Resistance to obesity in Lou/C rats prevents ageing-associated metabolic alterations

Ageing is associated with metabolic alterations characterised by changes in energy expenditure, obesity, leptin and insulin resistance. The Lou/C rat, an inbred strain of Wistar origin, is presented as both an obesity-resistant rat and a model of healthy ageing.

To characterise the mechanisms underlying obesity resistance in Lou/C rat, we measured food intake and energy expenditure by indirect calorimetry at 1, 6, 12, 18, and 24 months of age. Moreover, plasma insulin and leptin concentrations were assessed by radioimmunoassay in Lou/C and Wistar rats throughout their life span.

Compared to Wistar rats, Lou/C rats presented a higher food intake only at 24 months of age and they had a higher energy expenditure at 6 and 12 months of age (+21% and +14%, respectively). Plasma insulin concentration increased markedly in 18- and 24-month-old Wistar rats, but remained stable during ageing in Lou/C rats. From the age of 6 months, the plasma leptin concentrations in Wistar rats were higher than in Lou/C rats of the same age (four-, seven-, five- and threefold higher at 6, 12, 18, 24 months of age, respectively).

Compared to Wistar rats, Lou/C rats did not develop insulin resistance as confirmed by a higher glucose infusion rate during the hyperinsulinaemic-euglycaemic clamp. These data provide evidence that insulin resistance is associated with the excess of adipose tissue in Wistar rats. Not only Lou/C rats present a higher median life span than Wistar rats (+20%), but they also show a healthy ageing process considering fat accretion and insulin resistance.