title: Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence.
abstract: Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γsecretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM) in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity.
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Ina
authors.identifier: 0000-0002-6075-5435
authors.initials: I
authors.lastname: Bähr
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goritz
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Henriette
authors.initials: H
authors.lastname: Doberstein
authors.affiliation: Institute of Pathology, University Hospital of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Grit Gesine Ruth
authors.initials: GG
authors.lastname: Hiller
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstock
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Jahn
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Ole
authors.initials: O
authors.lastname: Pörtner
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Berreis
authors.affiliation: Clinic for Internal Medicine IV, Department of Hematology and Oncology, University Hospital of Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Spielmann
authors.affiliation: Institute of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Heike
authors.identifier: 0000-0001-8866-3543
authors.initials: H
authors.lastname: Kielstein