The LIRKO mouse has no insulin receptors in its liver. It's one pretty sickly mouse. In most studies it becomes hyperglycemic and hyperinsulinemic very early in life, but by six months or so of age is either normoglycemic or hypoglycemic. Despite the concurrent hyperglycemia and hyperinsulinemia, the LIRKO remains normal weight, it is even a bit underweight if anything. This is despite the fact that circulating free fatty acids (FFA, or my preferred acronym, NEFA) are suppressed by 40%. {Here are the two papers I've discussed in previous blog posts: Loss of Insulin Signaling in Hepatocytes Leads to Severe Insulin Resistance and Progressive Hepatic Dysfunction , High Circulating Leptin Receptors with Normal Leptin Sensitivity in Liver-specific Insulin Receptor Knock-out (LIRKO) Mice both links are to free full texts}
LIRKO presents two problems for the TWICHOOB:
1. Chronic hyperinsulinemia does not cause rampant fat accumulation
2. Insulin "locking away" fats does not lead to hyperphagia (overeating)
