Alpha-ketoglutarate (AKG) lowers body weight and affects intestinal innate immunity through influencing intestinal microbiota

Abstract

Alpha-ketoglutarate (AKG), a precursor of glutamate and a critical intermediate in the tricarboxylic acid cycle, shows beneficial effects on intestinal function. However, the influence of AKG on the intestinal innate immune system and intestinal microbiota is unknown. This study explores the effect of oral AKG administration in drinking water (10 g/L) on intestinal innate immunity and intestinal microbiota in a mouse model. Mouse water intake, feed intake and body weight were recorded throughout the entire experiment. The ileum was collected for detecting the expression of intestinal proinflammatory cytokines and innate immune factors by Real-time Polymerase Chain Reaction. Additionally, the ileal luminal contents and feces were collected for 16S rDNA sequencing to analyze the microbial composition. The intestinal microbiota in mice was disrupted with an antibiotic cocktail. The results revealed that AKG supplementation lowered body weight, promoted ileal expression of mammalian defensins of the alpha subfamily (such as cryptdins-1, cryptdins-4, and cryptdins-5) while influencing the intestinal microbial composition (i.e., lowering the Firmicutes to Bacteroidetes ratio). In the antibiotic-treated mouse model, AKG supplementation failed to affect mouse body weight and inhibited the expression of cryptdins-1 and cryptdins-5 in the ileum. We concluded that AKG might affect body weight and intestinal innate immunity through influencing intestinal microbiota.

Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation

“…The serum AKG level was tested at 0, 1, 2, 4, and 6 h after gavage (n = 8 per group). ª 2020 The Authors The EMBO Journal 39: e103304 | 2020 (Chen et al, 2017). Moreover, we confirmed that acute oral administration resulted in increased circulating AKG (Fig 2A).…”

“…It has been shown that AKG lowered mouse body weight through influencing intestinal microbiota (Chen et al, 2017), suggesting another alternative mechanism for anti-obesity effects of AKG. On ▸ Figure 3.…”

Effect of dietary α‐ketoglutarate and allicin supplementation on the composition and diversity of the cecal microbial community in growing pigs

“…It is well known that treatment with antibiotics results in dysbiosis by decreasing diversity and taxonomic richness, shifting metabolic capacity, and reducing resistance to colonization . Conversely, our previous studies demonstrated that dietary AKG enhanced beneficial bacterial species and improved the composition of the intestinal microbiota in pig and mouse models . The mechanism might be that AKG served as a major energy source for intestinal microbiota and epithelial cells .…”

“…33 Conversely, our previous studies demonstrated that dietary AKG enhanced beneficial bacterial species and improved the composition of the intestinal microbiota in pig and mouse models. 34,35 The mechanism might be that AKG served as a major energy source for intestinal microbiota and epithelial cells. 27,35 Our previous report showed that dietary AKG improved energy metabolism in the small intestine of piglets.…”

α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation

“…If AKG plays a physiological role in exercise-induced beneficial effects, AKG supplementation will mimic some of the metabolic effects of exercise. Water supplementation of AKG is well tolerated (Chen et al, 2017). Moreover, we confirmed that acute oral administration resulted in increased circulating AKG (Fig.…”