Postbiotics lower adipose tissue MHCII inflammation and blood glucose in obese mice, dependent on sex.

Obesity is characterized by compartmentalized inflammation in metabolic tissues and risk of dysglycemia, which can be influenced by bacterial components and metabolites (i.e., postbiotics). The postbiotic muramyl dipeptide (MDP) improves blood glucose control in obese male, but not female, mice. The immune response linking MDP to blood glucose was not known. We hypothesized that MDP lowers class II major histocompatibility complex (MHCII) immunity in a sex- and tissue-dependent manner, and that lower MHCII immunity in adipose tissue correlates with improved blood glucose control in obese male mice. We showed that diet-induced obesity increased the transcript levels of multiple components of MHCII immunity in adipose tissue of obese male and female mice, which positively correlated with increased fasting blood glucose. We found that 5 weeks of MDP injections lowered transcript levels of MHCII surface expression and T-cell activation markers in adipose tissue of obese male mice, with minimal changes in the liver or in obese female mice. Lower MHCII inflammatory markers in adipose tissue positively correlated with improved glucose tolerance, but not fasting blood glucose, in obese male mice. Therefore, postbiotic-induced sex-specific improvements blood glucose control are linked to lower transcription of MHCII inflammation in adipose tissue of obese male mice.