High-fat diet induces systemic B-cell repertoire changes associated with insulin resistance

Area of Science:

• Immunology
• Metabolic Diseases
• Obesity Research

Background:

• Obesity-associated insulin resistance is linked to B-lymphocyte accumulation in visceral adipose tissue (VAT).
• B-cell depletion prevents the development of obesity-associated insulin resistance.

Purpose of the Study:

• To characterize the B-cell repertoires in mice exposed to high-fat diet (HFD) versus regular diet (RD).
• To identify potentially pathogenic B-cell populations involved in diet-induced metabolic changes.

Main Methods:

• High-throughput immunoglobulin (Ig) sequencing was performed on multiple tissues from mice on HFD and RD.
• Analysis focused on changes in Ig heavy-chain complementarity-determining region-3 (CDRH3) sequences and antibody properties.

Main Results:

• HFD significantly altered CDRH3 sequence biochemical properties, favoring shorter and more hydrophobic IgA antibodies across tissues.
• Convergent, highly similar antibody sequences were identified in the VAT of HFD mice but not RD mice.
• These convergent antibodies exhibited significant somatic mutation, indicating a specific immune response.

Conclusions:

• A high-fat diet profoundly impacts mouse B-cell repertoires, especially within adipose tissues.
• Dietary interventions can shape specific antibody responses, potentially influencing metabolic health and insulin resistance.