Transcriptome Analysis of Compensatory Growth and Meat Quality Alteration after Varied Restricted Feeding Conditions in Beef Cattle.

Compensatory growth (CG) is a physiological response that accelerates growth following a period of nutrient limitation, with the potential to improve growth efficiency and meat quality in cattle. However, the underlying molecular mechanisms remain poorly understood. In this study, 60 Huaxi cattle were divided into one ad libitum feeding (ALF) group and two restricted feeding groups (75% restricted, RF75; 50% restricted, RF50) undergoing a short-term restriction period followed by evaluation of CG. Detailed comparisons of growth performance during the experimental period, as well as carcass and meat quality traits, were conducted, complemented by a comprehensive transcriptome analysis of the longissimus dorsi muscle using differential expression analysis, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and weighted correlation network analysis (WGCNA). The results showed that irrespective of the restriction degree, the restricted animals exhibited CG, achieving final body weights comparable to the ALF group. Compensating animals showed differences in meat quality traits, such as pH, cooking loss, and fat content, compared to the ALF group. Transcriptomic analysis revealed 57 genes and 31 pathways differentially regulated during CG, covering immune response, acid-lipid metabolism, and protein synthesis. Notably, complement-coagulation-fibrinolytic system synergy was identified as potentially responsible for meat quality optimization in RF75. This study provides novel and valuable genetic insights into the regulatory mechanisms of CG in beef cattle.

Food deprivation reduces sensitivity of liver Igf1 synthesis pathways to growth hormone in juvenile gopher rockfish (Sebastes carnatus).

Growth hormone (Gh) regulates growth in part by stimulating the liver to synthesize and release insulin-like growth factor-1 (Igf1), which then promotes somatic growth. However, for fish experiencing food limitation, elevated blood Gh can occur even with low circulating Igf1 and slow growth, suggesting that nutritional stress can alter the sensitivity of liver Igf1 synthesis pathways to Gh. Here, we examined how recent feeding experience affected Gh regulation of liver Igf1 synthesis pathways in juvenile gopher rockfish (Sebastes carnatus) to illuminate mechanisms underlying the nutritional modulation of Igf1 production. Juvenile gopher rockfish were maintained under conditions of feeding or complete food deprivation (fasting) for 14 d and then treated with recombinant sea bream (Sparus aurata) Gh or saline control. Gh upregulated hepatic igf1 mRNA levels in fed fish but not in fasted fish. The liver of fasted rockfish also showed a lower relative abundance of gene transcripts encoding teleost Gh receptors 1 (ghr1) and 2 (ghr2), as well as reduced protein levels of phosphorylated janus tyrosine kinase 2 (pJak2) and signal transducer and activator of transcription 5 (pStat5), which function to induce igf1 gene transcription following Gh binding to Gh receptors. Relative hepatic mRNA levels for suppressors of cytokine signaling (Socs) genes socs2, socs3a, and socs3b were also lower in fasted rockfish. Socs2 can suppress Gh activation of Jak2/Stat5, and fasting-related variation in socs expression may reflect modulated inhibitory control of igf1 gene transcription. Fasted rockfish also had elevated liver mRNA abundances for lipolytic hormone-sensitive lipase 1 (hsl1) and Igf binding proteins igfbp1a, -1b and -3a, reduced liver mRNAs encoding igfbp2b and an Igfbp acid labile subunit-like (igfals) gene, and higher transcript abundances for Igf1 receptors igf1ra and igf1rb in skeletal muscle. Together, these findings suggest that food deprivation impacts liver Igf1 responsiveness to Gh via multiple mechanisms that include a downregulation of hepatic Gh receptors, modulation of the intracellular Jak2/Stat5 transduction pathway, and possible shifts in Socs-inhibitory control of igf1 gene transcription, while also demonstrating that these changes occur in concert with shifts in liver Igfbp expression and muscle Gh/Igf1 signaling pathway components.

Expression Level Changes in Serotonin Transporter are Associated with Food Deprivation in the Pond Snail Lymnaea stagnalis.

In the pond snail Lymnaea stagnalis, serotonin (5-HT) plays an important role in feeding behavior and its associated learning (e.g., conditioned taste aversion: CTA). The 5-HT content in the central nervous system (CNS) fluctuates with changes in the nutritional status, but it is also expected to be influenced by changes in the serotonin transporter (SERT) expression level. In the present study, we identified SERT in Lymnaea and observed its localization in 5-HTergic neurons, including the cerebral giant cells (CGCs) in the cerebral ganglia and the pedal A cluster neurons and right and left pedal dorsal 1 neurons in the pedal ganglia by in situ hybridization. Real-time PCR revealed that the SERT mRNA expression level was lower under severe food deprivation than under mild food deprivation in the whole CNS as well as in a single CGC. These results inversely correlated with previous data that the 5-HT content in the CNS was higher in the severely food-deprived state than in the mildly food-deprived state. Furthermore, in single CGCs, we observed that the 5-HT level was significantly increased in the severely food-deprived state compared with the mildly food-deprived state. Our present findings suggest that changes in the SERT expression level associated with food deprivation may affect 5-HT signaling, probably contributing to learning and memory mechanisms in Lymnaea.

No food for thought: an intermediate level of food deprivation enhances memory in Lymnaea stagnalis.

Nutritional status plays an important role in cognitive functioning, but there is disagreement on the role that food deprivation plays in learning and memory. In this study, we investigated the behavioral and transcriptional effects induced by different lengths of food deprivation: 1 day, which is a short time period of food deprivation, and 3 days, which is an 'intermediate' level of food deprivation. Snails were subjected to different feeding regimens and then trained for operant conditioning of aerial respiration, where they received a single 0.5 h training session followed by a long-term memory (LTM) test 24 h later. Immediately after the memory test, snails were killed and the expression levels of key genes for neuroplasticity, energy balance and stress response were measured in the central ring ganglia. We found that 1 day of food deprivation was not sufficient to enhance snails' LTM formation and subsequently did not result in any significant transcriptional effects. However, 3 days of food deprivation resulted in enhanced LTM formation and caused the upregulation of neuroplasticity and stress-related genes and the downregulation of serotonin-related genes. These data provide further insight into how nutritional status and related molecular mechanisms impact cognitive function.

CNS serotonin content mediating food deprivation-enhanced learning is regulated by hemolymph tryptophan concentration and autophagic flux in the pond snail.

Nutritional status affects cognitive function in many types of organisms. In the pond snail Lymnaea stagnalis, 1 day of food deprivation enhances taste aversion learning ability by decreasing the serotonin (5-hydroxytryptamin; 5-HT) content in the central nervous system (CNS). On the other hand, after 5 days of food deprivation, learning ability and the CNS 5-HT concentration return to basal levels. How food deprivation leads to alterations of 5-HT levels in the CNS, however, is unknown. Here, we measured the concentration of the 5-HT precursor tryptophan in the hemolymph and CNS, and demonstrated that the CNS tryptophan concentration was higher in 5-day food-deprived snails than in non-food-deprived or 1-day food-deprived snails, whereas the hemolymph tryptophan concentration was not affected by the duration of food deprivation. This finding suggests the existence of a mediator of the CNS tryptophan concentration independent of food deprivation. To identify the mediator, we investigated autophagic flux in the CNS under different food deprivation conditions. We found that autophagic flux was significantly upregulated by inhibition of the tropomyosin receptor kinase (Trk)-Akt-mechanistic target of rapamycin complex 1 (MTORC1) pathway in the CNS of 5-day food-deprived snails. Moreover, when autophagy was inhibited, the CNS 5-HT content was significantly downregulated in 5-day food-deprived snails. Our results suggest that the hemolymph tryptophan concentration and autophagic flux in the CNS cooperatively regulate learning ability affected by different durations of food deprivation. This mechanism may underlie the selection of behaviors appropriate for animal survival depending on the degree of nutrition.

Multiple entrained oscillator model of food anticipatory circadian rhythms.

For many animal species, knowing when to look for food may be as important as knowing where to look. Rats and other species use a feeding-responsive circadian timing mechanism to anticipate, behaviorally and physiologically, a predictable daily feeding opportunity. How this mechanism for anticipating a daily meal accommodates more than one predictable mealtime is unclear. Rats were trained to press a lever for food, and then limited to one or more daily meals at fixed or systematically varying times of day. The rats were able to anticipate up to 4 of 4 daily meals at fixed times of day and two 'daily' meals recurring at 24 h and 26 h intervals. When deprived of food, in constant dark, lever pressing recurred for multiple cycles at expected mealtimes, consistent with the periodicity of the prior feeding schedule. Anticipation did not require the suprachiasmatic nucleus circadian pacemaker. The anticipation rhythms could be simulated using a Kuramoto model in which clusters of coupled oscillators entrain to specific mealtimes based on initial phase and intrinsic circadian periodicity. A flexibly coupled system of food-entrainable circadian oscillators endows rats with adaptive plasticity in daily programming of foraging activity.

Differences in bovine placentome blood vessel density and transcriptomics in a mid to late-gestating maternal nutrient restriction model.

INTRODUCTION: Prenatal development is reliant on a functioning placenta, which can be influenced by maternal nutrition. Moreover, the variation in cotyledonary capacity within an animal has not been fully examined to date. Therefore, the purpose of this study was to determine the effect of (1) placentome size and (2) maternal nutrient restriction on molecular, microscopic, and macroscopic features of bovine placentomes during late gestation. METHODS: Pregnant cows (n = 6) were placed into one of 2 treatments: CON (100% NRC) vs RES (60% of NRC) from day 140 until slaughter at day 240 of gestation. Placentomes of various sizes were perfused to assess macroscopic blood vessel density of the cotyledon. Microscopic imaging and RNA extraction for sequencing was performed. RESULTS: Macroscopic blood vessel density relative to placentome weight was not different (P = 0.42) among small, medium, or large placentomes. Cotyledonary microscopic blood vessel number, area, and perimeter was increased (P < 0.005) in high versus low blood perfusion areas. Differential expressed gene (DEG) analysis showed 209 upregulations and 168 downregulations in the RES group (P ≤ 0.0001). Gene Ontology (GO) analysis showed that downregulated enriched terms were involved in blood vessel and mesenchymal stem cells development, whereas upregulated enriched terms were involved with translation and ribosomal function. DISCUSSION: This study demonstrates that placentome function is uniform across various placentome sizes within an animal. However, microscopic heterogeneity exists within each placentome. Maternal nutrient constraints alter placental transcriptomics which may yield compensatory mechanisms involved in nutrient transport including increased perimeter.

Using an invertebrate model to investigate the mechanisms of short-term memory deficits induced by food deprivation.

Although prolonged food deprivation is known to cause memory deficits, the underlying mechanisms are only partially understood. In this study, we began to investigate the cellular substrates of food deprivation-induced memory impairments in the invertebrate Aplysia. Following a single trial of noxious stimuli, Aplysia concurrently express short-term sensitization (an elementary form of learning in which withdrawal reflexes are enhanced) and short-term feeding suppression for at least 15 min. Cellular correlates of sensitization and feeding suppression include increased excitability of the tail sensory neurons (TSNs) controlling the withdrawal reflexes, and decreased excitability of feeding decision-making neuron B51, respectively. Recently, 14 days of food deprivation (14DFD) was reported to break the co-expression of sensitization and feeding suppression in Aplysia without health deterioration. Specifically, under 14DFD, sensitization was completely prevented while feeding suppression was present albeit attenuated. This study explored the cellular mechanisms underlying the absent sensitization and reduced feeding suppression under 14DFD. A reduced preparation was used to evaluate the short-term cellular modifications induced by delivering an aversive training protocol in vitro. TSN excitability failed to increase following in vitro training under 14DFD, suggesting that the lack of sensitization may be a consequence of the fact that TSN excitability failed to increase. B51 excitability also failed to decrease following in vitro training, indicating that additional neurons may contribute to the conserved albeit reduced feeding suppression in 14DFD animals. This study lays the foundations for the future use of the Aplysia model system to investigate the mechanisms underlying the memory impairments induced by prolonged food deprivation.

Altered metabolic state impedes limb regeneration in salamanders.

Salamanders are unique among tetrapods in their ability to regenerate their limbs throughout life. Like other poikilothermic amphibians, salamanders also show a remarkable capacity to survive long periods of starvation. Whether the physiological reserves necessary for tissue regeneration are preserved or sacrificed in starved salamanders is unknown. In the current study, we maintained Iberian ribbed newts ( Pleurodeles waltl) under extreme physiological stress to assess the extent of regeneration and identify the molecular and cellular changes that may occur under such conditions. After 19 months of complete food deprivation, the animals exhibited extensive morphological and physiological adaptations but remained behaviorally active and vigilant. Autophagy was elevated in different tissues and the transformed gut microbiota indicated remodeling of the intestinal tract related to autophagy. Upon limb amputation in animals starved for 21 months, regeneration proceeded with progenitor cell proliferation and migration, leading to limb blastema formation. However, limb outgrowth and patterning were substantially attenuated. Blockage of autophagy inhibited cell proliferation and blastema formation in starved animals, but not in fed animals. Hence, tissue autophagy and the regenerative response were tightly coupled only when animals were under stress. Our results demonstrate that under adverse conditions, salamanders can exploit alternative strategies to secure blastema formation for limb regeneration.

Olfactory perceptual decision-making is biased by motivational state.

Growing evidence suggests that internal factors influence how we perceive the world. However, it remains unclear whether and how motivational states, such as hunger and satiety, regulate perceptual decision-making in the olfactory domain. Here, we developed a novel behavioral task involving mixtures of food and nonfood odors (i.e., cinnamon bun and cedar; pizza and pine) to assess olfactory perceptual decision-making in humans. Participants completed the task before and after eating a meal that matched one of the food odors, allowing us to compare perception of meal-matched and non-matched odors across fasted and sated states. We found that participants were less likely to perceive meal-matched, but not non-matched, odors as food dominant in the sated state. Moreover, functional magnetic resonance imaging (fMRI) data revealed neural changes that paralleled these behavioral effects. Namely, odor-evoked fMRI responses in olfactory/limbic brain regions were altered after the meal, such that neural patterns for meal-matched odor pairs were less discriminable and less food-like than their non-matched counterparts. Our findings demonstrate that olfactory perceptual decision-making is biased by motivational state in an odor-specific manner and highlight a potential brain mechanism underlying this adaptive behavior.

Microstructural changes in human ingestive behavior after Roux-en-Y gastric bypass during liquid meals.

BACKGROUNDRoux-en-Y gastric bypass (RYGB) decreases energy intake and is, therefore, an effective treatment of obesity. The behavioral bases of the decreased calorie intake remain to be elucidated. We applied the methodology of microstructural analysis of meal intake to establish the behavioral features of ingestion in an effort to discern the various controls of feeding as a function of RYGB.METHODSThe ingestive microstructure of a standardized liquid meal in a cohort of 11 RYGB patients, in 10 patients with obesity, and in 10 healthy-weight adults was prospectively assessed from baseline to 1 year with a custom-designed drinkometer. Statistics were performed on log-transformed ratios of change from baseline so that each participant served as their own control, and proportional increases and decreases were numerically symmetrical. Data-driven (3 seconds) and additional burst pause criteria (1 and 5 seconds) were used.RESULTSAt baseline, the mean meal size (909.2 versus 557.6 kCal), burst size (28.8 versus 17.6 mL), and meal duration (433 versus 381 seconds) differed between RYGB patients and healthy-weight controls, whereas suck volume (5.2 versus 4.6 mL) and number of bursts (19.7 versus 20.1) were comparable. At 1 year, the ingestive differences between the RYGB and healthy-weight groups disappeared due to significantly decreased burst size (P = 0.008) and meal duration (P = 0.034) after RYGB. The first-minute intake also decreased after RYGB (P = 0.022).CONCLUSIONRYGB induced dynamic changes in ingestive behavior over the first postoperative year. While the eating pattern of controls remained stable, RYGB patients reduced their meal size by decreasing burst size and meal duration, suggesting that increased postingestive sensibility may mediate postbariatric ingestive behavior.TRIAL REGISTRATIONNCT03747445; https://clinicaltrials.gov/ct2/show/NCT03747445.FUNDINGThis work was supported by the University of Zurich, the Swiss National Fund (32003B_182309), and the Olga Mayenfisch Foundation. Bálint File was supported by the Hungarian Brain Research Program Grant (grant no. 2017-1.2.1-NKP-2017-00002).

Chronic food restriction enhances dopamine-mediated intracranial self-stimulation.

Dopamine-mediated reinforcement and behavioral adaptation is essential to survival. Here, we test the effects of food restriction on dopamine-mediated learning and reinforcement using optical intracranial self-stimulation (oICSS), an optogenetic version of conventional electrical ICSS (also known as brain stimulation reward, BSR). Using mouse genetic lines to express channelrhodopsin selectively in midbrain dopamine neurons, we demonstrate that genetically expressed channelrhodopsin can mediate optically evoked dopamine release and support self-stimulation in a lever-pressing paradigm. Using this midbrain dopamine oICSS preparation, we compare acquisition and rate of pressing in ad libitum versus food restricted mice. Food restriction facilitated both more rapid acquisition of self-stimulation behavior and higher rates of responding; reversing food status after acquisition modulated response vigor in already established behavior. These data suggest that food restriction enhances both the acquisition and expression of dopamine-reinforced self-stimulation responding. These data demonstrate the utility of oICSS for examining changes in reinforcement learning concomitant to neuroadaptations induced in dopamine signaling by experimental manipulations such as food restriction.

Elephant seal muscle cells adapt to sustained glucocorticoid exposure by shifting their metabolic phenotype.

Elephant seals experience natural periods of prolonged food deprivation while breeding, molting, and undergoing postnatal development. Prolonged food deprivation in elephant seals increases circulating glucocorticoids without inducing muscle atrophy, but the cellular mechanisms that allow elephant seals to cope with such conditions remain elusive. We generated a cellular model and conducted transcriptomic, metabolic, and morphological analyses to study how seal cells adapt to sustained glucocorticoid exposure. Seal muscle progenitor cells differentiate into contractile myotubes with a distinctive morphology, gene expression profile, and metabolic phenotype. Exposure to dexamethasone at three ascending concentrations for 48 h modulated the expression of six clusters of genes related to structural constituents of muscle and pathways associated with energy metabolism and cell survival. Knockdown of the glucocorticoid receptor (GR) and downstream expression analyses corroborated that GR mediates the observed effects. Dexamethasone also decreased cellular respiration, shifted the metabolic phenotype toward glycolysis, and induced mitochondrial fission and dissociation of mitochondria-endoplasmic reticulum (ER) interactions without decreasing cell viability. Knockdown of DNA damage-inducible transcript 4 (DDIT4), a GR target involved in the dissociation of mitochondria-ER membranes, recovered respiration and modulated antioxidant gene expression in myotubes treated with dexamethasone. These results show that adaptation to sustained glucocorticoid exposure in elephant seal myotubes involves a metabolic shift toward glycolysis, which is supported by alterations in mitochondrial morphology and a reduction in mitochondria-ER interactions, resulting in decreased respiration without compromising cell survival.

Effects of food restriction on the conditioned reinforcing properties of an opioid-associated stimulus.

Food restriction promotes drug self-administration; however, the effects of food restriction on the conditioned reinforcing properties of drug-associated stimuli are less clear. We tested the extent to which food restriction modified the conditioned reinforcing properties of a remifentanil-associated stimulus following conditioning with 3.2 or 1.0 µg/kg/infusion of remifentanil. First, we provided restricted (20 g/day standard chow) or ad libitum access to standard chow to rats. Second, within each feeding condition, we exposed rats to 20 intravenous infusions of remifentanil and 20 stimulus presentations that were delivered response independently each day for 5 days. For the experimental group (paired Pavlovian), the remifentanil infusions and stimulus presentations were delivered concurrently. The control group (random control) received the same number of infusions and stimulus presentations, but were not paired. For 28 sessions, we tested the extent to which the stimulus functioned as a conditioned reinforcer by allowing rats to freely respond for presentations of the remifentanil-associated stimulus. Following conditioning with 3.2 µg/kg/infusion of remifentanil, we found that rats that in the Paired Pavlovian group responded for the remifentanil-associated stimulus significantly more than rats in the Random control group, regardless of feeding condition. Following conditioning with 1.0 µg/kg/infusion of remifentanil, the remifentanil-associated stimulus was not associated with conditioned reinforcing properties, regardless of feeding condition. These findings confirm previous research demonstrating that a remifentanil-associated stimulus takes on conditioned reinforcing properties in a dose-dependent manner.

Morphological Analysis of the Hindbrain Glucose Sensor-Hypothalamic Neural Pathway Activated by Hindbrain Glucoprivation.

Lowered glucose availability, sensed by the hindbrain, has been suggested to enhance gluconeogenesis and food intake as well as suppress reproductive function. In fact, our previous histological and in vitro studies suggest that hindbrain ependymal cells function as a glucose sensor. The present study aimed to clarify the hindbrain glucose sensor-hypothalamic neural pathway activated in response to hindbrain glucoprivation to mediate counterregulatory physiological responses. Administration of 2-deoxy-D-glucose (2DG), an inhibitor of glucose utilization, into the fourth ventricle (4V) of male rats for 0.5 hour induced messenger RNA (mRNA) expression of c-fos, a marker for cellular activation, in ependymal cells in the 4V, but not in the lateral ventricle, the third ventricle or the central canal without a significant change in blood glucose and testosterone levels. Administration of 2DG into the 4V for 1 hour significantly increased blood glucose levels, food intake, and decreased blood testosterone levels. Simultaneously, the expression of c-Fos protein was detected in the 4V ependymal cells; dopamine ß-hydroxylase-immunoreactive cells in the C1, C2, and A6 regions; neuropeptide Y (NPY) mRNA-positive cells in the C2; corticotropin-releasing hormone (CRH) mRNA-positive cells in the hypothalamic paraventricular nucleus (PVN); and NPY mRNA-positive cells in the arcuate nucleus (ARC). Taken together, these results suggest that lowered glucose availability, sensed by 4V ependymal cells, activates hindbrain catecholaminergic and/or NPY neurons followed by CRH neurons in the PVN and NPY neurons in the ARC, thereby leading to counterregulatory responses, such as an enhancement of gluconeogenesis, increased food intake, and suppression of sex steroid secretion.

Digging behavior discrimination test to probe burrowing and exploratory digging in male and female mice.

Digging behavior is often used to test motor function and repetitive behaviors in mice. Different digging paradigms have been developed for behaviors related to anxiety and compulsion in mouse lines generated to recapitulate genetic mutations leading to psychiatric and neurological disorders. However, the interpretation of these tests has been confounded by the difficulty of determining the motivation behind digging in mice. Digging is a naturalistic mouse behavior that can be focused toward different goals, that is foraging for food, burrowing for shelter, burying objects, or even for recreation as has been shown for dogs, ferrets, and human children. However, the interpretation of results from current testing protocols assumes the motivation behind the behavior often concluding that increased digging is a repetitive or compulsive behavior. We asked whether providing a choice between different types of digging activities would increase sensitivity to assess digging motivation. Here, we present a test to distinguish between burrowing and exploratory digging in mice. We found that mice prefer burrowing when the option is available. When food restriction was used to promote a switch from burrowing to exploration, males readily switched from burrowing to digging outside, while females did not. In addition, when we tested a model of intellectual disability and autism spectrum disorder that had shown inconsistent results in the marble burying test, the Cc2d1a conditional knockout mouse, we found greatly reduced burrowing only in males. Our findings indicate that digging is a nuanced motivated behavior and suggest that male and female rodents may perform it differently.

Nutrigenomic analyses reveal miRNAs and mRNAs affected by feed restriction in the mammary gland of midlactation dairy cows.

The objective of this study was to investigate the effects of feed restriction on mammary miRNAs and coding gene expression in midlactation cows. Five Holstein cows and 6 Montbéliarde cows underwent 6 days of feed restriction, during which feed allowance was reduced to meet 50% of their net energy for lactation requirements. Mammary biopsies were performed before and at the end of the restriction period. Mammary miRNA and mRNA analyses were performed using high-throughput sequencing and microarray analyses, respectively. Feed restriction induced a negative energy balance and decreased milk production and fat and protein yields in both breeds. Feed restriction modified the expression of 27 miRNAs and 374 mRNAs in mammary glands from Holstein cows, whereas no significant miRNA change was observed in Montbéliarde cows. Among the 27 differentially expressed miRNAs, 8 miRNAs were associated with dairy QTL. Analysis of target genes indicate that the 8 most abundantly expressed miRNAs control transcripts related to lipid metabolism, mammary remodeling and stress response. A comparison between the mRNAs targeted by the 8 most strongly expressed miRNAs and 374 differentially expressed mRNAs identified 59 mRNAs in common. The bioinformatic analyses of these 59 mRNAs revealed their implication in lipid metabolism and endothelial cell proliferation. These effects of feed restriction on mammary miRNAs and mRNAs observed in Holstein cows suggest a potential role of miRNAs in mammary structure and lipid biosynthesis that could explain changes in milk production and composition.

RNA-Seq Transcriptome Analysis of the Liver and Brain of the Black Carp (Mylopharyngodon piceus) During Fasting.

The black carp (Mylopharyngodon piceus) is an important carnivorous freshwater-cultured species. To understand the molecular basis underlying the response of black carp to fasting, we used RNA-Seq to analyze the liver and brain transcriptome of fasting fish. Annotation to the NCBI database identified 66,609 unigenes, of which 22,841 were classified into the Gene Ontology database and 15,925 were identified in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Comparative analysis of the expression profile between fasting and normal feeding fish revealed 13,737 differentially expressed genes (P < 0.05), of which 12,480 were found in liver tissue and 1257 were found in brain tissue. The KEGG pathway analysis showed significant differences in expression of genes involved in metabolic and immune pathways, such as the insulin signaling pathway, PI3K-Akt signaling pathway, cAMP signaling pathway, FoxO signaling pathway, AMPK signaling pathway, endocytosis, and apoptosis. Quantitative real-time PCR analysis confirmed that expression of the genes encoding the factors involved in those pathways differed between fasting and feeding fish. These results provide valuable information about the molecular response mechanism of black carp under fasting conditions.

Long-Term Shaping of Corticostriatal Synaptic Activity by Acute Fasting.

Food restriction is a robust nongenic, nonsurgical and nonpharmacologic intervention known to improve health and extend lifespan in various species. Food is considered the most essential and frequently consumed natural reward, and current observations have demonstrated homeostatic responses and neuroadaptations to sustained intermittent or chronic deprivation. Results obtained to date indicate that food deprivation affects glutamatergic synapses, favoring the insertion of GluA2-lacking α-Ammino-3-idrossi-5-Metil-4-idrossazol-Propionic Acid receptors (AMPARs) in postsynaptic membranes. Despite an increasing number of studies pointing towards specific changes in response to dietary restrictions in brain regions, such as the nucleus accumbens and hippocampus, none have investigated the long-term effects of such practice in the dorsal striatum. This basal ganglia nucleus is involved in habit formation and in eating behavior, especially that based on dopaminergic control of motivation for food in both humans and animals. Here, we explored whether we could retrieve long-term signs of changes in AMPARs subunit composition in dorsal striatal neurons of mice acutely deprived for 12 hours/day for two consecutive days by analyzing glutamatergic neurotransmission and the principal forms of dopamine and glutamate-dependent synaptic plasticity. Overall, our data show that a moderate food deprivation in experimental animals is a salient event mirrored by a series of neuroadaptations and suggest that dietary restriction may be determinant in shaping striatal synaptic plasticity in the physiological state.

Sulfur sequestration promotes multicellularity during nutrient limitation.

The behaviour of Dictyostelium discoideum depends on nutrients1. When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism2,3. This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species-generated as a consequence of nutrient limitation-lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron-sulfur cluster. The regulated sequestration of sulfur maintains D. discoideum in a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes.