Abstract
Progranulin deficiency in mice is associated with deregulations of the scavenger receptor signaling of CD36/SCARB3 in immune disease models, and CD36 is a dominant receptor in taste bud cells in the tongue and contributes to the sensation of dietary fats. Progranulin-deficient mice (Grn−/−) are moderately overweight during middle age. We therefore asked if there was a connection between progranulin/CD36 in the tongue and fat taste preferences. By using unbiased behavioral analyses in IntelliCages and Phenomaster cages we showed that progranulin-deficient mice (Grn−/−) developed a strong preference of fat taste in the form of 2% milk over 0.3% milk, and for diluted MCTs versus tap water. The fat preference in the 7d-IntelliCage observation period caused an increase of 10% in the body weight of Grn−/− mice, which did not occur in the wildtype controls. CD36 expression in taste buds was reduced in Grn−/− mice at RNA and histology levels. There were no differences in the plasma or tongue lipids of various classes including sphingolipids, ceramides and endocannabinoids. The data suggest that progranulin deficiency leads to a lower expression of CD36 in the tongue resulting in a stronger urge for fatty taste and fatty nutrition.
Highlights
Progranulin is a multifaceted, neurotrophic and anti-inflammatory protein, which is essential for neuronal survival and regeneration after axonal damage [1,2]
Fat taste is supposed to be mediated through cluster of differentiation 36 (CD36), which is highly expressed in gustatory cells of taste buds, in circumvallate papillae, and we have previously shown that progranulin regulates CD36 expression in immune cells [10]
We showed that progranulin deficiency urged mice to take up fat nutrients due to the association with low levels of CD36 in taste buds, likely increasing the urge for fatty foods
Summary
Progranulin is a multifaceted, neurotrophic and anti-inflammatory protein, which is essential for neuronal survival and regeneration after axonal damage [1,2]. Loss of progranulin in mice leads to synaptic pruning by activated microglia [3]. Progranulin reduces inflammation [7,8] by increasing the phagocytosis activity of myeloid immune cells [9,10] and possibly via anti-TNF signalling [11,12]. Progranulin promotes the antigen-stimulated activation of T-cells in the context of autoimmunity [10,13,14]. Progranulin promotes insulin resistance in experimental models [17,22,23,24]. Its loss rather than progranulin overexpression was associated with unfavourable metabolic features in mice such as body weight gain, low voluntary exercise [25], increased atherosclerosis and cholesterol accumulation in macrophages [26]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
