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Etude du rôle des sous-populations monocytaires dans l'obésité et l'insulinorésistance

Abstract : Obesity is associated with low grade inflammation. Blood monocytes, key players in innate immunity, are expanded during obesity. In mice, monocytes are divided in two main subsets, the Gr1high and the Gr1low monocytes. These two subsets have different functions, but their role in the physiopathology of obesity is still unknown. Here we show that High Fat Diet (HFD) induces a monocytosis in mice that is mainly due to Gr1low monocytes expansion. Moreover, HFD induces a strong up-regulation of CD11c specifically on this cell subset. Using different mice models which differ in Gr1low monocytes number, we found a strinking correlation between the proportion of Gr1low monocytes and the body weight or with the insulin resistance statue. Indeed, CX3CR1 deficient mice, which have a reduced proportion of Gr1low monocytes upon HFD, were more insulin resistant and have a lower body weight than control mice. Conversely, mice expressing the anti-apoptotic gene hBcl2 under the CD11c promoter control, which have an increased Gr1low monocytes population, have higher insulin sensitivity upon HFD. Furthermore, in CD11chBcl2/CX3CR1 KI mice, a partial rescue of Gr1low monocytes was associated with a total rescue of body weight. Our data also strongly suggest that, in CX3CR1 KI mice, an increased adipose tissue inflammation due to a defect of M2 macrophages functions is responsible for the metabolic alterations. Our data strongly suggest that Gr1low monocytes i) play a new key protective role against obesity induced insulin-resistance and ii) promotes body weight gain in mice fed a HFD. Indeed, this monocyte subset likely promotes M2 macrophage functions in adipose tissue, decreasing its inflammation and thus favoring its development and insulin sensitivity.
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  • HAL Id : tel-00824652, version 1

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Sophie Béliard-Lasserre. Etude du rôle des sous-populations monocytaires dans l'obésité et l'insulinorésistance. Physiologie [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2011. Français. ⟨NNT : 2011PA066445⟩. ⟨tel-00824652⟩

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