Dietary Tributyrin Supplementation Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Suckling Piglets with Intrauterine Growth Retardation

Abstract

Intrauterine growth retardation (IUGR) is associated with insulin resistance and lipid disorder. Tributyrin (TB), a pro-drug of butyrate, can attenuate dysfunctions in body metabolism. In this study, we investigated the effects of TB supplementation on insulin resistance and lipid metabolism in neonatal piglets with IUGR. Eight neonatal piglets with normal birth weight (NBW) and 16 neonatal piglets with IUGR were selected, weaned on the 7th day, and fed basic milk diets (NBW and IUGR groups) or basic milk diets supplemented with 0.1% tributyrin (IT group, IUGR piglets) until day 21 (n = 8). Relative parameters for lipid metabolism and mRNA expression were measured. Piglets with IUGR showed higher (P < 0.05) concentrations of insulin in the serum, higher (P < 0.05) HOMA-IR and total cholesterol, triglycerides (TG), non-esterified fatty acid (NEFA) in the liver, and lower (P < 0.05) enzyme activities (hepatic lipase [HL], lipoprotein lipase [LPL], total lipase [TL]) and concentration of glycogen in the liver than the NBW group. TB supplementation decreased (P < 0.05) the concentrations of insulin, HOMA-IR, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in the serum, and the concentrations of TG and NEFA in the liver, and increased (P < 0.05) enzyme activities (HL, LPL, and TL) and concentration of glycogen in the liver of the IT group. The mRNA expression for insulin signal transduction pathway and hepatic lipogenic pathway (including transcription factors and nuclear factors) was significantly (P < 0.05) affected in the liver by IUGR, which was efficiently (P < 0.05) attenuated by diets supplemented with TB. TB supplementation has therapeutic potential for attenuating insulin resistance and abnormal lipid metabolism in IUGR piglets by increasing enzyme activities and upregulating mRNA expression, leading to an early improvement in the metabolic efficiency of IUGR piglets.

Fig 1. mRNA expression for INSR, IRS1, PIK3C3, and Akt2 was normalized using GAPDH as the control.

Data are expressed as mean ± SEM, n = 6. SEM, standard error of mean. * indicates a significant difference from control group (P < 0.05). NBW, piglets with normal birth weight that were fed with basic milk diets; IUGR: piglets with intrauterine growth retardation that were fed with basic milk diets; IT, piglets with intrauterine growth retardation that were fed with diets supplemented with 0.1% tributyrin.

Fig 2. mRNA expression for SREBP-1, LXRα, PPARα, and FAT/CD36 was normalized using GAPDH as the control.

Data are expressed as mean ± SEM, n = 6. SEM, standard error of mean. * indicates a significant difference from control group (P < 0.05). NBW, piglets with normal birth weight that were fed with basic milk diets; IUGR: piglets with intrauterine growth retardation that were fed with basic milk diets; IT, piglets with intrauterine growth retardation that were fed with diets supplemented with 0.1% tributyrin.

Fig 3. mRNA expression of FAS, ACCβ, SCD, and FABP was normalized using GAPDH the control.

Data are expressed as mean ± SEM, n = 6. SEM, standard error of mean. * indicates a significant difference from control group (P < 0.05). NBW, piglets with normal birth weight that were fed with basic milk diets; IUGR: piglets with intrauterine growth retardation that were fed with basic milk diets; IT, piglets with intrauterine growth retardation that were fed with diets supplemented with 0.1% tributyrin.