Branched-chain amino acids (BCAA) are essential amino acids utilized in anabolic and catabolic metabolism. While extensively studied in obesity and diabetes, recent evidence suggests an important role for BCAA metabolism in cancer. Elevated plasma levels of BCAA are associated with an increased risk of developing pancreatic cancer, namely pancreatic ductal adenocarcinoma (PDAC), a tumor with one of the highest 1-year mortality rates. The dreadful prognosis for PDAC patients could be attributable also to the early and frequent development of cancer cachexia, a fatal host metabolic reprogramming leading to muscle and adipose wasting. We propose that BCAA dysmetabolism is a unifying component of several pathological conditions, i.e., obesity, insulin resistance, and PDAC. These conditions are mutually dependent since PDAC ranks among cancers tightly associated with obesity and insulin resistance. It is also well-established that PDAC itself can trigger insulin resistance and new-onset diabetes. However, the exact link between BCAA metabolism, development of PDAC, and tissue wasting is still unclear. Although tissue-specific intracellular and systemic metabolism of BCAA is being intensively studied, unresolved questions related to PDAC and cancer cachexia remain, namely, whether elevated circulating BCAA contribute to PDAC etiology, what is the biological background of BCAA elevation, and what is the role of adipose tissue relative to BCAA metabolism during cancer cachexia. To cover those issues, we provide our view on BCAA metabolism at the intracellular, tissue, and whole-body level, with special emphasis on different metabolic links to BCAA intermediates and the role of insulin in substrate handling.

• Klíčová slova
• Adipose tissue, BCAA metabolism, Cancer cachexia, Insulin resistance, PDAC,
• MeSH
• diabetes mellitus * MeSH
• duktální karcinom slinivky břišní * etiologie   patologie   MeSH
• inzulinová rezistence * MeSH
• kachexie etiologie   MeSH
• lidé MeSH
• nádory slinivky břišní * patologie   MeSH
• obezita komplikace   metabolismus   MeSH
• větvené aminokyseliny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• větvené aminokyseliny MeSH

Osteopontin (OPN) is a multifaceted matricellular protein, with well-recognized roles in both the physiological and pathological processes in the body. OPN is expressed in the main organs and cell types, in which it induces different biological actions. During physiological conditioning, OPN acts as both an intracellular protein and soluble excreted cytokine, regulating tissue remodeling and immune-infiltrate in adipose tissue the heart and the kidney. In contrast, the increased expression of OPN has been correlated with the severity of the cardiovascular and renal outcomes associated with obesity. Indeed, OPN expression is at the "cross roads" of visceral fat extension, cardiovascular diseases (CVDs) and renal disorders, in which OPN orchestrates the molecular interactions, leading to chronic low-grade inflammation. The common factor associated with OPN overexpression in adipose, cardiac and renal tissues seems attributable to the concomitant increase in visceral fat size and the increase in infiltrated OPN+ macrophages. This review underlines the current knowledge on the molecular interactions between obesity and the cardiac-renal disorders ruled by OPN.

• Klíčová slova
• cardiovascular diseases (CVDs), chronic kidney disease (CKD), obesity, osteopontin (OPN), renal disorders, visceral adipose tissue (VAT),
• MeSH
• inzulinová rezistence genetika   MeSH
• ledviny metabolismus   patologie   MeSH
• lidé MeSH
• myokard metabolismus   patologie   MeSH
• nemoci ledvin genetika   metabolismus   patologie   MeSH
• nemoci srdce genetika   metabolismus   patologie   MeSH
• nitrobřišní tuk metabolismus   MeSH
• obezita genetika   metabolismus   patologie   MeSH
• osteopontin genetika   metabolismus   MeSH
• tuková tkáň metabolismus   MeSH
• zánět genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• osteopontin MeSH