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Adipositas und Krebs

Obesity and cancer

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Zusammenfassung

Die Inzidenz von Adipositas ist in den vergangenen Jahrzehnten in der westlichen Welt dramatisch angestiegen. Epidemiologische Daten zeigen, dass Fettleibigkeit mit einem erhöhten Risiko assoziiert ist, an bestimmten (aber nicht allen) Krebsarten zu erkranken, wobei das Krebsspektrum geschlechtsspezifische Unterschiede aufweist. Die zugrundeliegenden Mechanismen und potentiellen Faktoren sind noch weitgehend ungeklärt. Dieser Beitrag gibt einen Überblick über den gegenwärtigen Stand der Forschung. Es wird angenommen, dass Insulinresistenz und eine chronische, subklinische Entzündung im viszeralen Fettgewebe wichtige metabolische Prozesse darstellen. Als Folge davon kommt es zu Veränderungen in den Serumspiegeln von Insulin, Glukose, freien Fettsäuren, IGF-1/-2 und einer Freisetzung von proinflammatorischen Zytokinen und anderen biologisch aktiven Molekülen aus dem Fettgewebe, wie Adipokinen (z. B. Leptine und Adiponektin), VEGF und Geschlechtshormonen. Alle diese Faktoren wie auch Mikrobiota des Darms und sekundäre Gallensäuren können direkt oder indirekt das „tumor microenvironment“ so verändern, dass über Stimulation von Antiapoptose, Zellproliferation, Angiogenese und Invasion/Metastasierung der Krebszellen die Tumorprogression gefördert wird. Therapeutische Strategien sind auf eine Beseitigung der Entzündung und auf eine Wiederherstellung eines funktionalen Fettgewebes ausgerichtet. Während die bariatrische Chirurgie einen therapeutischen Nutzen in Hinblick auf die Krebsinzidenz zu bringen scheint, müssen andere Interventionen, wie die Umwandlung von Fettgewebsmakrophagen zu einem antiinflammatorischen M2-Phänotyp oder die pharmakologische Modulation der Adipokin-Serumspiegel, noch experimentell und klinisch auf ihre Eignung in Bezug auf Therapie und Prävention adipositasassoziierter Krebserkrankungen evaluiert werden.

Abstract

The incidence of obesity in the western world has increased dramatically during recent decades. Epidemiological data suggest that obesity is associated with an increased risk of several but not all types of cancers, with clear sex-specific differences. The underlying mechanisms are still a matter of debate. This review focuses on the potential factors linking obesity to cancer. Current experimental evidence suggests that insulin resistance and a chronic, subclinical inflammation in the visceral fat are the major metabolic events causing alterations in the levels of insulin, glucose, free fatty acids, insulin-like growth factor 1 (IGF-1) and 2, adipose tissue-derived proinflammatory cytokines and other bioactive molecules, such as adipokines (e.g. leptin and adiponectin), vascular endothelial growth factor (VEGF), sex hormones, gut microbiota and secondary bile acids. All these factors may act directly or indirectly on the tumor microenvironment to drive tumor progression via stimulation of cell survival/antiapoptosis, cell proliferation, angiogenesis and invasion/metastasis of the cancer cells. Therapeutic strategies that target dysfunctional or inflamed fat and have been shown to benefit patients include bariatric surgery, while other cell or hormone-directed interventions, such as conversion of visceral fat macrophages to an anti-inflammatory M2 phenotype or the pharmacological modulation of serum adipokine levels are still theoretical and need to be clinically evaluated for their ability to successfully treat or prevent obesity-related cancers.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. H. Ungefroren, F. Gieseler und H. Lehnert geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Abteilung Hämatologie/Onkologie, Medizinische Klinik I -ZK,UKSH Campus Lübeck, Universitätsklinikum Schleswig-Holstein, Ratzeburger Allee 160, 23538, Lübeck, Deutschland

    H. Ungefroren, F. Gieseler & H. Lehnert

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  1. H. Ungefroren
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  2. F. Gieseler
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  3. H. Lehnert
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Correspondence to H. Ungefroren.

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Ungefroren, H., Gieseler, F. & Lehnert, H. Adipositas und Krebs. Internist 56, 127–136 (2015). https://doi.org/10.1007/s00108-014-3536-4

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