Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance.

Lipoprotein lipase (LPL) plays a rate-limiting role in triglyceride-rich lipoprotein metabolism and is expressed in most tissues. Overexpression of LPL in skeletal muscle has been linked with higher plasma glucose levels suggesting insulin resistance (Jensen et al., Am J Physiol 273:R683-R689, 1997). The aim of our study was to ascertain whether the overexpression of human LPL in skeletal muscle leads to insulin resistance and to investigate the mechanism. Respiratory quotient measurements in both transgenic (MCKhLPL) and nontransgenic mice on a high-carbohydrate diet were conducted and showed a shift in fuel usage in transgenic mice when fasting but not when actively feeding. An increase in citrate and glucose 6-phosphate levels in fasted MCKhLPL mice further supports this preferential use of lipids. When challenged with an intraperitoneal injection of glucose (1 g/kg), MCKhLPL mice had a higher plasma glycemic excursion than nontransgenic mice. No differences in insulin response were observed between the two groups. Further investigation using hyperinsulinemic-euglycemic clamps revealed insulin resistance in MCKhLPL mice. Despite signs of insulin resistance, there was no associated increase in free fatty acids, hypertriglyceridemia, or hyperinsulinemia in MCKhLPL mice. In conclusion, MCKhLPL mice are insulin resistant, presumably due to increased delivery of lipoprotein-derived fatty acids to muscle.

The effects of caloric restriction on the body composition and hibernation of the golden-mantled ground squirrel (Spermophilus lateralis).

In preparation for hibernation, golden-mantled ground squirrels (Spermophilus lateralis) must deposit sufficient amounts of lipid during the summer to survive winter hibernation. We conducted an experiment from May 1998 to February 1999 to examine the effects of caloric restriction on the body composition (lipid and fat-free mass) and hibernation of golden-mantled ground squirrels. Ground squirrels were either provided with food ad lib. (controls) or with only enough food to maintain a constant body mass throughout the experiment (calorically restricted). Changes in body composition were followed using total body electrical conductivity (TOBEC). Implanted data loggers that recorded body temperature were used to determine when ground squirrels entered their first torpor bout and the lengths of torpor bouts. Body composition did not change in the calorically restricted ground squirrels between May and September, while both lipid and fat-free mass increased in the controls. However, from September to February, calorically restricted ground squirrels lost only fat-free mass, not lipid mass, but controls lost both lipid and fat-free mass. Calorically restricted ground squirrels entered their first torpor bout about 4 wk after controls, but the torpor bout duration (or length) during hibernation did not differ between the two groups. These results show that ground squirrels maintain body composition during caloric restriction, and the limited quantities of stored lipid have an effect on when hibernation begins but not on torpor bout length.