Lipatrophic mice & Diabetes

Humans and animals that are lipoatrophic, lack adipose tissue, and are characterized as insulin resistant.  In order to investigate lipoatrophic diabetes, mice models are used to research this unusual association between low body fat and insulin resistance.  According to these two studies, genetically altered mice were used to investigate lipoatrophic diabetes and various treatments to correct this condition.

In a study by Gavriola et al. (2000), A-ZIP/F-1 mice, that lacked white adipose tissue (WAT), were characterized as diabetic, insulin resistant, hyperlipidemic, and reported as having enlarged organs, including the liver and pancreas.  Compared to wild-type mice, the A-ZIP/F-1 mice had serum glucose level elevated by a 2-fold difference and insulin levels elevated by a 50-fold difference.  The implantation of 900 mg of fat per mouse (about 4% body fat) was used to investigate the effects on insulin resistance.  Within 3 weeks, glucose levels returned to almost normal levels and then stabilized.  Insulin levels decreased from baseline; 53 ± 10 ng/mL to 2.1 ± 0.3 ng/mL at 8 weeks.  Insulin levels decreased by 17-35 fold and these findings suggests that the fat implantation improved insulin sensitivity.  The transplant also prevented growth of organs, including pancreatic islets and liver. Slight changes were reported with serum triglyceride levels at 3 weeks and the fat implantation was less effective with normalizing FFA and triglycerides. 

According to this study, these lipoatrophic mice corrected insulin resistance and improved serum levels of insulin, glucose, and FFA by implanting fat tissue.  This suggests that the adipose tissue is a critical factor that helps to prevent insulin resistance and diabetes.  Adipose tissue secretes regulatory hormones that control the metabolism of carbohydrates and lipids and fat implementation may be an option to treat humans.

In another study by Colomb et al. (2002), the following mice were used to investigate the relationship between leptin and lipoatrophic mice: wild type, A-ZIP/F-1 that received wild-type WAT, and A-ZIP/F-1 that received ob/ob WAT.  The specified A-ZIP/F-1 mice were implemented with 500 mg of fat; after a few weeks, leptin or saline pumps were implemented for either leptin or saline infusions.  After the fat implantation, the A-ZIP/F-1 that received wild-type WAT, improved insulin, glucose, and triglyceride levels.  Suppressed appetite and reductions in liver size and triglyceride content were found.  In contrast, the A-ZIP/F-1 that received ob/ob WAT, showed no significant improvements in glucose, insulin and triglyceride levels, and no difference in food intake, liver size, and liver content.   

After 4 weeks, infusion pumps were implanted.  Within one week, leptin levels were raised to about 5.6 ug/mL in the A-ZIP/F-1, which was slightly higher than the wild-type controls.  It was found that leptin infusions dramatically reduced insulin levels and decreased glucose levels but at a slower rate.  No significant differences were found among the mice that were treated with only leptin and leptin plus ob/ob WAT transplant. 

This study suggests that leptin and adipose tissue implantation shows major effects on insulin sensitivity and blood lipid content.