Xylobiose Prevents High-Fat Diet Induced Mice Obesity by Suppressing Mesenteric Fat Deposition and Metabolic Dysregulation

Abstract

Obesity is a public concern and is responsible for various metabolic diseases. Xylobiose (XB), an alternative sweetener, is a major component of xylo-oligosaccharide. The purpose of this study was to investigate the effects of XB on obesity and its associated metabolic changes in related organs. For these studies, mice received a 60% high-fat diet supplemented with 15% d-xylose, 10% XB, or 15% XB as part of the total sucrose content of the diet for ten weeks. Body weight, fat and liver weights, fasting blood glucose, and blood lipids levels were significantly reduced with XB supplementation. Levels of leptin and adipokine were also improved and lipogenic and adipogenic genes in mesenteric fat and liver were down-regulated with XB supplementation. Furthermore, pro-inflammatory cytokines, fatty acid uptake, lipolysis, and β-oxidation-related gene expression levels in mesenteric fat were down-regulated with XB supplementation. Thus, XB exhibited therapeutic potential for treating obesity which involved suppression of fat deposition and obesity-related metabolic disorders.

Keywords: adipogenesis; inflammation; lipogenesis; mesenteric adipose tissue; obesity; xylobiose.

Figure 1

Effect of XB on body weight (b.w.) changes. b.w. of the five experimental groups are presented longitudinally. Ctrl, control mice that received the AIN93G diet; HF, obesity control mice that received a HFD; Xylo 15, mice that received a HFD with 15% of the total sucrose replaced with d-xylose; XB 10, mice that received a HFD with 10% of the total sucrose replaced with xylobiose; XB 15, mice that received a HFD with 15% of the total sucrose replaced with xylobiose.

Figure 2

Effects of XB on the expressions of genes related to adipogenesis, lipogenesis, and energy metabolism in mesenteric adipose tissue. Real-time PCR was performed to detect mRNA levels of adipogenesis and lipogenesis-related genes in mesenteric adipose tissues. (A) PPARγ; (B) C/EBPα; (C) SREBP-1c; (D) FAS; (E) ACC and β-oxidation-related genes; (F) ACO; (G) CPT1A; and (H) UCP2. Detection of GAPDH was performed as a loading control. The values presented are the mean ± SEM and all of the data were analyzed with one-way ANOVA and Newman-Keuls’ post hoc test. The superscript letters indicate significant differences (p < 0.05). PPARγ, peroxisome proliferator-activated receptor gamma; C/EBPα, CCAAT/enhancer binding protein alpha, SREBP-1c, sterol regulatory element-binding protein 1; FAS, fatty acid synthase; ACC, acetyl-CoA carboxylase; ACO, acyl-CoA oxidase; CPT1A, carnitine palmitoyltransferase I A; UCP2, uncoupling protein 2; GAPDH, Glyceraldehyde 3-phosphate dehydrogenase; Ctrl, control mice that received the AIN93G diet; HF, obesity control mice that received a HFD; Xylo 15, mice that received a HFD with 15% of the total sucrose replaced with d-xylose; XB 10, mice that received a HFD with 10% of the total sucrose replaced with xylobiose; XB 15, mice that received a HFD with 15% of the total sucrose replaced with xylobiose.

Figure 3

Effects of XB on the expressions of genes related to fatty acid uptake, lipolysis, and pro-inflammatory cytokines in mesenteric adipose tissues. Real-time PCR was performed to detect mRNA level of fatty acid uptake and lipolysis-related genes in mesenteric adipose tissues. (A) LPL; (B) CD36; and (C) HSL; (D) TNFα; (E) IL-1β; and (F) MCP-1. Detection of GAPDH was performed as a loading control. The values presented are the mean ± SEM and all of the data were analyzed with one-way ANOVA and Newman-Keuls’ post hoc test. The superscript letters indicate significant differences (p < 0.05). LPL, lipoprotein lipase; CD36, cluster of differentiation 36; HSL, hormone sensitive lipase; TNFα, tumor necrosis factor alpha; IL-1β, interleukin 1 beta; MCP-1, monocyte chemoattractant protein-1; Ctrl, control mice that received the AIN93G diet; HF, obesity control mice that received a HFD; Xylo 15, mice that received a HFD with 15% of the total sucrose replaced with D-xylose; XB 10, mice that received a HFD with 10% of the total sucrose replaced with xylobiose; XB 15, mice that received a HFD with 15% of the total sucrose replaced with xylobiose.

Figure 3

Effects of XB on the expressions of genes related to fatty acid uptake, lipolysis, and pro-inflammatory cytokines in mesenteric adipose tissues. Real-time PCR was performed to detect mRNA level of fatty acid uptake and lipolysis-related genes in mesenteric adipose tissues. (A) LPL; (B) CD36; and (C) HSL; (D) TNFα; (E) IL-1β; and (F) MCP-1. Detection of GAPDH was performed as a loading control. The values presented are the mean ± SEM and all of the data were analyzed with one-way ANOVA and Newman-Keuls’ post hoc test. The superscript letters indicate significant differences (p < 0.05). LPL, lipoprotein lipase; CD36, cluster of differentiation 36; HSL, hormone sensitive lipase; TNFα, tumor necrosis factor alpha; IL-1β, interleukin 1 beta; MCP-1, monocyte chemoattractant protein-1; Ctrl, control mice that received the AIN93G diet; HF, obesity control mice that received a HFD; Xylo 15, mice that received a HFD with 15% of the total sucrose replaced with D-xylose; XB 10, mice that received a HFD with 10% of the total sucrose replaced with xylobiose; XB 15, mice that received a HFD with 15% of the total sucrose replaced with xylobiose.

Figure 4

Effects of XB on lipid accumulation and lipogenesis in the liver. (A) Liver weight (g); (B) Liver triglyceride content (mg/g). (C) Hepatic histopathologic features (a) Ctrl; (b) HF; (c) Xylo 15; (d) XB 10; and (e) XB 15. Magnification ×200; (D–F) Real-time PCR results of adipogenesis and lipogenesis-related genes expression in the liver. The values presented are the mean ± SEM and all of the data were analyzed with one-way ANOVA and Newman-Keuls’ post hoc test. The superscript letters indicate significant differences (p < 0.05). PPARγ, peroxisome proliferator-activated receptor gamma; C/EBPα, CCAAT/enhancer binding protein alpha, SREBP-1c, sterol regulatory element-binding protein 1; Ctrl, control mice that received the AIN93G diet; HF, obesity control mice that received a HFD; Xylo 15, mice that received a HFD with 15% of the total sucrose replaced with d-xylose; XB 10, mice that received a HFD with 10% of the total sucrose replaced with xylobiose; XB 15, mice that received a HFD with 15% of the total sucrose replaced with xylobiose.

Figure 4

Effects of XB on lipid accumulation and lipogenesis in the liver. (A) Liver weight (g); (B) Liver triglyceride content (mg/g). (C) Hepatic histopathologic features (a) Ctrl; (b) HF; (c) Xylo 15; (d) XB 10; and (e) XB 15. Magnification ×200; (D–F) Real-time PCR results of adipogenesis and lipogenesis-related genes expression in the liver. The values presented are the mean ± SEM and all of the data were analyzed with one-way ANOVA and Newman-Keuls’ post hoc test. The superscript letters indicate significant differences (p < 0.05). PPARγ, peroxisome proliferator-activated receptor gamma; C/EBPα, CCAAT/enhancer binding protein alpha, SREBP-1c, sterol regulatory element-binding protein 1; Ctrl, control mice that received the AIN93G diet; HF, obesity control mice that received a HFD; Xylo 15, mice that received a HFD with 15% of the total sucrose replaced with d-xylose; XB 10, mice that received a HFD with 10% of the total sucrose replaced with xylobiose; XB 15, mice that received a HFD with 15% of the total sucrose replaced with xylobiose.

Figure 5

Proposed mechanism of xylobiose-regulated metabolic changes in obesity. Xylobiose suppresses adipogenesis, lipogenesis, lipolysis, and inflammation in mesenteric fat, and this reduces the release of FFAs and inflammatory cytokines to the portal vein. As a result, fat accumulation in the liver is suppressed. ACO, acyl-CoA oxidase; CD36, cluster of differentiation 36; C/EBPα, CCAAT/enhancer binding protein alpha; FAS, fatty acid synthase; FFA, free fatty acid; HSL, hormone-sensitive lipase; IL-1β, interleukin 1 beta; MCP-1, monocyte chemoattractant protein-1; LPL, lipoprotein lipase; PPARγ, peroxisome proliferator-activated receptor gamma; SREBP-1c, sterol regulatory element-binding protein 1; TG, triglyceride; TNFα, tumor necrosis factor alpha; VLDL, very low-density lipoprotein.