The association of carbohydrate intake with cardiovascular diseases (CVD) has been overshadowed by the premise that dietary fats are the main factor associated with early cardiovascular death [1]. More recently, large population studies implicate sugar as playing a major role in cardiovascular deaths and put high-refined sugar at the top of the discussion about reducing consumption of processed foods [2], [3], [4]. It was highlighted that high-refined carbohydrate intake, but not dietary fats, was progressively associated with the relative cardiovascular risk of death [2], [4]. Nonetheless, the consumption of ultra-processed foods has exponentially increased in the last decades [1], [5]. Processed foods are enriched with refined carbohydrates, which makes them the main dietary source of this type of sugar [6].

Highly refined carbohydrates, those with reduced fiber and a high-glycemic load, are extensively used as added sugar in ultra-processed foods, such as sweetened beverages, and confectionery. It is a fundamental definition, once refined sugar, not starch, is the carbohydrate component associated with increased cardiovascular risk independently of obesity [3], [7]. Even CVDs remaining the leading cause of death worldwide [8], the relation between refined carbohydrate intake and CVD has been underestimated due to few and nonuniform reports demonstrating added sugar consumption profiles from most countries [9].

Despite the metabolic disturbances, several reports show that animals fed for a long time with high fructose or sucrose diets develop cardiac dysfunction [10], [11], which may account for the higher cardiovascular mortality found in clinical studies. Carbohydrate restriction, on the other side, contributed to reduced levels of high sensitivity C-reactive protein in a clinical trial [12]. However, the inflammatory mechanisms involved in sugar-induced cardiac damage have not been investigated so far.

It is extensively accepted that inflammation takes part in the pathophysiology of heart failure of several etiologies, such as ischemic injury, myocarditis, hypertensive heart disease [13], [14], and recently, cardiac damage of patients with COVID-19 [15]. In these diseases, infiltrating leukocytes and local production of cytokines worse cardiac contractility and induce apoptosis, remodeling, and arrhythmias. Pro-inflammatory and pro-fibrotic cytokines (such as TNF-α, TGF-β, IL-1β, IL-6, and others) and chemokines (mainly CCL-2) promote a pro-oxidative environment, leading to cardiac remodeling and dysfunction [16], [17]. The anti-inflammatory cytokine IL-10, on the other side, regulates oxidative stress and fibrosis, improving cardiac function and preventing pathological remodeling [18], [19].

Inflammation is also involved in cardiac damage induced by long-term hypercaloric diets, such as high-fat and cafeteria diets [19], [20]. Short-term consumption of an isocaloric high-refined carbohydrate diet (HC diet) induces adipose tissue growth and inflammation in mice [21]. However, cardiac alterations triggered by the HC diet are still poorly understood and no correlation with local inflammatory markers has been made. Our hypothesis is that refined sugar consumption can cause heart inflammation accompanied of early structural and contractile disturbances. The purpose of this work was to determine HC diet-induced cardiac morphological and functional changes. Accordingly, the cardiac levels of cytokines, chemokines, and profibrotic factors over 2, 4, and 8-week periods in response to high-refined carbohydrate feeding in mice were also addressed.