A high-fat diet disrupts the hepatic and adipose circadian rhythms and modulates the diurnal rhythm of gut microbiota-derived short-chain fatty acids in gestational mice

Abstract

The prevalence of gestational obesity has reached epidemic proportions. Evidence supported that the interactions between the gut microbiota and circadian clocks far reached, affecting host metabolism. Our study aimed to investigate the effect of a high-fat diet (HF) on the hepatic and adipose circadian rhythms in gestational mice and to explore the role of gut microbiota-derived short-chain fatty acids (SCFAs) in mediating the effects. C57BL/6 female mice were randomly fed a standard chow diet (Ctr) or HF prior to and during pregnancy. Samples were collected every 4 h over 24 h (six time points), and 16S rRNA and metabonomics were carried out. Rhythmic patterns were identified and compared using CircaCompare. The results showed that the HF before and during pregnancy significantly induced obesity and worsen glucose tolerance, insulin sensitivity, and lipid metabolism in the gestational mice. Furthermore, the HF significantly disrupted the rhythmic pattern of hepatic and adipose circadian clock genes and downstream metabolic genes. Importantly, our results revealed that the HF altered the diurnal rhythm of the gut microbiota in a diverse manner, which was assessed across three categories: phase shift, loss rhythmicity, and gained rhythmicity. We report here, for the first time, a parallel alteration of the rhythmic phase of butyric acid and butyrate-producing Clostridiaceae_1, which was confirmed by a positive correlation between them. Overall, our research emphasized the importance of the rhythmicity of gut microbiota-derived SCFAs in mediating circadian disruption in response to the HF in gestational mice, which may provide novel insights into the prevention and treatment of gestational obesity.

Dietary palmitic acid to oleic acid ratio modulates energy metabolism and biological rhythms in young healthy Japanese males

“…Animal studies revealed that a high-fat meal shifts the phase of circadian clock gene expression, and the underlying mechanism for this effect of a high-fat meal on circadian rhythms may be related to the FA composition of the meal, which is often summarised as the palmitic acid to oleic acid ratio (the PA/OA ratio). Other studies revealed that feeding, sleep patterns and clock oscillations in the hypothalamus and peripheral tissues were more strongly affected by meals with a high PA/OA ratio than by those with a low PA/OA ratio (12–16) . In experiments with human hepatocytes, PA, a SFA, inactivated PPAR α (17) and disrupted clock gene expression (18) , while OA, a MUFA, reduced lipotoxicity caused by SFA (19) .…”

Research Progress on the Correlation Between Hypertension and Gut Microbiota

“… 19 In addition, a decrease in the relative abundance of Ruminococcus was observed in the gut following a high-fat diet; Ruminococcus is the main producer of butyrate in the body. 41 Butyrate is an SCFA that plays an active role in maintaining the overall health of the gut. 42 Furthermore, in Dal salt-sensitive rats, the abundance of Veillonellaceae was positively correlated with BP, 20 whereas Enterococci were more common in normotensive individuals.…”

Maternal High‐Fat Diet Results in Long‐Term Sex‐Specific Alterations to Metabolic and Gut Microbial Diurnal Oscillations in Adult Offspring

“…Dosage information:Our previous study found that 5 weeks before and throughout pregnancy HFD altered the metabolic state and gut microbiota rhythm in gestational mice. [6] Meanwhile, it is very common to build the intergenerational mice model with a maternal intervention time of 3-6 weeks before pregnancy. [16,[26][27][28] In other words, 3-6 weeks of pre-pregnancy maternal intervention could have an influence on the offspring's health.…”

“…[ 1 ] Previous studies and our recent study revealed that a high‐fat diet (HFD) contributed to behavioral and molecular circadian disruptions. [ 4–6 ] Consistently, circadian rhythms are closely associated with metabolism, as evidence suggests that circadian disruptions result in obesity and diabetes. [ 1,7 ] However, whether such circadian disruption induced by nutritional challenges is limited to the exposed generation or persists across generations remains unclear.…”