High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice - PubMed (original) (raw)

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

Mingming Gao et al. PLoS One. 2015.

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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. HFD increased body weight gain in female CD-1 mice.

(A) Growth curve of mice on HFD or chow. (B) Representative images of mice (bar length = 1 cm). (C) Energy intake. Values in (A) and (C) represent average ± SD (n = 10). * P < 0.05 compared with mice on chow, ** P < 0.01 compared with mice on chow.

Fig 2. 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.

Fig 3. 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.

Fig 4. 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.

Fig 5. HFD induced hepatic steatosis.

(A) Representative images of liver histological examinations. (B) Liver triglyceride determination. (C) Blood aspartate aminotransferase. (D) Blood alanine aminotransferase. Values in (B), (C) and (D) represent average ± SD (n = 4). ** P < 0.01 compared with mice on chow.

Fig 6. Gene expression in liver.

(A) Expression level of Ppar-γ2. (B) Expression level of Cd36. (C) Expression level of Mgat1. (D) Expression level of Fgf21. Values represent average ± SD (n = 4). * P < 0.05 compared with mice on chow, ** P < 0.01 compared with mice on chow.

Fig 7. 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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High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice - PubMed (original) (raw)