Abstract
Common variants of human fat mass- and obesity-associated gene Fto have been linked with higher body mass index, but the biological explanation for the link has remained obscure. Recent findings suggest that these variants affect the homeobox protein IRX3. Here we report that FTO has a role in white adipose tissue which modifies its response to high-fat feeding. Wild type and Fto-deficient mice were exposed to standard or high-fat diet for 16 weeks after which metabolism, behavior and white adipose tissue morphology were analyzed together with adipokine levels and relative expression of genes regulating white adipose tissue adipogenesis and Irx3. Our results indicate that Fto deficiency increases the expression of genes related to adipogenesis preventing adipocytes from becoming hypertrophic after high-fat diet. In addition, we report a novel finding of increased Irx3 expression in Fto-deficient mice after high-fat feeding indicating a complex link between FTO, IRX3 and fat metabolism.
Highlights
Common variants of human fat mass- and obesity-associated gene Fto have been linked with higher body mass index, but the biological explanation for the link has remained obscure
We investigated the effect of Fto depletion on genes related to adipogenesis, white adipose tissue (WAT) function as well as Irx[3] expression
While it is necessary to characterize the role of FTO in the normal physiological state, with a control diet (CD), it is important to characterize its function in response to the stimulation of WAT during consumption of a highfat diet (HFD)
Summary
Common variants of human fat mass- and obesity-associated gene Fto have been linked with higher body mass index, but the biological explanation for the link has remained obscure. The underlying molecular process linking the Fto gene with the regulation of adipocyte cell lineage will warrant further analysis, especially since a recent finding suggests a non-negligible role for brown adipose tissues in adult human metabolic response[9]. White fat remains the most abundant type of fat depot in humans and research focusing on the role of FTO in the metabolism of white adipocytes is required This can be achieved in mice by studying epididymal white adipose tissue (WAT) where the in vivo expression of Ucp[1] is absent under physiological conditions[10]. The white adipocyte acquires its functional characteristics allowing the storage of www.nature.com/scientificreports triglycerides and the control of energy balance via production of adipokines such as adiponectin and leptin These factors can play a role both in adipocyte differentiation and in the metabolic adaptation. The role of FTO in WAT biology and adipogenesis in vivo is investigated, together with how the dietary environment can provide new insights into the ways that FTO can control body weight regulation
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