# Western Diet-Induced Impairment of Left Atrium Cardiomyocyte Contractility in Female Wistar Rats Is Associated with Slowdown in the Cross-Bridge Cycle and Dephosphorylation of cMyBP-C

## TL;DR

A Western diet causes heart muscle dysfunction in female rats, particularly in the left atrium, by slowing muscle contractions and altering protein activity.

## Contribution

This study reveals diet-induced left atrium-specific contractile dysfunction linked to slowed cross-bridge cycling and cMyBP-C dephosphorylation in obese rats.

## Key findings

- Left atrium cardiomyocytes showed reduced contractility and slowed cross-bridge cycle with cMyBP-C dephosphorylation.
- Right atrium cardiomyocytes had molecular changes but no contractile dysfunction.
- Obesity from a Western diet caused early functional impairments without visible heart remodeling.

## Abstract

Obesity is a major risk factor for heart failure and atrial fibrillation. This study investigated the effects of diet-induced obesity on the molecular and cellular mechanisms of cardiomyocyte contractility in the left and right atria (LA and RA). Female Wistar rats were fed a Western diet (WD) for 18 weeks. Sarcomere dynamics and calcium transients were measured in unloaded cardiomyocytes. Actin–myosin interactions and contractile protein phosphorylation were assessed via an in vitro motility assay and phosphoprotein-specific gel electrophoresis. WD-fed rats developed obesity, hypertension, and metabolic alterations in the absence of echocardiographic or histological evidence of cardiac remodeling or systolic dysfunction. In LA cardiomyocytes, contractile dysfunction was indicated by increased calcium transient amplitude coupled with reduced shortening amplitude and relengthening velocity. This functional impairment correlated with a slowed myosin cross-bridge cycle and dephosphorylation of cMyBP-C. In contrast, RA cardiomyocytes displayed only molecular changes in response to obesity, including altered phosphorylation of most sarcomeric proteins and a decelerated cross-bridge cycle, but showed no evident contractile dysfunction. Thus, an 18-week WD reflects the early stages of contractile impairment, where functional deficits are specific to the LA, while RA alterations are confined to the molecular level.