Kupffer cells are not responsible for splanchnic sequestration of amino acids in old rats

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Background: In the postprandial state, splanchnic extraction of leucine is two-fold higher in elderly humans and in old rats compared with adults. This splanchnic sequestration of Leu (SSLeu) reduces the peripheral availability of dietary Leu, which is a key player in the regulation of muscle protein synthesis. Thus, SSLeu could contribute to sarcopenia, which is a major public health issue. However, the underlying mechanism of SSLeu remains totally unknown. Our working hypothesis is that the low-grade inflammation occurring during aging could lead to Kupffer cell (KC) activation in the liver which, in turn, could lead to SSLeu and the subsequent decrease in peripheral Leu availability. Methods: 24-month old rats received an i.v. injection of either GdCl3 (to destroy KC) or saline (control group). 24 hours later, the anesthetized animals underwent surgery and were studied in fed state. A primed continuous infusion of 1-13C-Leucine was administered in the jugular vein. Nutrition and 2H3-Leucine were continuously infused into the duodenum (id) during 60 min. Blood samples were then collected from the carotid artery. Splanchnic extraction (SPE) = [1 − (Ra 2H3-Leu / Ra 13C-Leu)] x100 where Ra = rate of appearance. Results: Conclusions: In old rats, the age-related activation of KC is not directly responsible for SSLeu. Indeed, invalidation of KC was unable to normalize SSLeu to what the value observed in adult rats (SPE = 25%). To our knowledge, this is the first mechanistic study in the field, and it enables an important hypothesis to be ruled out.