption and deposition, partially restored by microbiota transplantation.
• HDAC9 was identified as a key regulator in adipocytes, with high HDAC9 and low PPARγ expression in germ-free pigs.
• HDAC9 deficiency in preadipocytes enhanced FABP4/5-mediated lipid deposition by targeting PPARγ.
• Gut microbiota interaction with the host signaling cascade appears receptor-dependent (Dectin1, TLRs).

Conclusions:

• The gut microbiota-HDAC9-PPARγ axis is a critical regulator of adipocyte function and lipid deposition.
• This axis presents a potential therapeutic target for managing lipid-related metabolic diseases.
• Microbial receptor-dependent interactions mediate the influence of gut microbiota on host lipid metabolism.