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High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

Gao M, Ma Y, Liu D - PLoS ONE (2015)

Bottom Line: Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride.Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1.Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, United States of America.

ABSTRACT
High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

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Gene expression analysis in WAT.(A) Expression level of F4/80. (B) Expression level of Cd11b. (C) Expression level of Cd11c. (D) Expression level of Mcp-1. (E) Expression level of Tnf-α. (F) Expression level of Leptin. Values represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.
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pone.0119784.g003: Gene expression analysis in WAT.(A) Expression level of F4/80. (B) Expression level of Cd11b. (C) Expression level of Cd11c. (D) Expression level of Mcp-1. (E) Expression level of Tnf-α. (F) Expression level of Leptin. Values represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.

Mentions: Expansion of WAT and hypertrophy of adipocytes are usually associated with adipose inflammation, and suppressing this inflammation has been shown to generate benefits in diet induced metabolic disorders [14,15]. In this context, we examined whether adipocyte hypertrophy, shown in Fig. 2, is associated with chronic inflammation. A gene expression analysis was performed on WAT and reveals that HFD progressively increased expression of macrophage marker genes, including F4/80, Cd11b and Cd11c (Fig. 3A-C). The difference reached statistical significance on week 8 and maintained until the end of the experiment (Fig. 3A-C). A similar trend was observed in Mcp-1 (Fig. 3D) and Tnf-α (Fig. 3E), two typical pro-inflammatory factors. Consistently, HFD feeding increased circulating level of TNFα (S1 Fig.). Additionally, HFD elevated leptin expression in WAT (Fig. 3F). Taken together, these data reveal that HFD progressively aggravates adipose chronic inflammation.


High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

Gao M, Ma Y, Liu D - PLoS ONE (2015)

Gene expression analysis in WAT.(A) Expression level of F4/80. (B) Expression level of Cd11b. (C) Expression level of Cd11c. (D) Expression level of Mcp-1. (E) Expression level of Tnf-α. (F) Expression level of Leptin. Values represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358885&req=5

pone.0119784.g003: Gene expression analysis in WAT.(A) Expression level of F4/80. (B) Expression level of Cd11b. (C) Expression level of Cd11c. (D) Expression level of Mcp-1. (E) Expression level of Tnf-α. (F) Expression level of Leptin. Values represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.
Mentions: Expansion of WAT and hypertrophy of adipocytes are usually associated with adipose inflammation, and suppressing this inflammation has been shown to generate benefits in diet induced metabolic disorders [14,15]. In this context, we examined whether adipocyte hypertrophy, shown in Fig. 2, is associated with chronic inflammation. A gene expression analysis was performed on WAT and reveals that HFD progressively increased expression of macrophage marker genes, including F4/80, Cd11b and Cd11c (Fig. 3A-C). The difference reached statistical significance on week 8 and maintained until the end of the experiment (Fig. 3A-C). A similar trend was observed in Mcp-1 (Fig. 3D) and Tnf-α (Fig. 3E), two typical pro-inflammatory factors. Consistently, HFD feeding increased circulating level of TNFα (S1 Fig.). Additionally, HFD elevated leptin expression in WAT (Fig. 3F). Taken together, these data reveal that HFD progressively aggravates adipose chronic inflammation.

Bottom Line: Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride.Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1.Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia, United States of America.

ABSTRACT
High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Show MeSH
Related in: MedlinePlus