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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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Related in: MedlinePlus

HFD impaired glucose homeostasis, which subsequently gave rise to hyperinsulinemia and pancreatic islet hypertrophy.(A) Profiles of blood glucose concentration as function of time upon intraperitoneal injection of glucose (n = 5). (B) Profiles of glucose concentration (percentage of initial value) as a function of time upon intraperitoneal injection of insulin (n = 5). (C) Blood insulin (n = 4). (D) Representative images of pancreas histological examinations. Values in (A), (B) and (C) represent average ± SD. * P < 0.05 compared with mice on chow, ** P < 0.01 compared with mice on chow.
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pone.0119784.g007: HFD impaired glucose homeostasis, which subsequently gave rise to hyperinsulinemia and pancreatic islet hypertrophy.(A) Profiles of blood glucose concentration as function of time upon intraperitoneal injection of glucose (n = 5). (B) Profiles of glucose concentration (percentage of initial value) as a function of time upon intraperitoneal injection of insulin (n = 5). (C) Blood insulin (n = 4). (D) Representative images of pancreas histological examinations. Values in (A), (B) and (C) represent average ± SD. * P < 0.05 compared with mice on chow, ** P < 0.01 compared with mice on chow.

Mentions: Adipose inflammation and ectopic lipid deposition are key factors contributing to impaired glucose metabolism in obesity. To investigate whether HFD negatively affects glucose homeostasis in female CD-1 mice, we conducted IPGTT and ITT. Fig. 7A shows that compared with mice on chow, HFD-fed mice exhibited reduced glucose tolerance. This impaired glucose homeostasis results primarily from insulin resistance, as evidenced by the reduced sensitivity to insulin administration in ITT (Fig. 7B). HFD progressively elevated blood insulin, giving rise to a significant level of hyperinsulinemia at the end of the experiment (Fig. 7C). The elevated blood insulin was associated with gradually exacerbated pancreatic islet hypertrophy (Fig. 7D). Taken together, these data prove that HFD impairs glucose homeostasis via inducing insulin resistance, which consequently gives rise to hyperinsulinemia and pancreatic islet 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 impaired glucose homeostasis, which subsequently gave rise to hyperinsulinemia and pancreatic islet hypertrophy.(A) Profiles of blood glucose concentration as function of time upon intraperitoneal injection of glucose (n = 5). (B) Profiles of glucose concentration (percentage of initial value) as a function of time upon intraperitoneal injection of insulin (n = 5). (C) Blood insulin (n = 4). (D) Representative images of pancreas histological examinations. Values in (A), (B) and (C) represent average ± SD. * P < 0.05 compared with mice on chow, ** 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.g007: HFD impaired glucose homeostasis, which subsequently gave rise to hyperinsulinemia and pancreatic islet hypertrophy.(A) Profiles of blood glucose concentration as function of time upon intraperitoneal injection of glucose (n = 5). (B) Profiles of glucose concentration (percentage of initial value) as a function of time upon intraperitoneal injection of insulin (n = 5). (C) Blood insulin (n = 4). (D) Representative images of pancreas histological examinations. Values in (A), (B) and (C) represent average ± SD. * P < 0.05 compared with mice on chow, ** P < 0.01 compared with mice on chow.
Mentions: Adipose inflammation and ectopic lipid deposition are key factors contributing to impaired glucose metabolism in obesity. To investigate whether HFD negatively affects glucose homeostasis in female CD-1 mice, we conducted IPGTT and ITT. Fig. 7A shows that compared with mice on chow, HFD-fed mice exhibited reduced glucose tolerance. This impaired glucose homeostasis results primarily from insulin resistance, as evidenced by the reduced sensitivity to insulin administration in ITT (Fig. 7B). HFD progressively elevated blood insulin, giving rise to a significant level of hyperinsulinemia at the end of the experiment (Fig. 7C). The elevated blood insulin was associated with gradually exacerbated pancreatic islet hypertrophy (Fig. 7D). Taken together, these data prove that HFD impairs glucose homeostasis via inducing insulin resistance, which consequently gives rise to hyperinsulinemia and pancreatic islet 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