Effects of Soy Protein on Liver and Adipose Tissue Inflammation and Gut Microbiota in Mice Fed with Ketogenic Diets.

Background: Studies on ketogenic diets with a higher percentage of fat composition have revealed conflicting results regarding the modulation of lipid metabolism and tissue inflammation. Furthermore, studies on soy protein consumption in ketogenic diets remain limited. In this study, the effects of ketogenic diets on hepatic and adipose tissue inflammation and of soy protein replacement in ketogenic diets were investigated. Methods: Mice were randomly assigned to a control diet (C), ketogenic diet (KD), or ketogenic with soy protein (KS) groups for an 18-week experiment. Both ketogenic diet groups were fed a low-carbohydrate, high-fat diet during the first 12 weeks and a ketogenic diet during the last 6 weeks of the experiment. The KS group was fed the same diet as the KD group, but soy protein was substituted for casein during the last 6 weeks. Results: The KD and KS groups exhibited higher plasma β-hydroxybutyrate levels; a higher incidence of hyperlipidemia; and lower blood glucose, mesenteric fat mass, adipose tissue TNF-α, IL-1β levels, and NLRP3 protein expression compared with the C group. In the gut microbiota analysis, the KD group had a higher F-B ratio than the C group. Greater A. muciniphila abundance and a lower F-B ratio were noted in the KS group compared with the KD group. Conclusions: Although ketogenic diets decreased mesenteric fat mass and adipose tissue inflammation and modulated NLRP3 expression, they were associated with hepatic inflammation and gut dysbiosis. Soy protein consumption in a ketogenic diet did not differ from casein consumption regarding diet-induced tissue inflammation, but it may have altered the gut microbiota.