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Current Biology : CB Jun 2022Maintaining nutrient and energy homeostasis is crucial for the survival and function of cells and organisms in response to environmental stress. Cells have evolved a... (Review)
Review
Maintaining nutrient and energy homeostasis is crucial for the survival and function of cells and organisms in response to environmental stress. Cells have evolved a stress-induced catabolic pathway, termed autophagy, to adapt to stress conditions such as starvation. During autophagy, damaged or non-essential cellular structures are broken down in lysosomes, and the resulting metabolites are reused for core biosynthetic processes or energy production. Recent studies have revealed that autophagy can target and degrade different types of nutrient stores and produce a variety of metabolites and fuels, including amino acids, nucleotides, lipids and carbohydrates. Here, we will focus on how autophagy functions to balance cellular nutrient and energy demand and supply - specifically, how energy deprivation switches on autophagic catabolism, how autophagy halts anabolism by degrading the protein synthesis machinery, and how bulk and selective autophagy-derived metabolites recycle and feed into a variety of bioenergetic and anabolic pathways during stress conditions. Recent new insights and progress in these areas provide a better understanding of how resource mobilization and reallocation sustain essential metabolic and anabolic activities under unfavorable conditions.
Topics: Autophagy; Energy Metabolism; Humans; Lysosomes; Nutrients; Starvation
PubMed: 35728554
DOI: 10.1016/j.cub.2022.04.071 -
The Journal of Biological Chemistry Apr 2018Autophagy is a highly conserved process and is essential for the maintenance of cellular homeostasis. Autophagy occurs at a basal level in all cells, but it can be... (Review)
Review
Autophagy is a highly conserved process and is essential for the maintenance of cellular homeostasis. Autophagy occurs at a basal level in all cells, but it can be up-regulated during stress, starvation, or infection. Misregulation of autophagy has been linked to various disorders, including cancer, neurodegeneration, and immune diseases. Here, we discuss the essential proteins acting in the formation of an autophagosome, with a focus on the ULK and VPS34 kinase complexes, phosphatidylinositol 3-phosphate effector proteins, and the transmembrane autophagy-related protein ATG9. The function and regulation of these and other autophagy-related proteins acting during formation will be addressed, in particular during amino acid starvation.
Topics: Animals; Autophagy; Autophagy-Related Protein-1 Homolog; Autophagy-Related Proteins; Class III Phosphatidylinositol 3-Kinases; Humans; Immune System Diseases; Infections; Neoplasm Proteins; Neoplasms; Neurodegenerative Diseases; Starvation
PubMed: 29371398
DOI: 10.1074/jbc.R117.810366 -
Journal of Lipid Research Oct 2014Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free... (Review)
Review
Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value.
Topics: Adenosine Triphosphate; Diet, Ketogenic; Esters; Fatty Acids; Humans; Ketones; Ketosis; NAD; Starvation; Ubiquinone
PubMed: 24714648
DOI: 10.1194/jlr.R046292 -
Clinical Medicine (London, England) 2004Nutrition and fluid and electrolyte balance are inextricably linked through ingestion, digestion, absorption and intermediary metabolism. Studies are described showing... (Review)
Review
Nutrition and fluid and electrolyte balance are inextricably linked through ingestion, digestion, absorption and intermediary metabolism. Studies are described showing that man's physiological capacity to excrete excess salt and water is limited under normal conditions; it is further reduced by starvation and injury, so that patients are easily overloaded, resulting in increased complications of illness and surgery. Return of gastrointestinal function postoperatively is delayed by moderate saline overload. Illness not only influences external fluid and electrolyte balance but also internal balance between the extracellular and intracellular spaces and between the intravascular and extravascular components of the extracellular space. The mechanisms and management of these changes are discussed. The importance of fluid and electrolyte balance in nutritional support is emphasised--indeed, the benefits of nutrition may be negated by electrolyte imbalance. The relationships between serum albumin concentration, illness, nutrition and fluid balance are discussed and the limited role of albumin infusions described. Surveys among doctors have revealed a poor knowledge of fluid and electrolyte balance. Measures are needed to improve training.
Topics: Clinical Competence; Edema; Humans; Intestinal Absorption; Nutritional Physiological Phenomena; Starvation; Water-Electrolyte Balance; Water-Electrolyte Imbalance; Wounds and Injuries
PubMed: 15656483
DOI: 10.7861/clinmedicine.4-6-573 -
Scientific Reports Aug 2021The effects of feeding and starvation have been studied with respect to oxidative stress and enzymatic antioxidant activities in the whole body of 4 cm rainbow trout...
The effects of feeding and starvation have been studied with respect to oxidative stress and enzymatic antioxidant activities in the whole body of 4 cm rainbow trout fry Oncorhynchus mykiss (Walbaum 1792). The experiment was conducted for 28 days. The selected biomarkers for the study were determined, including non-enzymic scavengers glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde (MDA) contents and a number of enzymes are known to have major antioxidant activity, such as activities of süperoksit dismutaz (SOD), catalase (CAT), glutatyon peroksidaz (GSHpx), glutatyon Redüktaz (GR) and Glutatyon-S-Transferaz (GST). There is an endogenous cellular glutathione pool which consists of two forms of glutathione, i.e. the GSH and the GSSG. Oxidative damage was measured by the formation of MDA as an indication of lipid peroxidation. The activities of SOD in 14th and 28th day and the activity of CAT in 14th day were increased significantly during the 28 days of starvation. GSHpx and GR activities in starved fry decreased significantly in 28th day. GST activity in all starved fry showed the most significant increases the period of 28 days starving. The highest ΣSFA (Total Saturated Fatty Acid) content was obtained from 28 day starved fry. In starved fry, there was an apparent preference in utilization of C18:1n-9 than in the fed fry. In both starved and fed fry, C16:1n-7 was preferentially kept during the same period. Fry kept 28 days under starvation conditions exhausted C15:0, C17:0, C18:3n-6, C22:0, C24:0. They utilized less C20:5n-3 acid and conserved strongly C22:6n-3 acid. Concentrations of C20:5n-3, C22:5n-3, C22:6n-3 and total n-3 fatty acids significantly increased and C18:3n-3 significantly decreased in the whole body of starved fry during starvation period. A significant increase in the concentrations of C22:5n-3 and C22:6n-3 was determined in the fed fries in the last 2 weeks. Fat-soluble vitamins, cholesterol, stigmasterol and β-sitosterol levels were also determined in the same period of O. mykiss fry.
Topics: Animal Feed; Animals; Antioxidants; Eating; Fatty Acids; Lipid Peroxidation; Oncorhynchus mykiss; Oxidoreductases; Starvation
PubMed: 34408240
DOI: 10.1038/s41598-021-96204-y -
Maturitas Apr 2016Methods of identifying malnutrition in the rehabilitation setting require further examination so that patient outcomes may be improved. The purpose of this narrative... (Review)
Review
Methods of identifying malnutrition in the rehabilitation setting require further examination so that patient outcomes may be improved. The purpose of this narrative review was to: (1) examine the defining characteristics of malnutrition, starvation, sarcopenia and cachexia; (2) review the validity of nutrition screening tools and nutrition assessment tools in the rehabilitation setting; and (3) determine the prevalence of malnutrition in the rehabilitation setting by geographical region and method of diagnosis. A narrative review was conducted drawing upon international literature. Starvation represents one form of malnutrition. Inadequate energy and protein intake are the critical factor in the aetiology of malnutrition, which is distinct from sarcopenia and cachexia. Eight nutrition screening tools and two nutrition assessment tools have been evaluated for criterion validity in the rehabilitation setting, and consideration must be given to the resources of the facility and the patient group in order to select the appropriate tool. The prevalence of malnutrition in the rehabilitation setting ranges from 14-65% worldwide with the highest prevalence reported in rural, European and Australian settings. Malnutrition is highly prevalent in the rehabilitation setting, and consideration must be given to the patient group when determining the most appropriate method of identification so that resources may be used efficaciously and the chance of misdiagnosis minimised.
Topics: Australia; Cachexia; Europe; Humans; Nutrition Assessment; Nutritional Status; Prevalence; Protein-Energy Malnutrition; Rehabilitation; Rural Population; Sarcopenia; Starvation
PubMed: 26921933
DOI: 10.1016/j.maturitas.2016.01.014 -
Nature Metabolism Feb 2022During starvation, mammalian brains can adapt their metabolism, switching from glucose to alternative peripheral fuel sources. In the Drosophila starved brain, memory...
During starvation, mammalian brains can adapt their metabolism, switching from glucose to alternative peripheral fuel sources. In the Drosophila starved brain, memory formation is subject to adaptative plasticity, but whether this adaptive plasticity relies on metabolic adaptation remains unclear. Here we show that during starvation, neurons of the fly olfactory memory centre import and use ketone bodies (KBs) as an energy substrate to sustain aversive memory formation. We identify local providers within the brain, the cortex glia, that use their own lipid store to synthesize KBs before exporting them to neurons via monocarboxylate transporters. Finally, we show that the master energy sensor AMP-activated protein kinase regulates both lipid mobilization and KB export in cortex glia. Our data provide a general schema of the metabolic interactions within the brain to support memory when glucose is scarce.
Topics: Animals; Drosophila; Glucose; Ketone Bodies; Mammals; Neuroglia; Neurons; Starvation
PubMed: 35177854
DOI: 10.1038/s42255-022-00528-6 -
Nutrients Jul 2020Severely undernourished and underweight anorexia nervosa (AN) patients typically remain active and mobile. Might such persistent physical activity in AN be supported by... (Review)
Review
Might Starvation-Induced Adaptations in Muscle Mass, Muscle Morphology and Muscle Function Contribute to the Increased Urge for Movement and to Spontaneous Physical Activity in Anorexia Nervosa?
Severely undernourished and underweight anorexia nervosa (AN) patients typically remain active and mobile. Might such persistent physical activity in AN be supported by specific adaptations in muscle tissue during long term undernutrition? To identify potential differences, studies examining the effects of undernutrition on skeletal muscle mass, muscle morphology and muscle function in healthy humans and in AN patients were reviewed. Adjustments in muscle morphology and function in AN did not differ in substance from those in healthy humans, undernourished people, or undergoing semi-starvation. Loss of muscle mass, changes in muscle contractility and atrophy of muscle fibers (predominantly type II fibers) characterized both groups. Muscle innervation was unaffected. Work capacity in men in semi-starvation experiments and in females with AN declined by about 70% and 50%, respectively. Perceptions of fatigue and effort distinguished the groups: signs of general weakness, tiring quickly and avoidance of physical activity that were recorded in semi-starvation were not reported for AN patients. The absence of distinctive starvation-related adjustments in skeletal muscle in AN suggests that new methods, such as muscle gene expression profiles in response to deficient nutrient intake, and better knowledge of the central regulatory circuitries contributing to motor urgency will be required to shed light on the persistent mobility in AN patients.
Topics: Adaptation, Physiological; Adult; Anorexia Nervosa; Energy Intake; Exercise; Female; Humans; Male; Malnutrition; Movement; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Psychomotor Agitation; Starvation; Young Adult
PubMed: 32664448
DOI: 10.3390/nu12072060 -
Nature Communications Oct 2021RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal...
RIPK1 is a crucial regulator of cell death and survival. Ripk1 deficiency promotes mouse survival in the prenatal period while inhibits survival in the early postnatal period without a clear mechanism. Metabolism regulation and autophagy are critical to neonatal survival from severe starvation at birth. However, the mechanism by which RIPK1 regulates starvation resistance and survival remains unclear. Here, we address this question by discovering the metabolic regulatory role of RIPK1. First, metabolomics analysis reveals that Ripk1 deficiency specifically increases aspartate levels in both mouse neonates and mammalian cells under starvation conditions. Increased aspartate in Ripk1 cells enhances the TCA flux and ATP production. The energy imbalance causes defective autophagy induction by inhibiting the AMPK/ULK1 pathway. Transcriptional analyses demonstrate that Ripk1 deficiency downregulates gene expression in aspartate catabolism by inactivating SP1. To summarize, this study reveals that RIPK1 serves as a metabolic regulator responsible for starvation resistance.
Topics: AMP-Activated Protein Kinases; Adenosine Triphosphate; Animals; Animals, Newborn; Aspartic Acid; Autophagy; Autophagy-Related Protein-1 Homolog; Cell Line; Cell Nucleus; Cell Survival; Citric Acid Cycle; Humans; Metabolomics; Mice; Receptor-Interacting Protein Serine-Threonine Kinases; Signal Transduction; Sp1 Transcription Factor; Starvation
PubMed: 34686667
DOI: 10.1038/s41467-021-26423-4 -
Nature Aging Sep 2023Dietary restriction promotes longevity in several species via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Here using the...
Dietary restriction promotes longevity in several species via autophagy activation. However, changes to lysosomes underlying this effect remain unclear. Here using the nematode Caenorhabditis elegans, we show that the induction of autophagic tubular lysosomes (TLs), which occurs upon dietary restriction or mechanistic target of rapamycin inhibition, is a critical event linking reduced food intake to lifespan extension. We find that starvation induces TLs not only in affected individuals but also in well-fed descendants, and the presence of gut TLs in well-fed progeny is predictive of enhanced lifespan. Furthermore, we demonstrate that expression of Drosophila small VCP-interacting protein, a TL activator in flies, artificially induces TLs in well-fed worms and improves C. elegans health in old age. These findings identify TLs as a new class of lysosomes that couples starvation to healthy aging.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Healthy Aging; Starvation; Lysosomes
PubMed: 37580394
DOI: 10.1038/s43587-023-00470-6