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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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HFD caused hypertrophy of white adipocytes.(A) Lean mass (n = 10). (B) Fat mass (n = 10). (C) Representative images of WAT histological examinations (bar length = 100 μm). (D) Adipocyte diameter (n = 4). Values in (A), (B) and (D) represent average ± SD. ** P < 0.01 compared with mice on chow.
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pone.0119784.g002: HFD caused hypertrophy of white adipocytes.(A) Lean mass (n = 10). (B) Fat mass (n = 10). (C) Representative images of WAT histological examinations (bar length = 100 μm). (D) Adipocyte diameter (n = 4). Values in (A), (B) and (D) represent average ± SD. ** P < 0.01 compared with mice on chow.

Mentions: Next, we questioned whether the accelerated body weight gain is derived from lean mass or fat mass or a combination. To answer this, we measured their body composition monthly using magnetic resonance imaging. Although no significant difference in lean mass was observed (Fig. 2A), mice on the HFD gradually gained more fat mass compared to those on chow (Fig. 2B). At the end of the experiment, the average fat mass was ∼3.6 g and ∼12.7 g for mice on chow or HFD, respectively (Fig. 2B). Histologic examination of WAT demonstrates that HFD progressively increased the size of adipocytes and induced a significant level of adipocyte hypertrophy at the end of the experiment (Fig. 2C). This trend is further confirmed by quantitative determination of adipocyte diameter using an image system showing that the average diameter was ∼110 μm for mice on an HFD while that on chow was merely ∼40 μm (Fig. 2C). Collectively, these data demonstrate that an HFD greatly increases fat mass in female CD-1 mice, which is associated adipocyte hypertrophy.


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)

HFD caused hypertrophy of white adipocytes.(A) Lean mass (n = 10). (B) Fat mass (n = 10). (C) Representative images of WAT histological examinations (bar length = 100 μm). (D) Adipocyte diameter (n = 4). Values in (A), (B) and (D) represent average ± SD. ** 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.g002: HFD caused hypertrophy of white adipocytes.(A) Lean mass (n = 10). (B) Fat mass (n = 10). (C) Representative images of WAT histological examinations (bar length = 100 μm). (D) Adipocyte diameter (n = 4). Values in (A), (B) and (D) represent average ± SD. ** P < 0.01 compared with mice on chow.
Mentions: Next, we questioned whether the accelerated body weight gain is derived from lean mass or fat mass or a combination. To answer this, we measured their body composition monthly using magnetic resonance imaging. Although no significant difference in lean mass was observed (Fig. 2A), mice on the HFD gradually gained more fat mass compared to those on chow (Fig. 2B). At the end of the experiment, the average fat mass was ∼3.6 g and ∼12.7 g for mice on chow or HFD, respectively (Fig. 2B). Histologic examination of WAT demonstrates that HFD progressively increased the size of adipocytes and induced a significant level of adipocyte hypertrophy at the end of the experiment (Fig. 2C). This trend is further confirmed by quantitative determination of adipocyte diameter using an image system showing that the average diameter was ∼110 μm for mice on an HFD while that on chow was merely ∼40 μm (Fig. 2C). Collectively, these data demonstrate that an HFD greatly increases fat mass in female CD-1 mice, which is associated adipocyte hypertrophy.

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