Dietary α-Ketoglutarate Alleviates Escherichia coli LPS-Induced Intestinal Barrier Injury by Modulating the...

Area of Science:

• Gastroenterology
• Cell Biology
• Nutritional Science

Background:

• α-Ketoglutarate (AKG) is recognized for its anti-inflammatory properties and role in maintaining intestinal health.
• Intestinal injury can result from disruptions in mitochondria-associated endoplasmic reticulum (MAM) membranes, mitochondrial dynamics, and endoplasmic reticulum (ER) stress.

Purpose of the Study:

• To evaluate the protective effects of dietary AKG against lipopolysaccharide (LPS)-induced intestinal injury in piglets.
• To investigate AKG's impact on MAM membrane integrity, mitochondrial dynamics, and ER stress.

Main Methods:

• A 2x2 factorial design study involving 24 piglets, with dietary treatments of basal diet or 1% AKG diet and LPS or saline injection.
• Piglets were divided into four groups: control, LPS, AKG, and AKG+LPS, with 6 piglets per group for 21 days.

Main Results:

• AKG supplementation enhanced jejunal morphology, antioxidant capacity, and tight junction protein expression while reducing serum diamine oxidase and D-lactic acid levels.
• AKG regulated key molecules involved in mitochondrial dynamics, ER stress, and MAM membranes, indicating reduced ER-mitochondrial system dysfunction.
• Specific molecular targets regulated by AKG included those related to mitochondrial calcium uptake, ER stress markers (ATF4, GRP78), and MAM proteins (Mfn-1, Mfn-2).

Conclusions:

• Dietary AKG effectively prevents mitochondrial dynamic dysfunction, ER stress, and MAM membrane disorders.
• AKG alleviates LPS-induced intestinal damage in piglets by restoring cellular homeostasis in the ER-mitochondrial system.
• AKG shows potential as a nutritional strategy to improve gut health and resilience against inflammatory insults.