Increased Fat Taste Preference in Progranulin-Deficient Mice

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.

C57bl/6 Mice Show Equivalent Taste Preferences toward Ruminant and Industrial Trans Fatty Acids

“…Similarly, a study showed ob / ob mice preferred a high-fat diet (HFD, carbohydrate 20 kcal%; protein 20 kcal%; fat 60 kcal%) when compared with control diet (carbohydrate 70 kcal%; protein 20 kcal%; fat 10 kcal%) [ 41 ]. Another study also demonstrated a preference for high fat intake in progranulin knockout mice (Grn−/−), where a preference for 2% milk over 0.3% milk was observed [ 24 ]. This increased consumption of energy resulted in 10% body weight gain, over a period of 7 days.…”

“…This increased consumption of energy resulted in 10% body weight gain, over a period of 7 days. Interestingly, control mice did not demonstrate preference toward fatter milk, and their body weight did not change [ 24 ]. Preference toward fat could be related to dopamine-related pathways [ 42 ].…”

“…Direct biochemical sensing of fat molecules in the oral cavity and the gastro-intestinal tract also appears to be involved in the taste inclination toward fat-containing foods [ 22 ]. All combined phenomena result in a higher preference for fat in mice [ 24 ].…”

The Implications of Taste and Olfaction in Nutrition and Health

“…Two studies on mammals underlined the role of genetic factors in the sensory perception of fats. Schumann et al [39] showed that a progranulin deficiency leads to a decreased expression of CD36 in the tongue, resulting in a greater preference for greasy tastes and fatty foods. When applied to humans, these data suggest that patients with diseases associated with low progranulin levels (for example, compulsive eating associated with frontotemporal dementia, psychiatric diseases, and comorbid obesity) may have a high preference for fatty tastes.…”