Gut Microbiota Is a Major Contributor to Adiposity in Pigs

Abstract

Different breeds of pigs vary greatly in their propensity for adiposity. Gut microbiota is known to play an important role in modulating host physiology including fat metabolism. However, the relative contribution of gut microbiota to lipogenic characteristics of pigs remains elusive. In this study, we transplanted fecal microbiota of adult Jinhua and Landrace pigs, two breeds of pigs with distinct lipogenic phenotypes, to antibiotic-treated mice. Our results indicated that, 4 weeks after fecal transplantation, the mice receiving Jinhua pigs' "obese" microbiota (JM) exhibited a different intestinal bacterial community structure from those receiving Landrace pigs' "lean" microbiota (LM). Notably, an elevated ratio of Firmicutes to Bacteroidetes and a significant diminishment of Akkermansia were observed in JM mice relative to LM mice. Importantly, mouse recipients resembled their respective porcine donors in many of the lipogenic characteristics. Similar to Jinhua pig donors, JM mice had elevated lipid and triglyceride levels and the lipoprotein lipase activity in the liver. Enhanced expression of multiple key lipogenic genes and reduced angiopoietin-like 4 (Angptl4) mRNA expression were also observed in JM mice, relative to those in LM mice. These results collectively suggested that gut microbiota of Jinhua pigs is more capable of enhancing lipogenesis than that of Landrace pigs. Transferability of the lipogenic phenotype across species further indicated that gut microbiota plays a major role in contributing to adiposity in pigs. Manipulation of intestinal microbiota will, therefore, have a profound impact on altering host metabolism and adipogenesis, with an important implication in the treatment of human overweight and obesity.

Keywords: adipogenesis; fat metabolism; fecal microbiota transplantation; microbiota; obesity; pigs.

FIGURE 1

Fat deposition and lipogenesis in the liver of Landrace and Jinhua pigs. (A) Representative pictures of the liver sections of Landrace and Jinhua pigs stained with Oil Red O. Neutral lipids appear in red (magnification: 400×). (B) Relative triglyceride content (%) in the liver of Landrace and Jinhua pigs. (C) Relative expression levels of several major lipogenic genes in the liver of two breeds of pigs. (D) The lipoprotein lipase activity in the liver of Landrace and Jinhua pigs. The results were shown as means ± SEM of 10 pigs. ^∗P < 0.05 (by unpaired Student’s t-test).

FIGURE 2

Fat deposition and lipogenesis in the abdominal fat tissue of Landrace and Jinhua pigs. (A) Representative pictures of the abdominal fat sections stained with hematoxylin and eosin (magnification: 200×). (B) Relative expression levels of several major lipogenic genes in the abdominal fat of two breeds of pigs. (C) The lipoprotein lipase activity in the abdominal fat of Landrace and Jinhua pigs. The results were shown as means ± SEM of 10 pigs. ^∗P < 0.05 (by unpaired Student’s t-test).

FIGURE 3

Relative ANGPTL4 mRNA expression levels in the intestinal tract (A) and liver and abdominal fat (B) of Landrace and Jinhua pigs. The results were shown as means ± SEM of 10 pigs. ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001 (by unpaired Student’s t-test).

FIGURE 4

The composition of the fecal bacterial community in Jinhua and Landrace donor pigs at the phylum (A) and genus (B) levels. Only top 5 phyla and top 10 genera are shown.

FIGURE 5

Cecal bacterial community structure of mouse recipients at the phylum (A) and genus (B) levels. Only top 5 phyla and top 10 genera are shown. JM, mice receiving fecal microbiota from Jinhua pigs; LM, mice receiving fecal microbiota from Landrace pigs.

FIGURE 6

Principal coordinates analysis (PCoA) of the cecal bacterial community composition of mouse recipients based on weighted unifrac distance. JD, Jinhua pig donor; LD, Landrace pig donor; JM, mice receiving fecal microbiota from Jinhua pigs; LM, mice receiving fecal microbiota from Landrace pigs.

FIGURE 7

Initial (A) and final body weight (BW) (B) and daily weight gain (C) of mice receiving fecal microbiota of Landrace and Jinhua pigs. The horizontal line in each group denotes the average value of six mice. JM, mice receiving fecal microbiota from Jinhua pigs; LM, mice receiving fecal microbiota from Landrace pigs. Statistical analysis was conducted using unpaired Student’s t-test and the significance values were indicated.

FIGURE 8

Fat deposition and lipogenesis in the liver of mice transplanted with Landrace and Jinhua pig microbiota. (A) Representative pictures of the liver sections of mouse recipients stained with Oil Red O. Neutral lipids appear in red (magnification: 400×). (B) Relative triglyceride content (%) in the liver of mouse recipients. (C) Relative expression levels of several major lipogenic genes in the liver of mouse recipients. (D) The lipoprotein lipase activity in the liver of mouse recipients. The results were shown as means ± SEM of 12 mice. ^∗P < 0.05 (by unpaired Student’s t-test). LM, mice receiving fecal microbiota from Landrace pigs; JM, mice receiving fecal microbiota from Jinhua pigs.

FIGURE 9

Fat deposition and lipogenesis in the abdominal fat tissue of mouse recipients. (A) Representative pictures of the abdominal fat sections stained with hematoxylin and eosin (magnification: 200×). (B) Relative expression levels of several major lipogenic genes in the abdominal fat of mice transplanted with Landrace and Jinhua pig microbiota. (C) The lipoprotein lipase activity in the abdominal fat of mouse recipients. The results were shown as means ± SEM of 12 mice. ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001 (by unpaired Student’s t-test). LM, mice receiving fecal microbiota from Landrace pigs; JM, mice receiving fecal microbiota from Jinhua pigs.

FIGURE 10

Relative Angptl4 mRNA expression levels in the intestinal tract (A) and the liver and abdominal fat (B) of mouse recipients. The results were shown as means ± SEM of 12 mice. ^∗P < 0.05, ^∗∗P < 0.01, and ^∗∗∗P < 0.001 (by unpaired Student’s t-test). LM, mice receiving fecal microbiota from Landrace pigs; JM, mice receiving fecal microbiota from Jinhua pigs.