Inflamed adipose tissue: A culprit underlying obesity and heart failure with preserved ejection fraction

Abstract

The incidence of heart failure with preserved ejection fraction is increasing in patients with obesity, diabetes, hypertension, and in the aging population. However, there is a lack of adequate clinical treatment. Patients with obesity-related heart failure with preserved ejection fraction display unique pathophysiological and phenotypic characteristics, suggesting that obesity could be one of its specific phenotypes. There has been an increasing recognition that overnutrition in obesity causes adipose tissue expansion and local and systemic inflammation, which consequently exacerbates cardiac remodeling and leads to the development of obese heart failure with preserved ejection fraction. Furthermore, overnutrition leads to cellular metabolic reprogramming and activates inflammatory signaling cascades in various cardiac cells, thereby promoting maladaptive cardiac remodeling. Growing evidence indicates that the innate immune response pathway from the NLRP3 inflammasome, to interleukin-1 to interleukin-6, is involved in the generation of obesity-related systemic inflammation and heart failure with preserved ejection fraction. This review established the existence of obese heart failure with preserved ejection fraction based on structural and functional changes, elaborated the inflammation mechanisms of obese heart failure with preserved ejection fraction, proposed that NLRP3 inflammasome activation may play an important role in adiposity-induced inflammation, and summarized the potential therapeutic approaches.

Heart Failure with Preserved Ejection Fraction: The Pathophysiological Mechanisms behind the Clinical Phenotypes and the Therapeutic Approach

“…This has been associated with obese patients with more frequent structural remodeling, more pronounced diastolic dysfunction, and a higher risk of atrial fibrillation [94]. Chenyu Li et al linked obesity to inflammation as a possible mechanism for inducing cardiac senescence and HFpEF development [95]. They demonstrated the direct pro-inflammatory effects of nutrient overload.…”

Inflammation as a therapeutic target in heart failure with preserved ejection fraction

“…An alternative approach would be to use interventional strategies that might have multiple effects, of which an anti-inflammatory action is one. Such strategies include exercise and drugs inducing weight loss ( 150 ).…”

Obesity and metabolically healthy obesity: a review

“…It has been described that this condition could trigger a systemic inflammatory response through the production of proinflammatory cytokines 31 . Pre-adipocytes that reside in the stromal/vascular component of fatty tissue, secrete numerous proteins called adipokines, which are involved in the autocrine and paracrine regulation of various processes, including body weight, the immune system, and vascular and reproductive functions 31,32 .…”

“…In the presence of hypertrophy and hyperplasia of adipocytes and pre-adipocytes, the migration of monocytes in the form of macrophages from the intravascular space to the extravascular space increases. This contributes to the synthesis and release of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, interleukin-1 beta, interleukin-8, hepatocyte growth factor, apolipoprotein A3, and macrophage migration inhibitory factor, as well as inflammatory modulators such as leptin, adiponectin, and resistin 32 .…”