MD1 Deficiency Promotes Inflammatory Atrial Remodelling Induced by High-Fat Diets.

BACKGROUND: Myeloid differentiation protein 1 (MD1) is expressed in various tissues, including the heart. However, the role of MD1 in obesity-related atrial remodelling remains incompletely understood. Here, this study intends to determine the regulatory role and underlying mechanisms of MD1 in obesity-related atrial remodelling.

METHODS: A high-fat diet (HFD) feeding was performed in 6-week-old MD1-knockout (MD1-KO) mice and wild-type (WT) littermates for 20 weeks. Morphological, biochemical, functional, histological, and electrophysiological studies were conducted at the age of 26 weeks.

RESULTS: Our results revealed that the MD1 expression levels were downregulated in the atrium of the HFD-fed induced obesity mice. An increase in body weight, glucose intolerance, hyperlipidemia, and adverse atrial remodelling, such as atrial inflammation and fibrosis, were induced by HFD feeding in WT mice. Vulnerability to atrial fibrillation (AF) was also significantly increased by HFD feeding in WT mice. In addition, these adverse effects caused by HFD-fed induced obesity were further exaggerated in MD1-KO mice compared with WT mice. Mechanistically, MD1-KO activated TLR4/NF-κB signaling pathways, which led to atrial remodelling in mice fed by HFD by increasing the phosphorylation of p65 and IκBα.

CONCLUSIONS: Our data suggested that MD1 deficiency played an important role in accelerating the development of inflammatory atrial fibrosis and increasing vulnerability to AF in mice with HFD-fed induced obesity, providing an essential target for improving HFD-induced atrial remodelling.