Early high-energy diet induces a systemic metabolic alteration in light weaning body weight piglets that persists after dietary normalization

Light weaning body weight (LWBW) piglets exhibit inferior growth performance, and their energy requirement vary dynamically with increasing body weight. Although high-energy diets improve growth, they risk impairing liver health. Therefore, we investigated a multi-phase, high-net energy (HNE) regimen with stepwise-decreasing energy concentration with increasing body weight, assessing its impact on growth performance, liver health, and gut microbiota in LWBW piglets. Thirty LWBW piglets (28 days of age, initial body weight: 6.09 ± 0.47 kg) were randomly assigned to two groups; a high-net energy diet based on the energy requirement curve (HNE diet), and a low-net energy diet formulated according to NRC recommendations (NRC diet). Each treatment consisted of five physically separated pens (experimental unit and replicate, n = 5), with three piglets housed per pen throughout the 42-day trial. Results showed that the HNE diet tended to reduce feed to gain ratio (p = 0.075) but failed to improve average daily gain (ADG) in LWBW piglets. Relative to the NRC diet, the HNE diet exhibited significant elevations in serum concentrations of glucose, triglycerides, total cholesterol, bile acids, and alanine aminotransferase (p < 0.05), as well as in hepatic the content of malondialdehyde and the activity of total superoxide dismutase contents (p < 0.05). In addition, HNE diet upregulated the mRNA expression of lipogenic genes acetyl-CoA carboxylase (p < 0.05) and fatty acid synthase (p = 0.076), along with the protein levels of pro-inflammatory cytokines and endoplasmic reticulum stress marker glucose-regulated protein 78 (p < 0.05). Serum metabolomic profiling revealed that HNE diet induced alterations in a series of metabolites associated with oxidative stress, specifically increasing the concentrations of LysoPC, LysoPE, and guanosine while reducing levothyroxine abundance in LWBW piglets. Prevotella copri was the key microbe in the colon of HNE group piglets. Furthermore, HNE diet significantly elevated colonic concentrations of acetate, propionate, and butyrate (p < 0.05). Collectively, these findings suggest that the high-net energy diet reduced the feed-to-gain ratio, it did not significantly increase the ADG of piglets. This phenomenon may be associated with liver function and gut microbiota. Notably, the early high-net energy diet induces a systemic metabolic alteration that persists after dietary normalisation.