Removal of Visceral Fat Improves Metabolic Syndrome and Hepatic Steatosis in Diet-Induced Obese Mice
Xavier Dray*1, Zhiping Li1, Jing Hua1, Samuel a. Giday1, Susan K. Redding2, Eun Ji Shin1, Ron J. Wroblewski1, Jonathan M. Buscaglia1, Priscilla Magno1, Dawn Ruben2, Michael a. Schweitzer4, Jeanne Clark3, Anthony N. Kalloo1
1Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD; 2Radiology Research Service Centre, Johns Hopkins School of Medicine, Baltimore, MD; 3Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD; 4Department of Surgery, Johns Hopkins Bayview Medical Center, Baltimore, MD
Background: Increased visceral adiposity is a common feature of obesity and metabolic syndrome. The amount of visceral fat (VF) correlates with the insulin sensitivity, the key component of metabolic syndrome. We evaluated the effect of VF removal by laparotomy in a mouse model of diet-induced obesity and metabolic syndrome.
Methods: Wild type C57BL6 male mice were fed either a high fat diet (HFD, n=14) or a normal diet (ND, n=6) for 8 weeks. HFD mice were assigned to surgical removal of VF (HFD+VF-) or to sham surgery (HFD+VF+). The mice were fed additional 4 weeks on the same diet. Body weight, glucose tolerance,serum adipokines (ELISA), hepatic cytokine expressions (quantitative PCR) and liver histology were evaluated at the end of the 12 week study period.
Results: HFD induced obesity, insulin resistance and hepatic steatosis. A mean of 2.1±0.4 g (4.9±0.5% of body weight) VF was removed in HFD+VF- mice. Both HFD+VF- and HFD+VF+ mice recovered equally well from surgery and consumed similar amount of diet post operation. However, HFD+VF- mice lost more weight and had significant improvement in insulin sensitivity and hepatic steatosis. HFD+VF- mice also had significant lower serum leptin level, but a similar adiponectin level compared to controls, and had lower expression of hepatic TNFα.
Conclusion: Surgical VF removal improves insulin resistance and hepatic steatosis in mice with diet-induced metabolic syndrome and improves adipokine and cytokine profiles. VF removal may be a useful tool to treat metabolic syndrome in obesity.
| Week 12 | ND | HFD+VF+ | HFD+VF- |
| Weight (g) | 24.0±1.8 | 47.6±0.1* | 37.0±3.8** |
| Steatosis grade | 0.0±0.0 | 2.8±0.4 * | 0.3±0.5** |
| Leptin (ng/mL) | 8.3±4.5 | 56.3±2.5* | 40.5±6.1* |
| TNFα/GAPDH | 0.2±0.1 | 2.2±0.8 | 1.1±0.4** |
* p<0.05 compared to ND; ** p<0.05 compared to HFD
