title: Changes in the daily rhythm of lipid metabolism in the diabetic retina.
abstract: Disruption of circadian regulation was recently shown to cause diabetes and metabolic disease. We have previously demonstrated that retinal lipid metabolism contributed to the development of diabetic retinopathy. The goal of this study was to determine the effect of diabetes on circadian regulation of clock genes and lipid metabolism genes in the retina and retinal endothelial cells (REC). Diabetes had a pronounced inhibitory effect on the negative clock arm with lower amplitude of the period (per) 1 in the retina; lower amplitude and a phase shift of per2 in the liver; and a loss of cryptochrome (cry) 2 rhythmic pattern in suprachiasmatic nucleus (SCN). The positive clock arm was increased by diabetes with higher amplitude of circadian locomotor output cycles kaput (CLOCK) and brain and muscle aryl-hydrocarbon receptor nuclear translocator-like 1 (bmal1) and phase shift in bmal1 rhythmic oscillations in the retina; and higher bmal1 amplitude in the SCN. Peroxisome proliferator-activated receptor (PPAR) α exhibited rhythmic oscillation in retina and liver; PPARγ had lower amplitude in diabetic liver; sterol regulatory element-binding protein (srebp) 1c had higher amplitude in the retina but lower in the liver in STZ- induced diabetic animals. Both of Elongase (Elovl) 2 and Elovl4 had a rhythmic oscillation pattern in the control retina. Diabetic retinas lost Elovl4 rhythmic oscillation and had lower amplitude of Elovl2 oscillations. In line with the in vivo data, circadian expression levels of CLOCK, bmal1 and srebp1c had higher amplitude in rat REC (rREC) isolated from diabetic rats compared with control rats, while PPARγ and Elovl2 had lower amplitude in diabetic rREC. In conclusion, diabetes causes dysregulation of circadian expression of clock genes and the genes controlling lipid metabolism in the retina with potential implications for the development of diabetic retinopathy.
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Tikhonenko
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Bozack
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Lydic
authors.affiliation: Department of Psychology Social Science, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Lily
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Panchy
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McSorley
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Faber
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Ophthalmology, Indiana University, Indianapolis, Indiana, United States of America.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Boulton
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
authors.affiliation: Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America.
authors.forename: Julia V
authors.initials: JV
authors.lastname: Busik
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012160:Retina / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D056926:CLOCK Proteins
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