Limited preventive effects of empagliflozin against metabolic dysfunction-associated steatotic liver disease in a mouse model of fast food diet

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent disease with limited treatment options. The aim of this study was to evaluate the preventive effects of a sodium-glucose co-transporter (SGLT)-2 inhibitor, empagliflozin, on a dietary mouse model of MASLD.

In total, 24 C57BL/6 J mice of both sexes were randomly allocated to three groups, as follows: the fast food diet (FFD) group (eight mice, receiving a high-fat, high-cholesterol, high-fructose diet, FFD), the EMPA group (eight mice, fed a FFD with 10 mg/kg/d empagliflozin), and the chow diet (eight mice, CD) group. The mice were weighed and blood samples were drawn every 4 weeks; after 25 weeks the mice were euthanized, at which point liver tissues were histologically evaluated.

After 25 weeks, there was no significant difference in body weight between the three groups, whereas liver-to-body weight ratio was greater in the EMPA compared to the CD group (p = 0.002). Hepatic fibrosis was marginally different between the three groups (p = 0.045). Fibrosis stage 1 was present in five mice on FFD (62.5%), in one mouse on EMPA (12.5%), and in one mouse on CD (12.5%). Lipogenic, inflammatory, and fibrogenic genes did not differ between the EMPA and FFD groups. Interestingly, mRNA encoding for SGLT-1 and SGLT-2 was detected in the mouse livers.

Empagliflozin treatment in mice on a FFD did not result in any significant effects on morphological, biochemical, or histological features or on expression of hepatic genes associated with MASLD compared to those fed a FFD without empagliflozin. The observed effects on mild hepatic fibrosis warrant validation, possibly via studies of longer duration.