# Research on the mechanism of cow milk protein dietary intervention in ameliorating systemic chronic inflammation in type 2 diabetes by disrupting the ROS-M1 macrophage axis

## TL;DR

This study shows how cow milk protein reduces chronic inflammation in type 2 diabetes by disrupting harmful immune processes.

## Contribution

The paper reveals a novel mechanism by which cow milk protein disrupts the ROS-M1 macrophage axis in type 2 diabetes.

## Key findings

- Cow milk protein reduces fasting blood glucose and body weight loss in diabetic mice.
- CMP lowers oxidative stress and suppresses M1 macrophage polarization and pro-inflammatory cytokines.
- CMP improves liver, intestine, and kidney pathologies in type 2 diabetes.

## Abstract

Recent studies suggest that type 2 diabetes mellitus (T2DM) is characterized by a systemic, low-grade chronic inflammatory state. Although cow milk protein (CMP) has been shown to alleviate this inflammation, its underlying mechanisms remain unclear.

Therefore, we investigated how CMP mitigates systemic chronic inflammation in T2DM using both in vitro digestion and mouse models.

The in vitro digestion model demonstrated that CMP, with its low degree of hydrolysis, exhibits significant anti-α-amylase and antioxidant activities. In the in vivo study, CMP markedly reduced fasting blood glucose (FBG) and reversed diabetes-related body weight loss. CMP intervention significantly decreased oxidative stress markers, including malondialdehyde (MDA) and reactive oxygen species (ROS), while enhancing the activity of the antioxidant enzyme glutathione peroxidase (GSH-Px). Moreover, CMP suppressed macrophage polarization toward the M1 phenotype and reduced the levels of pro-inflammatory cytokines. Finally, CMP administration ameliorated lipid infiltration in the liver and intestine, mitigated pancreatic islet atrophy, and concurrently alleviated renal pathologies such as glomerular hypertrophy, glycation, and fibrosis.

In conclusion, CMP ameliorates systemic chronic inflammation in T2DM by disrupting the ROS–M1 macrophage vicious cycle.

Diagram illustrating the impact of high glucose and cow milk protein on Th17 cells and systemic inflammation. High glucose activates Th17 cells, producing reactive oxygen species (ROS) and promoting M1 macrophage activation, increasing IL-2, IL-6, and TNF-alpha, leading to a systemic inflammatory response. Cow milk protein, however, encourages M2 macrophage activation, reducing IL-2 and IL-6 while increasing IL-10, resulting in improved systemic inflammation.