Mammals and birds adapt to prolonged fasting by mobilizing fat stores and minimizing protein loss. This strategy ends with an increase in protein utilization associated with behavioural changes promoting food foraging. Using the Zucker rat as a model, we have investigated the effect of severe obesity on this pattern of protein loss during long-term fasting. Two interactions between the initial adiposity and protein utilization were found. First, protein conservation was more effective in obese than in lean rats: fatty rats had a three times lower daily nitrogen excretion and proportion of energy expenditure deriving from proteins, and a lower daily protein loss in various muscles. This phase of protein sparing is moreover nine times longer in the fatty rats. Second, obese animals did not show the late increase in nitrogen excretion that occurred in their lean littermates. Total body protein loss during starvation was larger in fatty rats (57% versus 29%) and, accordingly, total protein loss was greater in their muscles. At the end of the experiment, lean and obese rats had lost 98% and 82%, respectively, of their initial lipid reserves, and fatty rats still had an obese body composition. These results support the hypothesis that in severely obese humans and animals a lethal cumulative protein loss is reached long before the exhaustion of fat stores, while the phase of protein conservation is still continuing. In contrast, in lean rats, survival of fasting seems to depend on the availability of lipid fuels.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE:To examine the possible involvement of an increase in diet-induced thermogenesis from brown adipose tissue (BAT) in the n-3 polyunsaturated fatty acids (n-3 PUFA) induced limitation of the development of white fat pads during high-fat feeding. DESIGN: Rats fed for four weeks on a low-fat/high-carbohydrate diet (C group) or high-fat diet without n-3 PUFA (REF group), with eicosapentaenoic acid (EPA group), with docosahexaenoic acid (DHA group) or with a mixture of these two fatty acids (MIX group). MEASUREMENTS: Epididymal and retroperitoneal fat pad mass, BAT composition, Guanosine 5'-diphosphate (GDP) binding and uncoupling protein (UCP) content were measured in the ®ve groups of rats. RESULTS: The masses of retroperitoneal and epididymal white fat pads were lower in the groups fed n-3 PUFA than in the C and REF groups. The total BAT GDP binding was 1.6 times higher in the MIX and EPA groups than in the REF group. The BAT from the EPA group presented an enrichment in mitochondria compared to the C and REF groups whereas the BAT from the DHA and REF groups presented a hyperplasia and an increase in thermogenic activity of the mitochondria compared to the C group. The higher thermogenic activity of BAT was observed in the MIX group and is due to hyperplasia and to an increase in thermogenic activity of mitochondria. CONCLUSIONS: n-3 PUFA induce a marked stimulation of BAT thermogenic activity without changes in the UCP content compared to a high-fat diet without n-3 PUFA. The mixture of EPA and DHA has the more pronounced effect while EPA and DHA seem to act in synergy on BAT thermogenesis via different mechanisms.

Melatonin, an important marker of the endogenous rhythmicity in mammals, also plays a role in the body defence against pathogens and injuries. In vitro experiments have shown that either pro- or anti-inflammatory agents, acting directly in the organ, are able to change noradrenaline-induced pineal indoleamine production. Whereas corticosterone potentiates melatonin production, incubation of the gland with tumour necrosis factor-alpha decreases pineal hormonal production. In the present study, we show that nocturnal melatonin production measured by intra-pineal microdialysis is enhanced in pineals perfused with corticosterone at concentrations similar to those measured in inflamed animals. In vitro experiments suggest that this enhancement may be due to an increase in the activity of the two enzymes that convert serotonin to N-acetylserotonin (NAS) and NAS to melatonin. The present results support the hypothesis that the pineal gland is a sensor of inflammation mediators and that it plays a central role in the control of the inflammatory response.

Photoperiodic changes of pineal melatonin (MEL) profile are accompanied by parallel changes of arylalkylamine-N-acetyltransferase (AA-NAT) activity. In the present study, the authors investigated, for the first time, whether two other important variables of pineal metabolism, AA-NAT and hydroxyindole-O-methyltransferase (HIOMT) gene expression, also may be affected by the photoperiod. Evening rises in AA-NAT and HIOMT mRNA and in circulating MEL occurred concomitantly with an increased delay from dark onset as scotophase shortened. On the opposite, the morning declines of all three variables occurred with different kinetics but were locked to light onset. These observations demonstrate that the daily rhythms in AA-NAT and HIOMT gene expression are modulated by the photoperiod and bring further evidence in favor of nor adrenaline as the possible link between the endogenous clock and MEL. Interestingly, the duration of the nocturnal peak in HIOMT mRNA was positively correlated with HIOMT activity. In conclusion, this study adds two important links to the chain of mechanisms involved in the photoperiodic control of pineal metabolism. First, photoperiodic modulation of the MEL rhythm primarily results from changes in the AA-NAT gene expression. Second, the photoperiodic regulation of HIOMT activity occurs at the transcriptional level.