title: Involvement of adenosine monophosphate-activated protein kinase in the influence of timed high-fat evening diet on the hepatic clock and lipogenic gene expression in mice.
abstract: A high-fat diet may result in changes in hepatic clock gene expression, but potential mechanisms are not yet elucidated. Adenosine monophosphate-activated protein kinase (AMPK) is a serine/threonine protein kinase that is recognized as a key regulator of energy metabolism and certain clock genes. Therefore, we hypothesized that AMPK may be involved in the alteration of hepatic clock gene expression under a high-fat environment. This study aimed to examine the effects of timed high-fat evening diet on the activity of hepatic AMPK, clock genes, and lipogenic genes. Mice with hyperlipidemic fatty livers were induced by orally administering high-fat milk via gavage every evening (19:00-20:00) for 6 weeks. Results showed that timed high-fat diet in the evening not only decreased the hepatic AMPK protein expression and activity but also disturbed its circadian rhythm. Accordingly, the hepatic clock genes, including clock, brain-muscle-Arnt-like 1, cryptochrome 2, and period 2, exhibited prominent changes in their expression rhythms and/or amplitudes. The diurnal rhythms of the messenger RNA expression of peroxisome proliferator-activated receptorα, acetyl-CoA carboxylase 1α, and carnitine palmitoyltransferase 1 were also disrupted; the amplitude of peroxisome proliferator-activated receptorγcoactivator 1α was significantly decreased at 3 time points, and fatty liver was observed. These findings demonstrate that timed high-fat diet at night can change hepatic AMPK protein levels, activity, and circadian rhythm, which may subsequently alter the circadian expression of several hepatic clock genes and finally result in the disorder of hepatic lipogenic gene expression and the formation of fatty liver.
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China; Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China; Department of Pharmacy, The Affiliated Children's Hospital of Soochow University, Suzhou 215003, Jiangsu Province, China.
authors.forename: Zengyan
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Pharmacology, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu Province, China. Electronic address: xuejie@suda.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Xue
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005247:Feeding Behavior; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation; D050155:Lipogenesis / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D047493:PPAR alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D047493:PPAR alpha; D012333:RNA, Messenger; D000249:Adenosine Monophosphate; D002334:Carnitine O-Palmitoyltransferase; D056926:CLOCK Proteins; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase
keywords: Adenosine monophosphate–activated protein kinase; Clock genes; Fatty liver; High-fat diet; Lipogenic genes; Peroxisome proliferator–activated receptor α