Dietary alpha-ketoglutarate alleviates Escherichia coli LPS-induced intestinal barrier injury by modulating the endoplasmic reticulum-mitochondrial system pathway in piglets.

BACKGROUND: Alpha-ketoglutarate (AKG) plays a pivotal role in mitigating inflammation and enhancing intestinal health.

OBJECTIVE: This study aimed to investigate whether AKG could protect against lipopolysaccharide (LPS)-induced intestinal injury by alleviating disorders in mitochondria-associated endoplasmic reticulum membranes, dysfunctional mitochondrial dynamics, and endoplasmic reticulum stress in a piglet model.

METHODS: Twenty-four piglets were subjected to a 2 × 2 factorial design, with dietary factors (basal diet or 1% AKG diet) and LPS treatment (LPS or saline). After 21 days of consuming either the basal diet or AKG diet, piglets received injections of LPS or saline. The experiment was divided into four treatment groups (Control group, basal diet + saline; LPS group, basal diet +LPS; AKG group, AKG diet + saline; AKG_LPS group, AKG + LPS), each consisting of six piglets.

RESULTS: The results demonstrated that, compared to the control group, AKG enhanced jejunal morphology, antioxidant capacity, as well as the mRNA and protein expression of tight junction proteins. Moreover, it has shown a reduction in serum diamine oxidase activity and D-lactic acid content in piglets. Additionally, fewer disorders in the endoplasmic reticulum-mitochondrial system were reflected by AKG, as evidenced by AKG regulating the expression of key molecules of mitochondrial dynamics (mitochondrial calcium uniporter, optic atrophy 1, fission 1, and dynamin-related protein 1), endoplasmic reticulum stress (activating transcription factor 4, activating transcription factor 6, C/EBP homologous protein, eukaryotic initiation factor 2α, glucose-regulated protein 78, protein kinase R-like endoplasmic reticulum kinase), and mitochondria-associated endoplasmic reticulum membranes (mitofusin-1, mitofusin-2, glucose-regulated protein 75, and voltage-dependent anion channel-1).

CONCLUSIONS: Dietary AKG can prevent mitochondrial dynamics dysfunction, endoplasmic reticulum stress, and mitochondria-associated endoplasmic reticulum membranes disorder, ultimately alleviating LPS-induced intestinal damage in piglets.