Obesity is an epidemic condition linked to cardiovascular disease severity and mortality. Fat localization and type represent cardiovascular risk estimators. Importantly, visceral fat secretes adipokines known to promote low-grade inflammation that, in turn, modulate its secretome and cardiac metabolism. In this regard, IL-33 regulates the functions of various immune cells through ST2 binding and-following its role as an immune sensor to infection and stress-is involved in the pro-fibrotic remodeling of the myocardium. Here we further investigated the IL-33/ST2 effects on cardiac remodeling in obesity, focusing on molecular pathways linking adipose-derived IL-33 to the development of fibrosis or hypertrophy. We analyzed the Zucker Fatty rat model, and we developed in vitro models to mimic the adipose and myocardial relationship. We demonstrated a dysregulation of IL-33/ST2 signaling in both adipose and cardiac tissue, where they affected Epac proteins and myocardial gene expression, linked to pro-fibrotic signatures. In Zucker rats, pro-fibrotic effects were counteracted by ghrelin-induced IL-33 secretion, whose release influenced transcription factor expression and ST2 isoforms balance regulation. Finally, the effect of IL-33 signaling is dependent on several factors, such as cell types' origin and the balancing of ST2 isoforms. Noteworthy, it is reasonable to state that considering IL-33 to have a unique protective role should be considered over-simplistic.

• Klíčová slova
• 3/10 max, IL-33/ST2, adipose tissue, cardiac remodeling, cardiovascular disease, obesity,
• MeSH
• fibróza genetika   metabolismus   MeSH
• ghrelin genetika   metabolismus   MeSH
• interleukin 33 * genetika   metabolismus   MeSH
• interleukin-1 receptor-like 1 protein genetika   metabolismus   MeSH
• kardiomegalie genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   MeSH
• obezita * komplikace   genetika   metabolismus   MeSH
• potkani Zucker MeSH
• receptory interleukinu-1 * genetika   metabolismus   MeSH
• remodelace komor * genetika   fyziologie   MeSH
• výměnné faktory guaninnukleotidů genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ghrelin MeSH
• Il33 protein, rat MeSH Prohlížeč
• interleukin 33 * MeSH
• interleukin-1 receptor-like 1 protein MeSH
• obestatin, rat MeSH Prohlížeč
• Rapgef3 protein, rat MeSH Prohlížeč
• receptory interleukinu-1 * MeSH
• ST2 protein, rat MeSH Prohlížeč
• výměnné faktory guaninnukleotidů MeSH

Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first of three companion reviews that consider obesity. This review focuses on the genetics, viruses, insulin resistance, inflammation, gut microbiome, and circadian rhythms that promote obesity, along with hormones, growth factors, and organs and tissues that control its development. It shows that the regulation of energy balance (intake vs. expenditure) relies on the interplay of a variety of hormones from adipose tissue, gastrointestinal tract, pancreas, liver, and brain. It details how integrating central neurotransmitters and peripheral metabolic signals (e.g., leptin, insulin, ghrelin, peptide YY3-36) is essential for controlling energy homeostasis and feeding behavior. It describes the distinct types of adipocytes and how fat cell development is controlled by hormones and growth factors acting via a variety of receptors, including peroxisome proliferator-activated receptor-gamma, retinoid X, insulin, estrogen, androgen, glucocorticoid, thyroid hormone, liver X, constitutive androstane, pregnane X, farnesoid, and aryl hydrocarbon receptors. Finally, it demonstrates that obesity likely has origins in utero. Understanding these biochemical drivers of adiposity and metabolic dysfunction throughout the life cycle lends plausibility and credence to the "obesogen hypothesis" (i.e., the importance of environmental chemicals that disrupt these receptors to promote adiposity or alter metabolism), elucidated more fully in the two companion reviews.

• Klíčová slova
• Adipose tissue, Energy balance, Hormone receptors, Metabolism, Microbiome, Obesity,
• MeSH
• energetický metabolismus fyziologie   MeSH
• inzulin metabolismus   MeSH
• leptin * metabolismus   MeSH
• lidé MeSH
• obezita * metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• inzulin MeSH
• leptin * MeSH