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. 2018;7(4):277-284.
doi: 10.1080/21623945.2018.1516098. Epub 2018 Oct 11.

SGLT6 - A pharmacological target for the treatment of obesity?

Tamara Baader-Pagler  1 , Matthias Eckhardt  2 , Frank Himmelsbach  2 , Achim Sauer  3 , Birgit E Stierstorfer  3 , Bradford S Hamilton  1
Affiliations

SGLT6 - A pharmacological target for the treatment of obesity?

Tamara Baader-Pagler et al. Adipocyte. 2018.

Abstract

Despite increased knowledge of nutrient intake regulation and energy homeostasis, treatment options for obesity remain limited. Food reward consists of two branches: gustatory and post-ingestive nutritive information. Drosophila lacking dSLC5A11 (sodium/glucose cotransporter 6-SGLT6) prefer L-glucose over D-glucose independently of their state of satiety. Human SGLT6 is an active transporter of myo-inositol and D-glucose. We investigated expression of SGLT6 in human tissue and found a significant expression in the small intestine and brain. The preference between a metabolizable and a non-metabolizable sugar was tested in 3 mouse models with a selective and potent SGLT6 inhibitor. No influence on sugar preference was seen with SGLT6 inhibition. These studies suggest that SGLT6 does not play a significant role in nutrient sensing in mammals.

Keywords: SGLT6; hunger; obesity; reward; sugar.

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Figures

Figure 1.
Figure 1.
SGLT6 immunohistochemistry. Strong cytoplasmic SGLT6 staining is present in neuronal cells of mouse (a), rat (b) and human (c) cortical brain areas and includes the neuronal processes, also. Similar staining pattern is shown by the cerebellar purkinje cells (d-f). In the small intestine (g-i), SGLT6 is found intracytoplasmic in epithelial cells of the villi, cells of the lamina propria and myenteric ganglion cells. Isotype controls of the respective tissues are negative (Supplementary Figure 1). SGLT6 staining is indicated in brown (DAB), nuclei are counterstained in blue with Hematoxylin.
Figure 2.
Figure 2.
Effect of an SGLT6 inhibitor on sucrose vs. sucralose preference. Single housed mice (n = 8/group) treated either with Cpd B (30 mg/kg, BID) or vehicle received a choice between 175 mM sucrose and 1.5 mM sucralose for 2 consecutive days. Preference was assessed using a lickometer system recording licks per mouse. Data is presented as percent of total licks of 2 d for sucrose or sucralose (a) or absolute licks per hour for vehicle (b) or Cpd B (c). Data is given as Mean ± SEM (a) or as Mean (b, c). Data (a) were compared by 2-way ANOVA followed by Bonferroni multiple comparison test.
Figure 3.
Figure 3.
Effect of an SGLT6 inhibitor on preference shift between sucrose vs. sucralose/saccharine. Single housed mice (n = 8/group) treated either with Cpd B (30 mg/kg, BID) or vehicle received a choice between a mix of 0.1% sucralose/0.1% saccharine and 8% sucrose for 7 consecutive days. Preference was assessed using a lickometer system recording licks per mouse. Data is presented as percent of total licks per day for sucrose or sucralose/saccharine. Data is given as Mean ± SEM. Data per graph were compared by 2-way ANOVA followed by Bonferroni multiple comparison, ***p < 0.001 vs. sucralose/saccharine.
Figure 4.
Figure 4.
Effect of an SGLT6 inhibitor on sucrose vs. sucralose preference in caloric restricted mice. Single housed mice were caloric restricted to decrease bodyweight by approx. 10% (n = 7–8/group) (a). Mice with reduced bodyweight were treated either with Cpd B (30 mg/kg, BID) or vehicle and received a choice between 100 mM sucrose and 3 mM sucralose for 2 consecutive days. Preference was assessed using a lickometer system recording licks per mouse. Data is presented as percent of total licks of 2 d for sucrose or sucralose (b). Data is given as Mean ± SEM (a, b). Data (a) were compared by Student t-test, data (b) were compared by 2-way ANOVA followed by Bonferroni multiple comparison test.
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