Daytime restricted feeding modifies the daily regulation of fatty acidβ-oxidation and the lipoprotein profile in rats

Abstract

Daytime restricted feeding (2 h of food access from 12.00 to 14.00 hours for 3 weeks) is an experimental protocol that modifies the relationship between metabolic networks and the circadian molecular clock. The precise anatomical locus that controls the biochemical and physiological adaptations to optimise nutrient use is unknown. We explored the changes in liver oxidative lipid handling, such as β-oxidation and its regulation, as well as adaptations in the lipoprotein profile. It was found that daytime restricted feeding promoted an elevation of circulating ketone bodies before mealtime, an altered hepatic daily rhythmicity of 14CO2 production from radioactive palmitic acid, and an up-regulation of the fatty acid oxidation activators, the α-subunit of AMP-activated protein kinase (AMPK), the deacetylase silent mating type information regulation homolog 1, and the transcriptional factor PPARγ-1α coactivator. An increased localisation of phosphorylated α-subunit of AMPK in the periportal hepatocytes was also observed. Liver hepatic lipase C, important for lipoprotein transformation, showed a change of daily phase with a peak at the time of food access. In serum, there was an increase of LDL, which was responsible for a net elevation of circulating cholesterol. We conclude that our results indicate an enhanced fasting response in the liver during daily synchronisation to food access, which involves altered metabolic and cellular control of fatty acid oxidation as well a significant elevation of serum LDL. These adaptations could be part of the metabolic input that underlies the expression of the food-entrained oscillator.

Time-Restricted Feeding Reduces the Detrimental Effects of a High-Fat Diet, Possibly by Modulating the Circadian Rhythm of Hepatic Lipid Metabolism and Gut Microbiota

“…Studies in as early as 1980s proposed that reducing food availability protected against aging and improved life span in mice (3,4). Recent researches as well as our studies in rodent animals concerning TRF are increasingly revealing its various beneficial effects, including preventing dietinduced obesity and its associated metabolic disorders (1,(5)(6)(7)(8), preventing inflammatory bowel diseases and colorectal cancer and neurodegenerative disorders (9,10), and alleviating hepatic ischemia reperfusion injury (11). The rhythm of feeding can greatly influence the development of liver steatosis and remodel the hepatic circadian metabolome, which suggests a potential mechanism of TRF (12,13).…”

Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CCl4-Treated Fibrotic Mice

“…Liver tissue was fixed in 10% formalin, according to a previously reported protocol [43]. Liver slices of 5 µm were incubated with primary antibody against P2Y2R (Alomone Labs, Jerusalem, Israel) at 1:150 dilution and with secondary antibody donkey anti-Rabbit IgG Cy3 (Thermo Fisher Scientific, Wilmington, DE, USA).…”

Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase

“…This fasting/feeding cycle modifies the temporal organization of the liver, kidney, heart, and pancreas activities independently of the SCN [14]. This is achieved through changes in the temporal expression of enzymes involved in the metabolism of lipids, glucose, and urea during the food access period [15][16][17][18].…”