Background:Previous studies have shown that exogenous short-chain fatty acids (SCFAs) introduction attenuated the body fat deposition in conventional mice and pigs. However, limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota. This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free (GF) pig model. Methods:Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators. All pigs were hand-fed with sterile milk powder for 21 d, then the sterile feed was introduced to pigs for another 21 d. In the second 21-d period, six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group, while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture (acetic, propionic, and butyric acids, 45, 15, and 11 mmol/L, respectively) per day and regarded as FA group. Results:Orally administrated with SCFAs tended to increase the adiponectin concentration in serum, enhance the CPT-1 activity in longissimus dorsi, and upregulate the ANGPTL4 mRNA expression level in colon (P<0.10). Meanwhile, the mRNA abundances of ACC, FAS, and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased (P<0.05) compared with those in the GF group. Besides, the mRNA expression of PGC-1αin liver and LPL in longissimus dorsi tended to (P<0.10) upregulate and downregulate respectively in the FA group. Moreover, oral administration of SCFAs tended to increase the protein level of GPR43 (P<0.10) and decrease the protein level of ACC (P<0.10) in liver. Also, oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver (P<0.05). In addition, the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted (P<0.05) by oral administration of SCFAs. Conclusions:Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model, which occurred independently of the gut microbiota.