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Metabolisches Syndrom und Inflammation

Metabolic syndrome and inflammation

Zusammenfassung

Adipositas geht mit einer als „Metaflammation“ bezeichneten chronisch-subklinischen Entzündung einher, die als unabhängiger Prädiktor für kardiovaskuläre Ereignisse, Diabetes mellitus Typ 2 und chronische Niereninsuffizienz (CKD) identifiziert wurde. Dabei kommt es auf Basis proinflammatorischer Signale, u. a. durch Adipozytenstress, zur Einwanderung von Immunzellen in das Fettgewebe. Zytotoxische T‑Zellen rekrutieren Makrophagen, die ihrerseits die Entzündung antreiben, sodass ein Circulus vitiosus aus sich verstärkenden Signalen mit einem proinflammatorischen Shift der Immunzellpopulation entsteht. Molekulare Endstrecke dessen ist eine zytokinvermittelte Insulinresistenz, die nicht nur den Grundstein für die Entwicklung eines metabolischen Syndroms legt, sondern die durch ihre sekundäre Hyperinsulinämie auch in der Niere Apoptose, Fibrose und endotheliale Dysfunktion triggert. Dieser Prozess wird durch entzündungsfördernde Mediatoren des Fettgewebes (Adipokine) zusätzlich gefördert. Einige immunsupprimierende Medikamente zeigen im Tierversuch erste positive Effekte auf adipositasassoziierte Folgeerkrankungen, sind bis dato aber für diese Indikation klinisch nicht etabliert.

Abstract

Obesity is accompanied by a chronic low-grade inflammation, called metaflammation, which has been identified as an independent predictor of cardiovascular events, type 2 diabetes mellitus and chronic kidney disease (CKD). Based on proinflammatory signals, primarily due to adipocyte stress, immune cells migrate into adipose tissue. Cytotoxic T cells recruit macrophages, which stimulate inflammation leading to a vicious circle of self-amplifying signals with a proinflammatory shift of immune cell populations. The molecular endpoint is a cytokine-mediated insulin resistance, which not only lays the foundation for developing metabolic syndrome but also triggers renal apoptosis, fibrosis and endothelial dysfunction due to secondary hyperinsulinemia. This process is further enhanced by inflammation-promoting mediators of adipose tissue called adipokines. Some immunosuppressive drugs showed initial beneficial effects on obesity-associated complications in animal models but are not yet clinically established for this indication.

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Correspondence to Sonja Rieckmann.

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S. Rieckmann, U. Stervbo und T.H. Westhoff geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Uwe Heemann, München

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Rieckmann, S., Stervbo, U. & Westhoff, T.H. Metabolisches Syndrom und Inflammation. Nephrologie 17, 304–309 (2022). https://doi.org/10.1007/s11560-022-00590-x

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Schlüsselwörter

  • Zytokinvermittelte Insulinresistenz
  • Immunsystem
  • Metaflammation
  • Niereninsuffizienz
  • Adipositas

Keywords

  • Cytokine-mediated insulin resistance
  • Immune system
  • Metaflammation
  • Kidney failure
  • Obesity