The Dialogue Around Risky GUCY1B3-Procedures

, 2003?and?Xu et?al., 2003), and we assessed whether the increased expression of caspase-1 in adipose tissue was due to an increase in the infiltrating macrophages or the adipocytes themselves. Partial depletion of macrophages from adipose tissue of animals fed a HFD decreased GUCY1B3 the expression of the macrophage marker CD68, yet did not alter the expression of caspase-1 (Figure?2H), suggesting that caspase-1 effects on adipose tissue are not only exerted through infiltrating macrophages. Together, these data show that both diet-induced and genetically induced obesity result in activation of caspase-1 and increased levels of IL-1�� and IL-18 in adipose tissue. To assess in more detail the role of caspase-1 in adipocyte function, preadipocytes from caspase-1-deficient mice and wild-type mice were differentiated toward adipocytes using a standard adipocyte differentiation protocol. In the absence of caspase-1, adipogenesis was enhanced, as illustrated by oil red O staining (Figure?3A) and increased gene expression levels of GLUT-4, adiponectin, and PPAR�� (Figure?3B). Importantly, secretion of adiponectin, a key regulator of insulin sensitivity (Kadowaki et?al., 2006), was significantly elevated in caspase-1-deficient adipocytes (Figure?3C). Additionally, insulin signaling in caspase-1-deficient adipocytes was ameliorated, as visualized by an increased phosphorylation of Akt (Figure?3D) (relative pAKT/AKT ratio, WT 10?nm PD173074 in vivo insulin versus caspase-1?/? 10?nm insulin, Ulixertinib 1 �� 0.53 versus 3.09 �� 0.12, p value?