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Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

ABSTRACT: Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac(+)), with metabolic improvement achieved in DIO mice in receipt of vancomycin. However, two phases of weight gain were observed with effects most marked early in the intervention phase. Here, we compare the gut microbial populations at the early relative to the late stages of intervention using a high throughput sequencing-based analysis to understand the temporal relationship between the gut microbiota and obesity. This reveals several differences in microbiota composition over the intervening period. Vancomycin dramatically altered the gut microbiota composition, relative to controls, at the early stages of intervention after which time some recovery was evident. It was also revealed that Bac(+) treatment initially resulted in the presence of significantly higher proportions of Peptococcaceae and significantly lower proportions of Rikenellaceae and Porphyromonadaceae relative to the gut microbiota of L. salivarius UCC118 bacteriocin negative (Bac(-)) administered controls. These differences were no longer evident at the later time. The results highlight the resilience of the gut microbiota and suggest that interventions may need to be monitored and continually adjusted to ensure sustained modification of the gut microbiota.

SUBMITTER: Clarke SF

PROVIDER: S-EPMC3676335 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

Clarke Siobhan F SF Murphy Eileen F EF O'Sullivan Orla O Ross R Paul RP O'Toole Paul W PW Shanahan Fergus F Cotter Paul D PD

PloS one 20130607 6

Links between the gut microbiota and host metabolism have provided new perspectives on obesity. We previously showed that the link between the microbiota and fat deposition is age- and time-dependent subject to microbial adaptation to diet over time. We also demonstrated reduced weight gain in diet-induced obese (DIO) mice through manipulation of the gut microbiota with vancomycin or with the bacteriocin-producing probiotic Lactobacillus salivarius UCC118 (Bac(+)), with metabolic improvement ach ...[more]

PMID: 23762426

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Project description:Background: Disturbance of immunometabolic signaling is a key process involved in the progression of obesity. Microglia-the resident immune cells in the brain, initiate local immune responses. It is known that hypercaloric diets lead to microglial activation. Previously, we observed that hypothalamic microglial cells from mice fed high-fat diet (HFD) lose their day/night rhythm and are constantly activated. However, little is known about daily rhythmicity in microglial circadian, immune and metabolic functions, either in lean or obese conditions. Therefore, we hypothesized that HFD disturbs microglial immunometabolism in a day/night-dependent manner. Methods: Obesity was induced in Wistar rats by feeding them HFD ad libitum for the duration of 8 weeks. Microglia were isolated from HFD- and chow-fed control animals at six time points during 24 h [every 4 h starting 2 h after lights on, i.e., Zeitgeber Time 2 (ZT2)]. Gene expression was evaluated using quantitative RT-PCR. JTK_Cycle software was used to estimate daily rhythmicity. Statistical analysis was performed with two-way ANOVA test. Results: Consumption of the obesogenic diet resulted in a 40 g significantly higher body weight gain in week 8, compared to chow diet (p < 0.0001), associated with increased adiposity. We observed significant rhythmicity of circadian clock genes in microglia under chow conditions, which was partially lost in diet-induced obesity (DIO). Microglial immune gene expression also showed time-of-day differences, which were disrupted in HFD-fed animals. Microglia responded to the obesogenic conditions by a shift of substrate utilization with decreased glutamate and glucose metabolism in the active period of the animals, and an overall increase of lipid metabolism, as indicated by gene expression evaluation. Additionally, data on mitochondria bioenergetics and dynamics suggested an increased energy production in microglia during the inactive period on HFD. Finally, evaluation of monocyte functional gene expression showed small or absent effect of HFD on peripheral myeloid cells, suggesting a cell-specific microglial inflammatory response in DIO. Conclusions: An obesogenic diet affects microglial immunometabolism in a time-of-day dependent manner. Given the central role of the brain in energy metabolism, a better knowledge of daily rhythms in microglial immunometabolism could lead to a better understanding of the pathogenesis of obesity.

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Dataset Information

Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

Publications

Targeting the microbiota to address diet-induced obesity: a time dependent challenge.

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