Insulin resistance and dyslipidemia in low-birth-weight goat kids

Abstract

Low birth weight (LBW) impairs the development and health of livestock by affecting postnatal growth performance and metabolic health in adulthood. Previous studies on indigenous goats in southwest China showed that LBW goat kids had higher mortality and morbidity rates, including hepatic dyslipidemia and liver damage. However, the mechanism of insulin resistance affecting lipid metabolism under LBW conditions remains unclear. In this study, we conducted in vivo glucose-insulin metabolic studies, measured biochemical parameters, and analyzed related regulatory pathways. Both glucose tolerance tests and insulin tolerance tests indicated insulin resistance in LBW goat kids compared to controls (p < 0.05). The marker of insulin resistance, homeostasis model assessment (HOMA), was 2.85-fold higher in LBW than in control goats (p < 0.01). Additionally, elevated levels of free fatty acids in both plasma and skeletal muscle were observed in LBW goats compared to normal birth weight (NBW) goats (p < 0.05). Transcriptome analysis revealed impairments in lipid metabolism and insulin signaling in LBW goats. The observed lipid accumulation was associated with the upregulation of genes linked to fatty acid uptake and transport (FABP3), fatty acid oxidation (PPARA), triacylglycerol synthesis (LPIN1 and DGAT1), oxidative stress (ANKRD2), and insulin resistance (PGC1α). Furthermore, the insulin receptor substrate 2 (IRS2) was lower in the liver of LBW goat kids (p < 0.05). While there was no change in insulin function in skeletal muscle, LBW may lead to lipid accumulation in skeletal muscle by interfering with insulin function in the liver. These findings collectively impact the health and growth performance of livestock.

Keywords: goat; insulin resistance; lipid accumulation; low birth weight; skeletal muscle.

Figure 1

(A) Schematic diagram of the experimental design and in vivo animal studies. (B) Growth rate in newborn goats. GTT, glucose tolerance test; ITT, insulin tolerance test. Birth weight for control (□, n = 10) and LBW goat kids (•, n = 8) are presented for their 6 to 25 days of postnatal life.

Figure 2

Glucose and insulin tolerance tests. During glucose tolerance test, concentration of blood glucose (n = 5) (A) was not different from both groups, but plasma insulin (n = 5) (B) and area under the curve of insulin (n = 5) (C) were significantly higher in LBW goat kids compared to control. LBW group exhibited lower disposal rate of glucose level (control, n = 6; LBW, n = 7) (D and E) and HOMA (F) during insulin tolerance test (n = 5).^†P < 0.1; *P < 0.05; **P < 0.01.

Figure 3

(A) Metabolic features of free fatty acids in plasma (n = 5); (B) intramuscular triglyceride (control, n = 5; LBW, n = 6); (C) intramuscular glycogen (control, n = 6; LBW, n = 7); (D) intramuscular free fatty acids content (control, n = 5; LBW, n = 6). (E) Pearson correlation analysis of all samples (control, n = 3; LBW, n = 4). (F) Volcano plot of global genes expression. (G) Cluster heatmap of differential expressed genes in semitendinosus. *P < 0.05; **P < 0.01. FFA, free fatty acids; LBW, low birth weight.

Figure 4

(A) KEGG pathway enrichment analysis of DEGs (control, n = 3; LBW, n = 4). (B) Fold changes in the genes with the greatest expression change in skeletal muscle. (C) Gene expression determined by RNAseq reflects real-time qPCR (control, n = 6; LBW, n = 7). (D) Differential genes associated with insulin function (control, n = 6; LBW, n = 7). (E) mRNA expression levels in skeletal muscle of control and LBW (control, n = 6; LBW, n = 7). *P < 0.05;^†P < 0.1.

Figure 5

Effects of birth weight on mRNA levels of genes related to fatty acid metabolism. (A) Triglyceride decomposition (ATGL) (n = 4); (B) fatty acid oxidation (CPTI1 and PPARA) (n = 4); (C) triglyceride synthesis (LPIN1 and DGAT1) (n = 4); (D) de novo synthesis of fatty acid (FASN, ACACA, and SCD1) (n = 4); (E) lipid droplet synthesis (PLIN3) (control, n = 4; LBW, n = 3). (F) Relative fold changes for insulin signaling and glucose uptake pathways in liver (n = 5). *P < 0.05; **P < 0.01.

Figure 6

LBW goats contributed to hepatic insulin resistance and had higher FFA in skeletal muscle.