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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 whitening of BAT without significantly changing blood clearance of triglyceride.(A) Representative images of BAT histological examinations. (B) Measurement of BAT nuclei. (C) Determination of Blood triglyceride. (D) Representative image of lipoprotein electrophoresis (C for chow and H for HFD). Values in (B) and (C) represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.
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pone.0119784.g004: HFD caused whitening of BAT without significantly changing blood clearance of triglyceride.(A) Representative images of BAT histological examinations. (B) Measurement of BAT nuclei. (C) Determination of Blood triglyceride. (D) Representative image of lipoprotein electrophoresis (C for chow and H for HFD). Values in (B) and (C) represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.

Mentions: BAT is a highly vascularized tissue specialized in maintaining body temperature by consuming lipid and glucose. Recent studies demonstrate that BAT plays important roles in regulating glucose and triglyceride metabolism [16,17]. In this context, we questioned whether HFD altered BAT morphology and subsequently affected blood triglyceride clearance. Fig. 4A shows that HFD progressively induced fat deposition in BAT, resulting in expansion and whitening of this tissue. This is further confirmed by quantitative determination showing that the average amount of nuclei per 104 μm2 was greatly reduced by ∼57% at the end of the experiment (Fig. 4B). Neither blood triglyceride nor lipoprotein profiles were significantly altered by HFD feeding (Fig. 4C-D). No significant difference in free fatty acids in blood was identified between mice on HFD and those on regular chow (S2 Fig.). Overall, this set of results proves that HFD induces whitening of BAT without significantly changing blood concentrations of triglyceride and free fatty acids.


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 whitening of BAT without significantly changing blood clearance of triglyceride.(A) Representative images of BAT histological examinations. (B) Measurement of BAT nuclei. (C) Determination of Blood triglyceride. (D) Representative image of lipoprotein electrophoresis (C for chow and H for HFD). Values in (B) and (C) represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0119784.g004: HFD caused whitening of BAT without significantly changing blood clearance of triglyceride.(A) Representative images of BAT histological examinations. (B) Measurement of BAT nuclei. (C) Determination of Blood triglyceride. (D) Representative image of lipoprotein electrophoresis (C for chow and H for HFD). Values in (B) and (C) represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.
Mentions: BAT is a highly vascularized tissue specialized in maintaining body temperature by consuming lipid and glucose. Recent studies demonstrate that BAT plays important roles in regulating glucose and triglyceride metabolism [16,17]. In this context, we questioned whether HFD altered BAT morphology and subsequently affected blood triglyceride clearance. Fig. 4A shows that HFD progressively induced fat deposition in BAT, resulting in expansion and whitening of this tissue. This is further confirmed by quantitative determination showing that the average amount of nuclei per 104 μm2 was greatly reduced by ∼57% at the end of the experiment (Fig. 4B). Neither blood triglyceride nor lipoprotein profiles were significantly altered by HFD feeding (Fig. 4C-D). No significant difference in free fatty acids in blood was identified between mice on HFD and those on regular chow (S2 Fig.). Overall, this set of results proves that HFD induces whitening of BAT without significantly changing blood concentrations of triglyceride and free fatty acids.

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