Wie Fasten den Erfolg einer Operation beeinflussen kann
Dietary protein content controls lipid metabolism independent of total calorie intake
Our research has been focused on understanding the nutritional and molecular basis underlying the ability of short-term dietary interventions, including water-only fasting or reduced food intake (dietary restriction, DR), to increase stress resistance in pre-clinical models of surgical stress. For example, we have found that 3 days of fasting or 1 week of 50% DR in rodents protects against common surgical complications such as ischemia reperfusion injury to various organs (brain, kidney and liver) or intimal hyperplasia, with important translational implications for what we should (or shouldn’t) eat prior to surgery. In both cases, removal of dietary protein could largely recapitulate the effects of fasting or DR on surgical stress resistance. However, protein restriction also induced beneficial changes in glucose and lipid metabolism, including improved insulin sensitivity and blood lipid profiles.
Here, we propose a model in which dietary protein content is the major determinant of whether fat is stored in white adipose tissue (WAT), or mobilized from WAT to liver for redistribution and oxidation. Our data indicate that rodents fed for 1 week on a diet lacking protein display fasting-like changes including loss of body weight, reduced adiposity, increased fatty acid oxidation, and reduced circulating triglycerides (TG). Importantly, these changes occurred independent of total calorie intake on diets that were high either in sugar content (90% of calories, with 50% from sucrose) or fat content (60% of calories). Genetic studies revealed that hyperactivation of the nutrient/energy sensing kinase mTORC1 specifically in the liver blocked the improvement in circulating TG on a protein free diet, prompting us to look in greater depth in the liver for underlying molecular mechanisms. We found that protein restriction altered the fate of fatty acids entering the liver from the WAT by both reducing secretion of VLDL particles and promoting lipid droplet formation and fatty acid oxidation. Finally, we identified a liver-specific transcription factor that controls this switch, and a novel mechanism by which dietary protein restriction results in its activation. Taken together, our data suggest that modulation of dietary protein intake is a powerful and rapid trigger of beneficial changes in both stress resistance and energy metabolism.
Prof. James Mitchell, Boston (USA)
Forschungslabor der Abteilung of Genetics and Complex Diseases an der Harvard University School of Public Health.
Sein Hauptforschungsgebiet betrifft den besonderen Widerstand, den Zellen und Organismen während eines Fastens entwickeln.