Kontrolle des Energiestoffwechsels im Säuglingsalter: Vergleich genetisch fettsüchtiger und normaler Ratten

Abstract

The defective gene "fa" results in a syndrome that includes excessive body fat deposition, hyperglycemia and hyperinsulinemia. The first aim of this study was to systematically analyse the earliest disturbances in energy deposition of fa/fa rats. The second aim was to determine the influence of the sympathetic nervous system on the development of these disturbances.

Animals used in this study were the offspring of Zucker rat x Brown Norway rat hybrid matings. The genotype of these animals could already be identified during the perinatal period using established polymerase chain reaction (PCR) techniques to detect differences in known marker genes which are located less than 2 cM from the fa gene.

Whole body composition analysis of 0- to 16-day-old pups demonstrated that body fat of fa/fa animals does not significantly exceed that of +/fa animals before 7 days of age. By 16 days of age the body fat content of fa/fa hybrids as well as of fa/fa Zucker rats was so much higher than that of their +/fa littermates that their genotype could be identified by the relationship between body fat and body mass. At this age the fat free dry mass (ffTM) of fa/fa pups was slightly higher that that of their +/fa littermates. There was no genotype difference in body water mass. The higher fat mass together with a slightly higher ffTM of fa/fa animals resulted in a significant effect of the genotype on body mass.

Triglyceride content in brown adipose tissue, white adipose tissue, liver and plasma of 1-day-old fa/fa pups was not different from that of their lean littermates. Moreover, there could be found neither genotype differences in liver glycogen, the crucial perinatal energy store, nor in the plasma insulin of fetuses and newborn animals.

The importance of the decreased sympathetic tone for the development of the fa/fa adipositas was tested by chronical oral treatment of 4- to 16-day-old, artificially reared animals with Noradrenalin (NA). This treatment increased the total metabolic rate of both genotypes to the same extent while the mass specific metabolic rate was elevated 120 % above the thermoneutral level. Moreover the fat deposition of both genotypes was equalized at low values. In contrast, the treatment induced no genotype-specific reduction of the fat free dry mass. The reduced growth of fa/fa animals during the 2nd week of life was a consequence of their body water content decreasing compared to that of their +/fa littermates. Furthermore the development of genotype differences in plasma insulin levels and plasma triglycerides could be eliminated by NA treatment. These results indicate that decreased sympathetic outflow is of crucial importance for the development of the earliest stages of the fa/fa adipositas.