Systemic administration of IL-10 diminishes SPX-induced fat accumulation, infiltration of macrophages, and pro-inflammatory responses in the islets.

<p>(<b>A</b>) Representative images of CD11c staining (upper sections) and CD206 staining (lower sections) in intra-islet areas in pancreas sections from each group. Scale bar = 100 µm. (<b>B−D</b>) CD11c-positive areas (<b>B</b>), CD206-positive areas (<b>C</b>), and M1/M2 ratios (<b>D</b>) in the islets in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Standard-Sham group, ^#<i>P</i><0.05 vs. the HF-Sham group. (<b>E</b>) Serum levels of IL-1β, MCP-1 and IL-10 in sham and SPX mice fed standard chow or a HF diet. *<i>P</i><0.05 vs. the Standard-Sham group, ^#<i>P</i><0.05 vs. the Standard-SPX group. (<b>F</b>) Serum cytokine changes relative to the Standard-Sham group. *<i>P</i><0.05 vs. IL-1β and MCP-1. (<b>G</b>) Serum leptin levels in each group (n = 6). *<i>P</i><0.05 vs. the Standard-Sham group, ^#<i>P</i><0.05 vs. the HF-Sham group, ^$<i>P</i><0.05 vs. the HF-SPX group. Treatment groups: Standard-Sham, fed standard chow, given serum albumin, and sham-operated; HF-Sham, fed a HF diet, administered serum albumin, and sham-operated; HF-SPX, fed a HF diet, given serum albumin, and splenectomized; HF-SPX+IL-10, fed a HF diet, given IL-10, and splenectomized; Pair-fed, administered serum albumin, sham-operated, and fed the same amount of food as that consumed by the HF-SPX group.</p

SPX has little effect on the infiltration of macrophages in islets of IL-10-deficient mice.

<p>(<b>A and B</b>) Representative images of CD11c staining (<b>A</b>) and CD206 staining (<b>B</b>) in intra-islet areas of pancreas sections from each group. Scale bar = 100 µm. (<b>C−E</b>) CD11c-positive areas (<b>C</b>), CD206-positive areas (<b>D</b>), and M1/M2 ratios (<b>E</b>) in the islets in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Sham group (wild-type or IL-10KO mice), ^#<i>P</i><0.05 vs. SPX mice (wild-type). Treatment groups: Sham, fed a HF diet, given serum albumin, and sham-operated; SPX, fed a HF diet, given serum albumin, and splenectomized; SPX+IL-10, fed a HF diet, given recombinant mouse IL-10, and splenectomized. Wild-type, wild-type mice; IL-10KO, IL-10-deficient mice.</p

Effects of SPX on the infiltration of M1 and M2 macrophages and on inflammatory responses in the pancreas.

<p>(<b>A and B</b>) Representative images of CD11c staining (left) and CD206 staining (right) in intra-islet areas (<b>A</b>) and intra-lobular areas (<b>B</b>) in pancreas sections from each group. (<b>C−E</b>) Percentage of CD11c-positive area (<b>C</b>) and CD206-positive area (<b>D</b>) and M1/M2 ratio (<b>E</b>) in intra-islet areas. (<b>F−H</b>) Percentage of CD11c-positive area (<b>F</b>) and CD206-positive area (<b>G</b>) and M1/M2 ratio (<b>H</b>) in intra-lobular areas. (<b>J and K</b>) Content of pro- and anti-inflammatory cytokines (<b>J</b>) and interleukin (IL)-10/IL-1β ratio (<b>K</b>) in the pancreas in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Standard-Sham group. Scale bar = 100 µm. Treatment groups: Standard-Sham, fed standard chow and sham-operated; Standard-SPX, fed standard chow and splenectomized.</p

Effects of SPX on islets and fat accumulation in the pancreas.

<p>(<b>A</b>) Representative images of insulin staining (left), Mallory-Azan staining (middle), and H&E staining (right) of pancreas sections from mice in each group. (<b>B−E</b>) Insulin staining area (<b>B</b>), intra-islet fibrosis area (<b>C</b>), intra-lobular fibrosis area (<b>D</b>), hydroxyproline content (<b>E</b>), α-SMA-positive cells (<b>F</b>), TG content (<b>G</b>) in the pancreas and serum leptin level (<b>H</b>) in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Standard-Sham group. Scale bar = 100 µm. Treatment groups: Standard-Sham, fed standard chow and sham-operated; Standard-SPX, fed standard chow and splenectomized.</p

Effects of a HF diet on splenic and serum levels of pro- and anti-inflammatory cytokines.

<p>Protein levels of IL-1β, MCP-1, and IL-10 in the spleen and serum from each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Standard group. Treatment groups: Standard, fed standard chow and sham-operated; HF, fed a HF diet and sham-operated.</p

SPX has little effect on changes in the pancreatic islets in IL-10-deficient mice.

<p>(<b>A</b>) Representative images of insulin staining (left), Mallory-Azan staining (middle), and α-SMA staining (right) in pancreas sections from each group. Scale bar = 100 µm. (<b>B−F</b>) Insulin-staining area in the pancreas (<b>B</b>), intra-islet fibrosis area (<b>C</b>) and intra-lobular fibrosis area (<b>D</b>), hydroxyproline content (<b>E</b>) and α-SMA-positive cells (<b>F</b>) in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Sham group (wild-type or IL-10KO mice), ^#<i>P</i><0.05 vs. SPX mice (wild-type). Treatment groups: Sham, fed a HF diet, given serum albumin and sham-operated; SPX, fed a HF diet, given serum albumin, and splenectomized; SPX+IL-10, fed a HF diet, given recombinant mouse IL-10 and splenectomized. Wild-type, wild-type mice; IL-10KO, IL-10-deficient mice.</p

SPX has little effect on the infiltration of macrophages in intra-lobular area of IL-10-deficient mice.

<p>(<b>A and B</b>) Representative images of CD11c staining (<b>A</b>) and CD206 staining (<b>B</b>) in intra-lobular areas in pancreas sections from each group. Scale bar = 100 µm. (<b>C−E</b>) CD11c-positive areas (<b>C</b>), CD206-positive areas (<b>D</b>), and M1/M2 ratios (<b>E</b>) in intra-lobular areas in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Sham group (wild-type or IL-10KO mice), ^#<i>P</i><0.05 vs. SPX mice (wild-type). Treatment groups: Sham, fed a HF diet, given serum albumin, and sham-operated; SPX, fed a HF diet, given serum albumin, and splenectomized; SPX+IL-10, fed a HF diet, given recombinant mouse IL-10, and splenectomized. Wild-type, wild-type mice; IL-10KO, IL-10-deficient mice.</p

Systemic administration of IL-10 diminishes SPX-induced alterations in pancreatic islets.

<p>(<b>A</b>) Representative images of insulin staining (left) and Mallory-Azan staining (right) in pancreas sections from each group. Scale bar = 100 µm. (<b>B−F</b>) Insulin-staining area (<b>B</b>), intra-islet (<b>C</b>) and intra-lobular (<b>D</b>) fibrosis area, hydroxyproline content (<b>E</b>) and α-SMA-positive cells (<b>F</b>) in the pancreas in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Sham-Standard group, ^#<i>P</i><0.05 vs. the Sham-HF group. Treatment groups: Standard-Sham, fed standard chow, given serum albumin, and sham-operated; HF-Sham, fed a HF diet, administered serum albumin, and sham-operated; HF-SPX, fed a HF diet, given serum albumin, and splenectomized; HF-SPX+IL-10, fed a HF diet, given IL-10, and splenectomized; Pair-fed, administered serum albumin, sham-operated, and fed the same amount of food as that consumed by the HF-SPX group.</p

SPX has little effect on pro-inflammatory cytokines in the pancreas of IL-10-deficient mice.

<p>Pancreatic content of pro-inflammatory cytokines in each group (<i>n</i> = 6). *<i>P</i><0.05 vs. the Sham group (wild-type or IL-10KO mice). Treatment groups: Sham, fed a HF diet, given serum albumin, and sham-operated; SPX, fed a HF diet, given serum albumin, and splenectomized; SPX+IL-10, fed a HF diet, given recombinant mouse IL-10, and splenectomized. Wild-type, wild-type mice; IL-10KO, IL-10-deficient mice.</p

Effects of splenectomy on daily food intake, body weight, epididymal WAT weight, serum adiponectin levels, glucose and lipid metabolism.

*<p><i>P</i><0.05 vs. the Standard-Sham group. Treatment groups: Standard-Sham, fed standard chow and sham-operated (<i>n</i> = 6); Standard-SPX, fed standard chow and splenectomized (<i>n</i> = 6).</p