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American Journal of Nephrology 2021The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the... (Review)
Review
BACKGROUND
The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the clinician better insight into many clinical conditions characterized by ketoacidosis.
SUMMARY
The body adapts to long-term fasting by conserving nitrogen, as the brain increasingly utilizes keto acids, sparing the need for glucose. This shift in fuel utilization decreases the need for mobilization of amino acids from the muscle for purposes of gluconeogenesis. Loss of urinary nitrogen is initially in the form of urea when hepatic gluconeogenesis is dominant and later as ammonia reflecting increased glutamine uptake by the kidney. The carbon skeleton of glutamine is utilized for glucose production and regeneration of consumed HCO3-. The replacement of urea with NH4+ provides the osmoles needed for urine flow and waste product excretion. Over time, the urinary loss of nitrogen is minimized as kidney uptake of filtered ketone bodies becomes more complete. Adjustments in urine Na+ serve to minimize kidney K+ wasting and, along with changes in urine pH, minimize the likelihood of uric acid precipitation. There is a sexual dimorphism in response to starvation. Key Message: Ketoacidosis is a major feature of common clinical conditions to include diabetic ketoacidosis, alcoholic ketoacidosis, salicylate intoxication, SGLT2 inhibitor therapy, and calorie sufficient but carbohydrate-restricted diets. Familiarity with the pathophysiology and metabolic consequences of ketogenesis is critical, given the potential for the clinician to encounter one of these conditions.
Topics: Adaptation, Physiological; Gluconeogenesis; Glucose; Glycogenolysis; Homeostasis; Humans; Ketone Bodies; Ketosis; Kidney; Natriuresis; Potassium; Proteins; Sex Factors; Starvation; Uric Acid
PubMed: 34350876
DOI: 10.1159/000517305 -
ELife Feb 2024Experiments involving periodic stimuli shed light on the interplay between hyper-osmotic stress and glucose starvation in yeast cells.
Experiments involving periodic stimuli shed light on the interplay between hyper-osmotic stress and glucose starvation in yeast cells.
Topics: Humans; Glucose; Osmotic Pressure; Saccharomyces cerevisiae; Starvation
PubMed: 38416131
DOI: 10.7554/eLife.91717 -
The Journal of Clinical Investigation Dec 2016Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This... (Review)
Review
Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients. Leptin acts on neurons in the hypothalamus and elsewhere to elicit its effects, and mutations that affect the function of this neural circuit cause Mendelian forms of obesity. Leptin levels fall during starvation and elicit adaptive responses in many other physiologic systems, the net effect of which is to reduce energy expenditure. These effects include cessation of menstruation, insulin resistance, alterations of immune function, and neuroendocrine dysfunction, among others. Some or all of these effects are also seen in patients with constitutively low leptin levels, such as occur in lipodystrophy. Leptin is an approved treatment for generalized lipodystrophy, a condition associated with severe metabolic disease, and has also shown potential for the treatment of other types of diabetes. In addition, leptin restores reproductive capacity and increases bone mineral density in patients with hypothalamic amenorrhea, an infertility syndrome in females. Most obese patients have high endogenous levels of leptin, in some instances as a result of mutations in the neural circuit on which leptin acts, though in most cases, the pathogenesis of leptin resistance is not known. Obese patients with leptin resistance show a variable response to exogenous leptin but may respond to a combination of leptin plus amylin. Overall, the identification of leptin has provided a framework for studying the pathogenesis of obesity in the general population, clarified the nature of the biologic response to starvation, and helped to advance our understanding of the neural mechanisms that control feeding.
Topics: Adipose Tissue; Animals; Diabetes Mellitus; Humans; Hypothalamus; Leptin; Lipodystrophy; Mice; Neurons; Obesity; Receptors, Leptin; Starvation
PubMed: 27906690
DOI: 10.1172/JCI91578 -
The Journal of Nutrition Jun 2005During World War II, 36 conscientious objectors participated in a study of human starvation conducted by Ancel Keys and his colleagues at the University of Minnesota....
During World War II, 36 conscientious objectors participated in a study of human starvation conducted by Ancel Keys and his colleagues at the University of Minnesota. The Minnesota Starvation Experiment, as it was later known, was a grueling study meant to gain insight into the physical and psychologic effects of semistarvation and the problem of refeeding civilians who had been starved during the war. During the experiment, the participants were subjected to semistarvation in which most lost >25% of their weight, and many experienced anemia, fatigue, apathy, extreme weakness, irritability, neurological deficits, and lower extremity edema. In 2003-2004, 18 of the original 36 participants were still alive and were interviewed. Many came from the Historic Peace Churches (Mennonite, Brethren, and Quaker), and all expressed strong convictions about nonviolence and wanting to make a meaningful contribution during the war. Despite ethical issues about subjecting healthy humans to starvation, the men interviewed were unanimous in saying that they would do it all over again, even after knowing the suffering that they had experienced. After the experiment ended, many of the participants went on to rebuilding war-torn Europe, working in the ministries, diplomatic careers, and other activities related to nonviolence.
Topics: History, 20th Century; Human Experimentation; Humans; Minnesota; Religion; Starvation; World War II
PubMed: 15930436
DOI: 10.1093/jn/135.6.1347 -
Proceedings of the National Academy of... Nov 2008Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms...
Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.
Topics: Adult; Birth Weight; DNA Methylation; Epigenesis, Genetic; Female; Humans; Insulin-Like Growth Factor II; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Starvation
PubMed: 18955703
DOI: 10.1073/pnas.0806560105 -
Revista Espanola de Sanidad... 2018
Topics: Dissent and Disputes; Humans; Male; Prisoners; Self-Injurious Behavior; Spain; Starvation
PubMed: 29641746
DOI: No ID Found -
Journal of Veterinary Diagnostic... Jan 2022A muskox neonate () that died of starvation was diagnosed with congenital lenticular anomalies that included spherophakia and hypermature cataract associated with...
A muskox neonate () that died of starvation was diagnosed with congenital lenticular anomalies that included spherophakia and hypermature cataract associated with probable lens-induced lymphocytic uveitis and neutrophilic keratitis. Impaired sight as a result of cataract and associated inflammation likely contributed to abandonment and starvation, although maternal death cannot be excluded definitively. Ocular lesions, such as congenital cataracts and spherophakia in neonates, may be important factors affecting survival in free-ranging animals.
Topics: Animals; Canada; Cataract; Northwest Territories; Ruminants; Starvation
PubMed: 34763579
DOI: 10.1177/10406387211057470 -
American Journal of Human Biology : the... 2011Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in... (Review)
Review
Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. This review considers several possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? These possibilities are evaluated in terms of the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance.
Topics: Adaptation, Physiological; Adipogenesis; Adipose Tissue; Animals; Bone Marrow; Humans; Models, Biological; Osteogenesis; Osteoporosis; Starvation
PubMed: 21793093
DOI: 10.1002/ajhb.21202 -
BMJ (Clinical Research Ed.) Apr 2004
Topics: Humans; Insulin; Insulin Secretion; Nutrition Disorders; Phosphates; Starvation; Syndrome
PubMed: 15087326
DOI: 10.1136/bmj.328.7445.908 -
Autophagy 2018Although ribophagy was demonstrated in budding yeast a decade ago, a specific receptor for this process has been unknown. Recently, a study revealed that NUFIP1 (nuclear...
Although ribophagy was demonstrated in budding yeast a decade ago, a specific receptor for this process has been unknown. Recently, a study revealed that NUFIP1 (nuclear FMR1 interacting protein 1) functions as a receptor for the selective degradation of ribosomes by starvation-induced autophagy in cultured mammalian cells. In addition to the identification of a selective autophagy receptor, this study suggests a strategy that can be adapted to the identification of additional novel receptor proteins.
Topics: Animals; Autophagy; Receptors, Cytoplasmic and Nuclear; Ribosomes; Starvation
PubMed: 30067425
DOI: 10.1080/15548627.2018.1483672