title: All-trans retinoic acid modifies the expression of clock and disease marker genes.
abstract: Restricted feeding (RF), a regimen that restricts the duration of food availability with no calorie restriction, entrains the circadian clock in peripheral tissues. Restricted feeding leads to high-amplitude circadian rhythms, which have been shown to promote wellness and reduce disease and inflammatory markers. Retinoids, such as all-trans retinoic acid (ATRA), act as anti-inflammatory agents. Thus far, the effect of ATRA combined with RF on the ability to delay the occurrence of age-associated changes, such as cancer and inflammation, is not known. We measured circadian expression of clock genes, disease marker genes and inflammatory markers in the serum, liver and jejunum in mice fed ad libitum (AL) or RF supplemented with 15 or 250 μg/kg body/day ATRA for 16 weeks. Our results show that ATRA supplementation led to phase shifts and reduced amplitudes in clock genes. Under AL, ATRA reduced the average daily messenger RNA (mRNA) levels of some disease markers, such as liver Afp and jejunum Afp, Alt and Gadd45β and aspartate transaminase (AST) protein in the serum, but increased the expression level of liver Crp mRNA. Under RF, ATRA reduced the average daily levels of jejunum Alt and Gadd45β and AST protein in the serum, but increased liver Afp, Alt, Gadd45β and Arginase mRNA. Altogether, our findings suggest that ATRA strongly affects circadian oscillation and disease marker levels. Moreover, its impact is different depending on the feeding regimen (AL or RF).
authors.affiliation: Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Sherman
authors.forename: Roee
authors.initials: R
authors.lastname: Gutman
authors.forename: Nava
authors.initials: N
authors.lastname: Chapnik
authors.forename: Jenny
authors.initials: J
authors.lastname: Meylan
authors.forename: Johannes
authors.initials: J
authors.lastname: le Coutre
authors.forename: Oren
authors.initials: O
authors.lastname: Froy
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation / Q000097:blood / Q000235:genetics / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D031204:Caloric Restriction; D057906:Circadian Clocks; D002940:Circadian Rhythm; D005786:Gene Expression Regulation; D005819:Genetic Markers; D007583:Jejunum / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; D001219:Aspartate Aminotransferases; D002097:C-Reactive Protein; D056926:CLOCK Proteins; D005819:Genetic Markers; D012333:RNA, Messenger; D014157:Transcription Factors; D014212:Tretinoin; D000509:alpha-Fetoproteins; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C545206:alpha-fetoprotein related protein, mouse