Complex tumour ecosystem comprising tumour cells and its associated tumour microenvironment (TME) constantly influence the tumoural behaviour and ultimately impact therapy failure, disease progression, recurrence and poor overall survival of patients. Crosstalk between tumour cells and TME amplifies the complexity by creating metabolic changes such as hypoxic environment and nutrient fluctuations. These changes in TME initiate stem cell-like programmes in cancer cells, contribute to tumoural heterogeneity and increase tumour robustness. Recent studies demonstrate the multifaceted role of autophagy in promoting fibroblast production, stemness, cancer cell survival during longer periods of dormancy, eventual growth of metastatic disease and disease resistance. Recent ongoing studies examine autophagy/mitophagy as a powerful survival strategy in response to environmental stress including nutrient deprivation, hypoxia and environmental stress in TME. It prevents irreversible senescence, promotes dormant stem-like state, induces epithelial–mesenchymal transition and increases migratory and invasive potential of tumour cells. The present review discusses various theories and mechanisms behind the autophagy-dependent induction of cancer stem cell (CSC) phenotype. Given the role of autophagic functions in CSC aggressiveness and therapeutic resistance, various mechanisms and studies based on suppressing cellular plasticity by blocking autophagy as a powerful therapeutic strategy to kill tumour cells are discussed.

The goal of this narrative review is to summarise the current knowledge and limitations related to the anti-inflammatory effects of tomato, tomato-derived products and lycopene in the context of metabolic inflammation associated to cardiometabolic diseases. The potential of tomato and tomato-derived product supplementation is supported by animal and in vitro studies. In addition, intervention studies provide arguments in favour of a limitation of metabolic inflammation. This is also the case for observational studies depicting inverse association between plasma lycopene levels and inflammation. Nevertheless, current data of intervention studies are mixed concerning the anti-inflammatory effect of tomato and tomato-derived products and are not in favour of an anti-inflammatory effect of pure lycopene in humans. From epidemiological to mechanistic studies, this review aims to identify limitations of the current knowledge and gaps that remain to be filled to improve our comprehension in contrasted anti-inflammatory effects of tomato, tomato-derived products and pure lycopene.

A 60-d feeding trial was conducted to explore the potential regulatory effects of dietary Clostridium butyricum cultures (CBC) supplementation in high-carbohydrate diet (HCD) on carbohydrate utilisation, antioxidant capacity and intestinal microbiota of largemouth bass. Triplicate groups of largemouth bass (average weight 35·03 ± 0·04 g), with a destiny of twenty-eight individuals per tank, were fed low-carbohydrate diet and HCD supplemented with different concentration of CBC (0 %, 0·25 %, 0·50 % and 1·00 %). The results showed that dietary CBC inclusion alleviated the hepatic glycogen accumulation induced by HCD intake. Additionally, the expression of hepatic ampkα1 and insulin signaling pathway-related genes (ira, irb, irs, p13kr1 and akt1) increased linearly with dietary CBC inclusion, which might be associated with the activation of glycolysis-related genes (gk, pfkl and pk). Meanwhile, the expression of intestinal SCFA transport-related genes (ffar3 and mct1) was significantly increased with dietary CBC inclusion. In addition, the hepatic antioxidant capacity was improved with dietary CBC supplementation, as evidenced by linear decrease in malondialdehyde concentration and expression of keap1, and linear increase in antioxidant enzyme activities (total antioxidative capacity, total superoxide dismutase and catalase) and expression of antioxidant enzyme-related genes (nrf2, sod1, sod2 and cat). The analysis of bacterial 16S rRNA V3–4 region indicated that dietary CBC inclusion significantly reduced the enrichment of Firmicutes and potential pathogenic bacteria genus Mycoplasma but significantly elevated the relative abundance of Fusobacteria and Cetobacterium. In summary, dietary CBC inclusion improved carbohydrate utilization, antioxidant capacity and intestinal microbiota of largemouth bass fed HCD.

The current study aims to confirm the positive effects of dietary nano-Se on nutrients deposition and muscle fibre formation in grass carp fed with high-fat diet (HFD) before overwintering and to reveal its possible molecular mechanism. The lipid deposition, protein synthesis and muscle fibre formation in grass carp fed with regular diet (RD), HFD or HFD supplemented with nano-Se (0·3 or 0·6 mg/kg) for 60 d were tested. Results show that nano-Se significantly reduced lipid content, dripping loss and fibre diameter (P < 0·05), but increased protein content, post-mortem pH24 h and muscle fibre density (P < 0·05) in muscle of grass carp fed with HFD. Notably, dietary nano-Se decreased lipid deposition in the muscle by regulating amp-activated protein kinase activity and increased protein synthesis and fibre formation in muscle by activating target of rapamycin and myogenic determining factors pathways. In summary, dietary nano-Se can regulate the nutrients deposition and muscle fibre formation in grass carp fed with HFD, which exhibit potential benefit for improving flesh quality of grass carp fed with HFD.

The term ‘autophagy’ literally translates to ‘self-eating’ and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they might be connected to both aging and the onset and progression of disease. Additionally, we go over the most recent preclinical data supporting the use of autophagy modulators as age-related illnesses including cancer, cardiovascular and neurodegenerative diseases, and metabolic dysfunction. It is crucial to discover important targets in the autophagy pathway in order to create innovative therapies that effectively target autophagy. Natural products have pharmacological properties that can be therapeutically advantageous for the treatment of several diseases and they also serve as valuable sources of inspiration for the development of possible new small-molecule drugs. Indeed, recent scientific studies have shown that several natural products including alkaloids, terpenoids, steroids, and phenolics, have the ability to alter a number of important autophagic signalling pathways and exert therapeutic effects, thus, a wide range of potential targets in various stages of autophagy have been discovered. In this review, we summarised the naturally occurring active compounds that may control the autophagic signalling pathways.

Obesity remains a serious relevant public health concern throughout the world despite related countermeasures being well understood (i.e. mainly physical activity and an adjusted diet). Among different nutritional approaches, there is a growing interest in ketogenic diets (KD) to manipulate body mass (BM) and to enhance fat mass loss. KD reduce the daily amount of carbohydrate intake drastically. This results in increased fatty acid utilisation, leading to an increase in blood ketone bodies (acetoacetate, 3-β-hydroxybutyrate and acetone) and therefore metabolic ketosis. For many years, nutritional intervention studies have focused on reducing dietary fat with little or conflicting positive results over the long term. Moreover, current nutritional guidelines for athletes propose carbohydrate-based diets to augment muscular adaptations. This review discusses the physiological basis of KD and their effects on BM reduction and body composition improvements in sedentary individuals combined with different types of exercise (resistance training or endurance training) in individuals with obesity and athletes. Ultimately, we discuss the strengths and the weaknesses of these nutritional interventions together with precautionary measures that should be observed in both individuals with obesity and athletic populations. A literature search from 1921 to April 2021 using Medline, Google Scholar, PubMed, Web of Science, Scopus and Sportdiscus Databases was used to identify relevant studies. In summary, based on the current evidence, KD are an efficient method to reduce BM and body fat in both individuals with obesity and athletes. However, these positive impacts are mainly because of the appetite suppressive effects of KD, which can decrease daily energy intake. Therefore, KD do not have any superior benefits to non-KD in BM and body fat loss in individuals with obesity and athletic populations in an isoenergetic situation. In sedentary individuals with obesity, it seems that fat-free mass (FFM) changes appear to be as great, if not greater, than decreases following a low-fat diet. In terms of lean mass, it seems that following a KD can cause FFM loss in resistance-trained individuals. In contrast, the FFM-preserving effects of KD are more efficient in endurance-trained compared with resistance-trained individuals.

Tremendous progress has been made in the field of ferroptosis since this regulated cell death process was first named in 2012. Ferroptosis is initiated upon redox imbalance and driven by excessive phospholipid peroxidation. Levels of multiple intracellular nutrients (iron, selenium, vitamin E and coenzyme Q10) are intimately related to the cellular antioxidant system and participate in the regulation of ferroptosis. Dietary intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) regulates ferroptosis by directly modifying the fatty acid composition in cell membranes. In addition, amino acids and glucose (energy stress) manipulate the ferroptosis pathway through the nutrient-sensitive kinases mechanistic target of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). Understanding the molecular interaction between nutrient signals and ferroptosis sensors might help in the identification of the roles of ferroptosis in normal physiology and in the development of novel pharmacological targets for the treatment of ferroptosis-related diseases.

The current epidemic of type 2 diabetes mellitus (T2DM) significantly affects human health worldwide. Activation of brown adipocytes and browning of white adipocytes are considered as a promising molecular target for T2DM treatment. Mulberry leaf, a traditional Chinese medicine, has been demonstrated to have multi-biological activities, including anti-diabetic and anti-inflammatory effects. Our experimental results showed that mulberry leaf significantly alleviated the disorder of glucose and lipid metabolism in T2DM rats. In addition, mulberry leaf induced browning of inguinal white adipose tissue (IWAT) by enhancing the expressions of brown-mark genes as well as beige-specific genes, including uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα), PRD1-BF-1-RIZ1 homologous domain containing protein 16 (PRDM16), cell death inducing DFFA-like effector A (Cidea), CD137 and transmembrane protein 26 (TMEM26). Mulberry leaf also activated brown adipose tissue (BAT) by increasing the expressions of brown-mark genes including UCP1, PGC-1α, PPARα, PRDM16 and Cidea. Moreover, mulberry leaf enhanced the expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) genes that are responsible for mitochondrial biogenesis in IWAT and BAT. Importantly, mulberry leaf also increased the expression of UCP1 and carnitine palmitoyl transferase 1 (CPT-1) proteins in both IWAT and BAT via a mechanism involving AMP-activated protein kinase (AMPK) and PGC-1α pathway. In conclusion, our findings identify the role of mulberry leaf in inducing adipose browning, indicating that mulberry leaf may be used as a candidate browning agent for the treatment of T2DM.

This work aimed to evaluate the effects of whey protein concentrate (WPC) admixtured of curcumin on metabolic control, inflammation and oxidative stress in Wistar rats submitted to exhaustive exercise. A total of forty-eight male rats were divided into six experimental groups (n 8): standard diet group (AIN-93M), standard diet submitted to exhaustion test group (AIN-93M ET), WPC admixtured of curcumin group (WPC + CCM), WPC + CCM submitted to exhaustion test group (WPC + CCM ET), CCM group and CCM subjected to exhaustion test group (CCM ET). The swimming exhaustion test was performed after 4 weeks of experiment. The consumption of WPC + CCM as well as isolated CCM did not alter the biometric measurements, the animals’ food consumption and the hepatic and kidney function, as well as the protein balance of the animals (P > 0·05), but reduced the glycaemia and the gene expression of TNF-α and IL-6 and increased the expression of IL-10 (P < 0·05). The animals that were submitted to the exhaustion test (AIN-93M ET) showed higher aspartate aminotransferase values when compared to the animals that did not perform the exercise (AIN-93 M) (P < 0·05). WPC + CCM reduced the concentration of nitric oxide, carbonylated protein and increased the concentration of catalase (P < 0·05). Both (WPC + CCM and CCM) were able to increase the concentrations of superoxide dismutase (P < 0·05). We concluded that the WPC admixtured of CCM represents a strategy capable of decreasing blood glucose and oxidative and inflammatory damage caused by exhaustive physical exercise in swimming.

A12-week experiment was conducted to evaluate the influences of thiamine ongrowth performance, and intestinal mitochondrial biogenesis and function of Megalobramaamblycephala fed a high-carbohydrate (HC) diet. Fish (24·73 (sem 0·45) g) were randomly assigned to one of four diets: two carbohydrate (CHO) levels (30 and 45 %) and two thiamine levels (0 and 1·5 mg/kg). HC diets significantly decreased DGC, GRMBW, FIMBW, intestinal activities of amylase, lipase, Na+, K+-ATPase, CK, complexes I, III and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK: T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, mitochondrial transcription factor A, Opa-1, ND-1 and COX-1 and 2, while the opposite was true for ATP, AMP and reactive oxygen species, and the transcriptions of dynamin-related protein-1, fission-1 and mitochondrial fission factor. Dietarythiamine concentrations significantly increased DGC, GRMBW, intestinal activities of amylase, Na+, K+-ATPase, CK, complexes I and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK:T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, Opa-1, ND-1, COX-1 and 2, SGLT-1 and GLUT-2. Furthermore, a significant interaction between dietary CHO and thiamine was observed in DGC, GRMBW, intestinal activities of amylase, CK, complexes I and IV, ΔΨm, the AMP:ATP ratio, the P-AMPK:T-AMPK ratio, PGC-1β protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1β, Opa-1, COX-1 and 2, SGLT-1 and GLUT-2. Overall, thiamine supplementation improved growth performance, and intestinal mitochondrial biogenesis and function of M. amblycephala fed HC diets.

Previous nutritional studies have shown that insulin regulation is different between DT and A strains of gibel carp. As leptin plays a pivotal role in the effects of insulin, we hypothesised that leptin regulation of glucose and lipid metabolism would differ between the two strains. To test our hypothesis, recombinant human leptin was injected into two strains. The results showed that leptin activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT), AMP-activated protein kinase–acetyl coenzyme A carboxylase and Janus kinase 2 (JAK2)–signal transducer and activator of transcription (STAT) signalling pathways in both strains. Hypoglycaemia induced by leptin might be due to higher glucose uptake by the liver and muscles together with enhanced glycolytic potential and reduced gluconeogenic potential. Decreased lipogenesis and up-regulated fatty acid oxidation were induced by leptin. In terms of genotype, the PI3K–AKT signalling pathway was more strongly activated by leptin in the muscle tissue of the A strain, as reflected by the heightened phosphorylation of AKT. Furthermore, glycogen content, glycolytic enzyme activity and gluconeogenic capability were higher in the A strain than the DT strain. Strain A had higher levels of fatty acid synthesis and lipolytic capacity in the liver than the DT strain, but the opposite was true in white muscle. Regarding leptin–genotype interactions, the DT strain displayed stronger regulation of glucose metabolism in the liver by leptin as compared with the A strain. Moreover, a more active JAK2–STAT signalling pathway accompanied by enhanced inhibition of fatty acid synthesis by leptin was observed in the DT strain. Overall, the regulation of glucose and lipid metabolism by leptin differed between the two strains, as expected.

Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.

Mitochondria play an important role in a number of fundamental cellular processes, including energy production, biosynthetic pathways and cellular oxidoreductive homeostasis (redox status), and their dysfunction can lead to numerous pathophysiological consequences. As the biochemical mechanisms orchestrating mitochondrial metabolism and redox homeostasis are functionally linked, mitochondria have been identified as a potential therapeutic target. Consequently, considerable effort has been made to evaluate the efficacy of natural compounds that modulate mitochondrial function. Molecules produced by plants (for example, polyphenols and isothiocyanates) have been shown to modulate mitochondrial metabolism/biogenesis and redox status; however, despite the existence of a functional link, few studies have considered the combined efficacy of these mitochondrial functions. The present review provides a complete overview of the molecular pathways involved in modulating mitochondrial metabolism/biogenesis and redox status. Crosstalk between these critical mechanisms is also discussed, whilst major data from the literature regarding their antioxidant abilities are described and critically analysed. We also provide a summary of recent evidence regarding the ability of several plant-derived compounds to target these mitochondrial functions. An in-depth understanding of the functional link between mitochondrial metabolism/biogenesis and redox status could facilitate the analysis of the biological effects of natural compounds as well as the development of new therapeutic approaches.

Dietary intake and nutritional status is an important environmental factor which can modulate metabolic-inflammation. In recent years, research has made significant advances in terms of understanding the impact of dietary components on metabolic-inflammation, within the context of obesity, type-2 diabetes (T2D) and CVD risk. Our work demonstrated that different fatty acids differentially modulate metabolic-inflammation, initially focusing on Nod-like receptor family, pyrin domain-containing three protein (NLRP3) inflammasome mediated IL-1β biology and insulin signalling. However, the paradigm is more complex, wherein data from the immunology field clearly show that nature of cellular energy metabolism is a key determinant of inflammation. Whilst metabolic-inflammation is a critical biological interaction, there is a paucity of data in relation to the nature and the extent to which nutritional status affects metabolic-inflammation. The complex paradigm will be discussed within the context of if/how dietary components, in particular fatty acids, may modulate obesity, T2D and CVD risk, via inflammatory and metabolic processes.

Procyanidins have been reported to possess potential for the prevention of hyperglycaemia. However, there are very few data for procyanidins about the difference the degree of polymerisation (DP) has on anti-hyperglycaemic effects. Moreover, the underlying molecular mechanisms by which procyanidins suppress hyperglycaemia are not yet fully understood. In the present study, we prepared procyanidin fractions with different DP, namely low-DP (DP≤3) and high-DP (DP≥4) fractions, from a cacao liquor procyanidin-rich extract (CLPr). These fractions were administered orally to Institute of Cancer Research (ICR) mice and their anti-hyperglycaemic effects were examined. We found that CLPr and its fractions prevent postprandial hyperglycaemia accompanied by an increase in the plasma glucagon-like peptide-1 (GLP-1) level with or without glucose load. In the absence of glucose load, both fractions increased the plasma insulin level and activated its downstream signalling pathway in skeletal muscle, resulting in promotion of the translocation of GLUT4. Phosphorylation of AMP-activated protein kinase (AMPK) was also involved in the promotion of GLUT4 translocation. High- and low-DP fractions showed a similar activation of insulin and AMPK pathways. In conclusion, cacao liquor procyanidins prevent hyperglycaemia by promoting GLUT4 translocation in skeletal muscle, and both the GLP-1-activated insulin pathway and the AMPK pathway are involved in the underlying molecular mechanism.

Energy restriction (ER) has been widely studied as a novel intervention, and its ability to prolong life has been fully demonstrated. For example, ER can significantly extend the lifespans of model flies, worms, rodents and other mammals. The role of ER in renal protection has also been elucidated. In preclinical studies, adjusting total energy intake or consumption of specific nutrients has prophylactic or therapeutic effects on ageing-related kidney disease and acute and chronic kidney injury. Amino acid restriction has gradually attracted attention. ER mimetics have also been studied in depth. The protective mechanisms of ER and ER mimetics for renal injury include increasing AMP-activated protein kinase and sirtuin type 1 (Sirt1) levels and autophagy and reducing mammalian target of rapamycin, inflammation and oxidative stress. However, the renal protective effect of ER has mostly been investigated in rodent models, and the role of ER in patients cannot be determined due to the lack of large randomised controlled trials. To protect the kidney, the mechanism of ER must be thoroughly researched, and more accurate diet or drug interventions need to be identified.

Benefits of resistant starch (RS) consumption on host physiology encompass microbial activity-derived attenuation of intestinal inflammation. However, little is known about anti-inflammatory properties of RS of type 4. This study compared the effects of transglycosylated starch (TGS) consumption on the jejunal barrier function and expression of genes related to inflammation, barrier function and the mucosal defence in jejunum, ileum, caecum and colon of pigs. Moreover, interactions of TGS-induced alterations in bacterial metabolites and composition with host mucosal responses were assessed using sparse partial least squares regression and relevance network analysis. Intestinal samples were collected after pigs (n 8/diet; 4 months of age) were fed the experimental diets for 10 d. Consumption of TGS did not modify jejunal barrier function and gene expression. By contrast, TGS down-regulated the caecal expression of zonula occludens-1 and mucin 2 and of genes within the toll-like receptor 4 and NF-κB pro-inflammatory signalling cascade. Relevance networks revealed a microbiome signature on ileal, caecal and colonic mucosal signalling as TGS-derived changes in bacterial genera and fermentation acids, such as propionic acid, correlated with the differently expressed genes in ileum, caecum and colon of pigs. In conclusion, the present findings suggest certain anti-inflammatory capabilities of TGS by down-regulating the expression of pro-inflammatory pathways in the caecal mucosa, which seems to be mediated, at least in part, by TGS-induced changes in microbial action in the large intestine.

Leucine plays an important role in promoting muscle protein synthesis and muscle remodelling. However, what percentage of leucine is appropriate in creep feed and what proteome profile alterations are caused by dietary leucine in the skeletal muscle of piglets remain elusive. In this case, we applied isobaric tags for relative and absolute quantitation to analyse the proteome profile of the longissimus dorsi muscles of weanling piglets fed a normal leucine diet (NL; 1·66 % leucine) and a high-leucine diet (HL; 2·1 % leucine). We identified 157 differentially expressed proteins between these two groups. Bioinformatics analysis of these proteins exhibited the suppression of oxidative phosphorylation and fatty acid β-oxidation, as well as the activation of glycolysis, in the HL group. For further confirmation, we identified that SDHB, ATP5F1, ACADM and HADHB were significantly down-regulated (P<0·01, except ATP5F1, P<0·05), whereas the glycolytic enzyme pyruvate kinase was significantly up-regulated (P<0·05) in the HL group. We also show that enhanced muscle protein synthesis and the transition from slow-to-fast fibres are altered by leucine. Together, these results indicate that leucine may alter energy metabolism and promote slow-to-fast transitions in the skeletal muscle of weanling piglets.

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.