Soy protein in the prevention of hepatic steatosis in obese OLETF rats

Soy protein has shown beneficial effects on hepatic lipid metabolism and prevention of hepatic steatosis. Here we sought to test our hypothesis that a soy protein versus dairy protein‐based diet would significantly improve hepatic mitochondrial function and attenuate hepatic steatosis development in hyperphagic Otsuka Long‐Evans Tokushima Fatty (OLETF) rats. Five week old male OLETF rats were randomized to isocaloric diets containing 21% kcal as protein from milk protein isolate (MPI), soy protein isolate (SPI), or 50:50 MPI/SPI (M/S) (N=9–10/group) for 16 weeks. SPI significantly (p<0.05) attenuated fat mass and percent body fat by ~10% compared with M/S, but did not differ from MPI. Cumulative food intake was not different between SPI and other groups, but was significantly less in MPI rats compared with M/S (p<0.05), which corresponded with lowered serum insulin (p<0.05 vs SPI and M/S); serum glucose did not differ among groups. SPI reduced serum cholesterol and serum thiobarbituric acid reactive substances (TBARS) content (p<0.05) and tended to lower serum free fatty acids and increase serum antioxidant capacity compared with the other groups (p=0.1). Histological examination of liver revealed significant attenuation (p<0.05) in hepatic steatosis in the SPI group compared with MPI and M/S and biochemical assessment of liver triglyceride content showed a similar trend. Lipidomics analyses also indicated significant reductions (p<0.05) in hepatic diacylglycerols and phosphatidylcholine in SPI vs MPI. Intriguingly, reduced hepatic steatosis with SPI was associated with dramatic reductions in markers of hepatic de novo lipogenesis (acetyl‐coA carboxylase and fatty acid synthase protein content) but not with improvements in hepatic mitochondrial content or function. In fact, MPI livers displayed higher hepatic mitochondrial respiration, β‐hydroxy‐acyl‐CoA dehydrogenase activity and citrate synthase activity (p<0.05) compared with SPI and M/S groups. Furthermore, milk protein and soy protein appear to impact different pathways in hepatic lipid metabolism, with milk protein upregulating hepatic mitochondrial content/function and soy protein downregulating hepatic de novo lipogenesis. In summary, soy protein may be more beneficial than milk protein in the attenuation of hepatic steatosis development in hyperphagic obese OLETF rats. Support or Funding Information Support: MU School of Medicine Summer Research Fellowship (CMS), DuPont Nutrition & Health, NIH R01DK088940 (JPT) and VHA‐CDA2 IK2BX001299 (RSR).