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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 receptor α , acetyl-CoA carboxylase 1 α , and carnitine palmitoyltransferase 1 were also disrupted; the amplitude of peroxisome proliferator–activated receptor γ coactivator 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. [ABSTRACT FROM AUTHOR]

Luteolin, a natural flavonoid, can attenuate hepatic lipid accumulation and insulin resistance in obese mice. Therefore, we hypothesized that luteolin may also improve the abnormal glucolipid metabolism of hypertrophic myocardial cells. This study aimed to investigate the effect and possible molecular mechanisms of luteolin. Hypertrophic H9c2 cells were induced by angiotensin II/hypoxia and simultaneously treated with 2 to 8 μg/mL luteolin for 24 h. Luteolin might dose-dependently decrease intracellular total protein, atrial natriuretic peptide, and free fatty acid levels, and increase supernatant glucose levels. Western blot assay showed that luteolin could inhibit the expressions of intracellular hypoxia inducible factor-1α (HIF-1α) and glucose transporter-4 (GLUT-4) proteins, and increase the expressions of intracellular peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1A (CPT-1A), and pyruvate dehydrogenase kinase-4 (PDK-4) proteins. These findings demonstrate that luteolin can improve abnormal glucolipid metabolism in angiotensin II/hypoxia-induced hypertrophic H9c2 cells, and its mechanisms are related to the inhibition of HIF-1α expression and subsequent modulation of PPARα-mediated target genes, including CPT-1A, PDK-4, and GLUT-4. [ABSTRACT FROM AUTHOR]

Abstract: Some polyphenols derived from plants may ameliorate hyperlipidemic fatty livers; therefore, we hypothesized that polyphenol-rich Chrysanthemum morifolium extract (CME) may exert an inhibitory effect on the formation of hyperlipidemic fatty livers in mice. This study aimed to examine the effects of CME on lipids in blood and liver and on peroxisome proliferator–activated receptor (PPAR)α–mediated gene expression. Mice with hyperlipidemic fatty livers induced by orally administering high-fat milk via gavage and being simultaneously treated with 75 to 300 mg/kg CME for 6 weeks. After CME addition, the serum total cholesterol levels and hepatic weight coefficients decreased, but no significant reduction in the serum triacylglycerol levels were observed. It is important to note that CME might decrease hepatic lipid accumulation, sterol regulatory element binding protein–1c, and fatty acid synthase expression and increase hepatic PPARα, lipoprotein lipase, and cholesterol 7α-hydroxylase expression. However, the expected reduction in hepatic diacylglycerol acyltransferase mRNA expression was not observed. These findings demonstrate that polyphenol-rich CME may prevent hyperlipidemic fatty liver in mice, and its mechanisms may be related to the modulation of sterol regulatory element binding protein–1c, FAS, lipoprotein lipase, and cholesterol 7α-hydroxylase 1 expression through the PPARα-mediated pathway. [Copyright &y& Elsevier]