Gama-aminobutyric acid (GABA) alleviates hepatic inflammation via GABA receptors/TLR4/NF-κB pathways in growing-finishing pigs generated by super-multiparous sows

Abstract

The offspring of super-multiparous sows face problems such as decreased growth performance, poor meat quality and even diseases in animal husbandry. Gama-aminobutyric acid (GABA) has long been known to promote growth and suppress inflammation, but little is known about the mechanisms. A total of 72 growing-finishing pigs from the 8th generation were randomly allotted to 2 groups with 6 replicates per treatment to receive a corn–soybean basal diet or the basal diet supplemented 20 mg/kg GABA for 60 d. After the animal-trial period, samples of serum and liver were collected for further analysis. Additionally, a lipopolysaccharide (LPS)-induced inflammatory model using HepG2 cells was established to explore the role of GABA on regulating hepatic inflammation. The results indicated that inflammatory cell infiltration occurs in the liver of progeny of super-multiparous sows, and dietary supplementation with GABA influenced liver morphology, increased activities of antioxidant enzymes and decreased the expression abundance of pro-inflammatory cytokines, including tumor necrosis factor-α (TNFα) and interleukin (IL)-1β, in the liver of growing-finishing pigs (P < 0.05). In addition, GABA supplementation increased mRNA expressions of peroxisome proliferator-activated receptor γ (PPARγ) and GABA receptors (GABARs), and reduced the expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling (P < 0.05). Additionally, an in vitro experiment demonstrated that GABA decreased the expressions of hepatic TLR4/NF-κB signaling via activating GABARs under LPS-stress (P < 0.05). In summary, liver injury may affect the growth performance of growing-finishing pigs by changing hepatic mitochondrial metabolism, the expression of pro-inflammatory cytokines and TLR4/NF-κB pathway and that GABA supplementation has a restorative effect by acting on GABARs.

Keywords

• Gama-aminobutyric acid
• Growing-finishing pig
• Liver inflammation
• Lipopolysaccharide
• NF-κB