Simple SummaryAlpha-ketoglutarate (AKG) is a critical intermediate in the tricarboxylic acid cycle. AKG has been reported to participate in energy production, promote protein synthesis, and improve amino acid metabolism. However, whether AKG functionally participates in the regulation of fat metabolism remains unknown. The objective of this experiment was to evaluate the impact of dietary supplementation with AKG on lipid metabolism in a pig model. The present results suggest that AKG supplementation in a reduced-protein diet could increase the intramuscular fat (IMF) and monounsaturated fatty acid (MUFA) contents in the biceps femoris muscles of pigs. These effects could be linked to the altered lipid metabolism related gene mRNA expression, which promotes the absorption and deposition of fatty acids in the muscle tissues. The results of this study can provide better understanding of the mechanisms by which dietary AKG modulates muscle lipid metabolism in pigs, and this could help to improve pig feeding strategies and supply high-quality pork for humans.AbstractThe aim of the current study was to investigate whether dietary supplementation with alpha-ketoglutarate (AKG) in a reduced crude protein (CP) diet would affect fatty acid composition and lipid metabolism related gene expression in the muscles of growing pigs. A total of 27 Large White × Landrace growing pigs at 44 ± 1 d of age (11.96 ± 0.18 kg) were randomly allocated to three treatments (n = 9). Dietary treatments included: (1) normal protein diet with 20% crude protein (CP) (NP); (2) a low crude protein diet formulated to contain approximately 17% CP (LP); and (3) a low crude protein diet with 17% CP supplemented with 1% AKG at the expense of regular corn components (ALP). The experimental trial lasted 35 d. The results showed that compared with the NP and LP diets, supplementation with AKG in a low-protein diet increased the intramuscular fat (IMF), oleic acid (C18:1n-9), and monounsaturated fatty acid (MUFA) contents (p < 0.05), and tended to increase the percentage of palmitoleic acid (C16:1) and stearic acid (C18:0) (p < 0.10) in the biceps femoris and longissimus dorsi muscles of growing pigs. These effects may be associated with increased relative mRNA expression levels of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipocyte determination and differentiation factor 1 (ADD1), fatty acid binding protein 4 (FABP4), and stearoyl-CoA desaturase (SCD) in skeletal muscle, indicating that AKG might be involved in the differential regulation of some key lipogenic genes in skeletal muscles of pigs.