title: Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.
abstract: Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.
authors.affiliation: 1 Institute of Human Nutrition and Food Science, University of Kiel , Kiel, Germany .
authors.forename: Anke
authors.initials: A
authors.lastname: Schloesser
authors.forename: Graeme
authors.initials: G
authors.lastname: Campbell
authors.forename: Claus-Christian
authors.initials: CC
authors.lastname: Glüer
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: Patricia
authors.initials: P
authors.lastname: Huebbe
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001823:Body Composition; D002151:Calorimetry; D016922:Cellular Senescence; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D004041:Dietary Fats; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D005943:Gluconeogenesis; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000737:chemistry; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D008055:Lipids; D011506:Proteins; C035737:major urinary proteins; D002784:Cholesterol; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D010100:Oxygen