Dataset Information

A role for ?FosB in calorie restriction-induced metabolic changes.

ABSTRACT: BACKGROUND:Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism. METHODS:After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor ?FosB. The ?FosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted. RESULTS:We show that accumulation of ?FosB in the NAc shell after CR in mice corresponds to a period of increased motivation for high fat reward and reduced energy expenditure. Furthermore, ?FosB overexpression in this region increases instrumental responding for a high fat reward via an orexin-dependent mechanism while also decreasing energy expenditure and promoting adiposity. CONCLUSIONS:These results suggest that ?FosB signaling in NAc mediates adaptive responses to CR.

SUBMITTER: Vialou V

PROVIDER: S-EPMC3125466 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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A role for ΔFosB in calorie restriction-induced metabolic changes.

Vialou Vincent V Cui Huxing H Perello Mario M Mahgoub Melissa M Yu Hana G HG Rush Augustus J AJ Pranav Heena H Jung Saendy S Yangisawa Masashi M Zigman Jeffrey M JM Elmquist Joel K JK Nestler Eric J EJ Lutter Michael M

Biological psychiatry 20110107 2

<h4>Background</h4>Calorie restriction (CR) induces long-term changes in motivation to eat highly palatable food and, in body weight regulation, through an unknown mechanism.<h4>Methods</h4>After a period of CR and refeeding, mice were assessed by behavioral and metabolic studies and for levels of the transcription factor ΔFosB. The ΔFosB levels were then increased specifically in nucleus accumbens (NAc) with viral-mediated gene transfer, and behavioral and metabolic studies were conducted.<h4>R ...[more]

PMID: 21215388

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Project description:Calorie restriction (CR) is accompanied by self-imposed daily restriction of food intake and an extended fasting period between meals. The impact of restricting feeding to the dark or light phase on the effects of CR remains elusive. Here, light-fed CR mice showed physiological changes, such as muscle loss, concomitant with changes in the gut microbiota structure and composition. After switching to ad libitum access to food, light-fed mice had a period of food-craving behavior and short-lived physiological changes, while dark-fed mice displayed lasting changes in fat accumulation, glucose metabolism, intestinal barrier function, and systemic inflammatory markers. Moreover, the gut microbiota was modulated by when the food was consumed, and the most abundant Lactobacillus operational taxonomic unit (OTU) promoted by CR was enhanced in dark-fed mice. After switching to ad libitum feeding, the gut microbiota of dark-fed mice returned to the state resembling that of mice fed normal chow ad libitum, but that of light-fed mice was still significantly different from the other two groups. Together, these data indicate that for CR, restricting food consumption to the active phase brought better metabolic phenotype associated with potentially beneficial structural shifts in the gut microbiota.IMPORTANCE Aberrant feeding patterns whereby people eat more frequently throughout the day and with a bias toward late-night eating are prevalent in society today. However, whether restriction of food to daytime in comparison to nighttime, coupled with restricted calorie intake, can influence gut microbiota, metabolism, and overall health requires further investigation. We surveyed the effects of the shift in feeding time on gut microbiota and metabolic phenotype in calorie-restricted mice and found that avoiding eating during the rest period may generate more beneficial effects in mice. This work strengthens the evidence for using "when to eat" as an intervention to improve health during calorie restriction.

Project description:Background: The mechanisms responsible for calorie restriction (CR)-induced improvement in insulin sensitivity (IS) have not been fully elucidated. Greater insight can be achieved through deep biological phenotyping of subjects undergoing CR, and integration of big data. Materials and Methods: An integrative approach was applied to investigate associations between change in IS and factors from host, microbiota, and lifestyle after a 6-week CR period in 27 overweight or obese adults (ClinicalTrials.gov: NCT01314690). Partial least squares regression was used to determine associations of change (week 6 - baseline) between IS markers and lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics of serum, urine and feces, and gut microbiota composition. ScaleNet, a network learning approach based on spectral consensus strategy (SCS, developed by us) was used for reconstruction of biological networks. Results: A spectrum of variables from lifestyle factors (10 nutrients), gut microbiota (10 metagenomics species), and host multi-omics (metabolic features: 84 from serum, 73 from urine, and 131 from feces; and 257 sAT gene probes) most associated with IS were identified. Biological network reconstruction using SCS, highlighted links between changes in IS, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species (MGS). Linear regression analysis to model how changes of select variables over the CR period contribute to changes in IS, showed greatest contributions from gut MGS and fiber intake. Conclusion: This work has enhanced previous knowledge on links between host glucose homeostasis, lifestyle factors and the gut microbiota, and has identified potential biomarkers that may be used in future studies to predict and improve individual response to weight-loss interventions. Furthermore, this is the first study showing integration of the wide range of data presented herein, identifying 115 variables of interest with respect to IS from the initial input, consisting of 9,986 variables. Clinical Trial Registration: clinicaltrials.gov (NCT01314690).

Dataset Information

A role for ?FosB in calorie restriction-induced metabolic changes.

Publications

A role for ΔFosB in calorie restriction-induced metabolic changes.

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