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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The scientific study of obesity has been dominated throughout the twentieth century by the concept of energy balance. This conceptual approach, based on fundamental thermodynamic principles, states that energy cannot be destroyed, and can only be gained, lost or stored by an organism. Its application in obesity research has emphasised excessive appetite (gluttony), or insufficient physical activity (sloth), as the primary determinants of excess weight gain, reflected in current guidelines for obesity prevention and treatment. This model cannot explain why weight accumulates persistently rather than reaching a plateau, and underplays the effect of variability in dietary constituents on energy and intermediary metabolism. An alternative model emphasises the capacity of fructose and fructose-derived sweeteners (sucrose, high-fructose corn syrup) to perturb cellular metabolism via modification of the adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio, activation of AMP kinase and compensatory mechanisms, which favour adipose tissue accretion and increased appetite while depressing physical activity. This conceptual model implicates chronic hyperinsulinaemia in the presence of a paradoxical state of 'cellular starvation' as a key driver of the metabolic modifications inducing chronic weight gain. We combine evidence from in vitro and in vivo experiments to formulate a perspective on obesity aetiology that emphasises metabolic flexibility and dietary composition rather than energy balance. Using this model, we question the direction of causation of reported associations between obesity and sleep duration or childhood growth. Our perspective generates new hypotheses, which can be tested to improve our understanding of the current obesity epidemic, and to identify novel strategies for prevention or treatment.
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PMID:Obesity and energy balance: is the tail wagging the dog? 2177 13

Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions, including modulation of wound healing and inflammation. Hypothalamic PGRN has been implicated in the development of sexual dimorphism. In the present study, a potential role for PGRN in the hypothalamic regulation of appetite and body weight was investigated. In adult rodents, PGRN was highly expressed in periventricular tanycytes and in hypothalamic neurons, which are known to contain glucose-sensing machinery. Hypothalamic PGRN expression levels were decreased under low-energy conditions (starvation and 2-deoxy-D-glucose administration) but increased under high-energy condition (postprandially). Intracerebrovetricular administration of PGRN significantly suppressed nocturnal feeding as well as hyperphagia induced by 2-deoxyglucose, neuropeptide Y, and Agouti-related peptide. Moreover, the inhibition of hypothalamic PGRN expression or action increased food intake and promoted weight gain, suggesting that endogenous PGRN functions as an appetite suppressor in the hypothalamus. Investigation of the mechanism of action revealed that PGRN diminished orexigenic neuropeptide Y and Agouti-related peptide production but stimulated anorexigenic proopiomelanocortin production, at least in part through the regulation of hypothalamic AMP-activated protein kinase. Notably, PGRN was also expressed in hypothalamic microglia. In diet-induced obese mice, microglial PGRN expression was increased, and the anorectic response to PGRN was blunted. These findings highlight a physiological role for PGRN in hypothalamic glucose-sensing and appetite regulation. Alterations in hypothalamic PGRN production or action may be linked to appetite dysregulation in obesity.
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PMID:Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. 2193 69

Dieting makes you fat - the title of a book published in 1983 - embodies the notion that dieting to control body weight predisposes the individual to acquire even more body fat. While this notion is controversial, its debate underscores the large gap that exists in our understanding of basic physiological laws that govern the regulation of human body composition. A striking example is the key role attributed to adipokines as feedback signals between adipose tissue depletion and compensatory increases in food intake. Yet, the relative importance of fat depletion per se as a determinant of post-dieting hyperphagia is unknown. On the other hand, the question of whether the depletion of lean tissues can provide feedback signals on the hunger-appetite drive is rarely invoked, despite evidence that food intake during growth is dominated by the impetus for lean tissue deposition, amidst proposals for the existence of protein-static mechanisms for the regulation of growth and maintenance of lean body mass. In fact, a feedback loop between fat depletion and food intake cannot explain why human subjects recovering from starvation continue to overeat well after body fat has been restored to pre-starvation values, thereby contributing to 'fat overshooting'. In addressing the plausibility and mechanistic basis by which dieting may predispose to increased fatness, this paper integrates the results derived from re-analysis of classic longitudinal studies of human starvation and refeeding. These suggest that feedback signals from both fat and lean tissues contribute to recovering body weight through effects on energy intake and thermogenesis, and that a faster rate of fat recovery relative to lean tissue recovery is a central outcome of body composition autoregulation that drives fat overshooting. A main implication of these findings is that the risk of becoming fatter in response to dieting is greater in lean than in obese individuals.
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PMID:How dieting makes some fatter: from a perspective of human body composition autoregulation. 2247 74

Hunger is a complex behavioural state that elicits intense food seeking and consumption. These behaviours are rapidly recapitulated by activation of starvation-sensitive AGRP neurons, which present an entry point for reverse-engineering neural circuits for hunger. Here we mapped synaptic interactions of AGRP neurons with multiple cell populations in mice and probed the contribution of these distinct circuits to feeding behaviour using optogenetic and pharmacogenetic techniques. An inhibitory circuit with paraventricular hypothalamus (PVH) neurons substantially accounted for acute AGRP neuron-evoked eating, whereas two other prominent circuits were insufficient. Within the PVH, we found that AGRP neurons target and inhibit oxytocin neurons, a small population that is selectively lost in Prader-Willi syndrome, a condition involving insatiable hunger. By developing strategies for evaluating molecularly defined circuits, we show that AGRP neuron suppression of oxytocin neurons is critical for evoked feeding. These experiments reveal a new neural circuit that regulates hunger state and pathways associated with overeating disorders.
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PMID:Deconstruction of a neural circuit for hunger. 2280 96

Is starvation in anorexia nervosa (AN) or overeating in bulimia nervosa (BN) a form of addiction? Alternatively, why are individuals with BN more vulnerable and individuals with AN protected from substance abuse? Such questions have been generated by recent studies suggesting that there are overlapping neural circuits for foods and drugs of abuse. To determine whether a shared neurobiology contributes to eating disorders and substance abuse, this review focused on imaging studies that investigated response to tastes of food and tasks designed to characterize reward and behavioral inhibition in AN and BN. BN and those with substance abuse disorders may share dopamine D2 receptor-related vulnerabilities, and opposite findings may contribute to "protection" from substance abuse in AN. Moreover, imaging studies provide insights into executive corticostriatal processes related to extraordinary inhibition and self-control in AN and diminished inhibitory self-control in BN that may influence the rewarding aspect of palatable foods and likely other consummatory behaviors. AN and BN tend to have premorbid traits, such as perfectionism and anxiety that make them vulnerable to using extremes of food ingestion, which serve to reduce negative mood states. Dysregulation within and/or between limbic and executive corticostriatal circuits contributes to such symptoms. Limited data support the hypothesis that reward and inhibitory processes may contribute to symptoms in eating disorders and addictive disorders, but little is known about the molecular biology of such mechanisms in terms of shared or independent processes.
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PMID:Does a shared neurobiology for foods and drugs of abuse contribute to extremes of food ingestion in anorexia and bulimia nervosa? 2338 Jul 16

Diabetic ketoacidosis is characterized by a serum glucose level greater than 250 mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L, an elevated serum ketone level, and dehydration. Insulin deficiency is the main precipitating factor. Diabetic ketoacidosis can occur in persons of all ages, with 14 percent of cases occurring in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. The case fatality rate is 1 to 5 percent. About one-third of all cases are in persons without a history of diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent), weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitrogen, creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood count; urinalysis; electrocardiography; and calculation of anion gap and osmolar gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and can assist in diagnosing comorbid conditions. Appropriate treatment includes administering intravenous fluids and insulin, and monitoring glucose and electrolyte levels. Cerebral edema is a rare but severe complication that occurs predominantly in children. Physicians should recognize the signs of diabetic ketoacidosis for prompt diagnosis, and identify early symptoms to prevent it. Patient education should include information on how to adjust insulin during times of illness and how to monitor glucose and ketone levels, as well as information on the importance of medication compliance.
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PMID:Diabetic ketoacidosis: evaluation and treatment. 2354 50

How have climate change and diet shaped the evolution of human energy metabolism, and responses to vitamin C, fructose and uric acid? Through the last three millennia observant physicians have noted the association of inappropriate diets with increased incidence of obesity, heart disease, diabetes and cancer, and over the past 300 years doctors in the UK observed that overeating increased the incidence of these diseases. Anthropological studies of the Inuit culture in the mid-nineteenth century revealed that humans can survive and thrive in the virtual absence of dietary carbohydrate. In the 1960s, Cahill revealed the flexibility of human metabolism in response to partial and total starvation and demonstrated that type 2 diabetics were better adapted than healthy subjects to conserving protein during fasting. The potential role for brown adipose tissue thermogenesis in temperature maintenance and dietary calorie control was suggested by Rothwell and Stock from their experiments with 'cafeteria fed rats' in the 1980s. Recent advances in gene array studies and PET scanning support a role for this process in humans. The industrialisation of food processing in the twentieth century has led to increases in palatability and digestibility with a parallel loss of quality leading to overconsumption and the current obesity epidemic. The switch from animal to vegetable fats at the beginning of the twentieth century, followed by the rapid increase in sugar and fructose consumption from 1979 is mirrored by a steep increase in obesity in the 1980s, in the UK and USA. Containment of the obesity epidemic is compounded by the addictive properties of sugar which involve the same dopamine receptors in the pleasure centres of the brain as for cocaine, nicotine and alcohol. Of the many other toxic effects of excessive sugar consumption, immunocompromisation, kidney damage, atherosclerosis, oxidative stress and cancer are highlighted. The WHO and guidelines on sugar consumption include: alternative non-sugar sweeteners; toxic side-effects of aspartame. Stevia and xylitol as healthy sugar replacements; the role of food processing in dietary health; and beneficial effects of resistant starch in natural and processed foods. The rise of maize and soya-based vegetable oils have led to omega-6 fat overload and imbalance in the dietary ratio of omega-3 to omega-6 fats. This has led to toxicity studies with industrial trans fats; investigations on health risks associated with stress and comfort eating; and abdominal obesity. Other factors to consider are: diet, cholesterol and oxidative stress, as well as the new approaches to the chronology of eating and the health benefits of intermittent fasting.
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PMID:Averting comfortable lifestyle crises. 2454 68

The central nervous system (CNS) controls food intake and energy expenditure via tight coordinations between multiple neuronal populations. Specifically, two distinct neuronal populations exist in the arcuate nucleus of hypothalamus (ARH): the anorexigenic (appetite-suppressing) pro-opiomelanocortin (POMC) neurons and the orexigenic (appetite-increasing) neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. The coordinated regulation of neuronal circuit involving these neurons is essential in properly maintaining energy balance, and any disturbance therein may result in hyperphagia/obesity or hypophagia/starvation. Thus, adequate knowledge of the POMC and NPY/AgRP neuron physiology is mandatory to understand the pathophysiology of obesity and related metabolic diseases. This review will discuss the history and recent updates on the POMC and NPY/AgRP neuronal circuits, as well as the general anorexigenic and orexigenic circuits in the CNS.
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PMID:Network of hypothalamic neurons that control appetite. 2556 Jun 96

Prader-Willi syndrome (PWS) is a multifaceted developmental disorder most commonly associated with extreme hyperphagia and life-threatening obesity. PWS is a genetic disorder of imprinting with almost all cases occurring spontaneously. Behavioural and imaging studies have shown that obesity in PWS arises from overeating driven by a faulty satiety mechanism which manifests as an almost permanent state similar to starvation. With no available treatments, management of the eating behaviour is the only option and has two main strategies: restrict access to food and distract thoughts from food. In this mini review, which we have aimed at clinicians, we outline the main aspects of PWS including genetics, development of the eating behaviour and best practice approaches to management.
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PMID:A short clinical overview of Prader-Willi syndrome. 2558 8

Qualitative methodology was used to investigate the intergenerational impact of the 1932-1933 Holodomor genocide on three generations in 15 Ukrainian families. Each family, residing in Ukraine, consisted of a first generation survivor, a second generation adult child and a third generation adult grandchild of the same line. The findings show that the Holodomor, a genocide that claimed millions of lives by forced starvation, still exerts substantial effects on generations born decades later. Specifically, thematic analysis of the 45 semi-structured, in-depth interviews, done between July and November 2010, revealed that a constellation of emotions, inner states and trauma-based coping strategies emerged in the survivors during the genocide period and were subsequently transmitted into the second and third generations. This constellation, summarized by participants as living in "survival mode," included horror, fear, mistrust, sadness, shame, anger, stress and anxiety, decreased self-worth, stockpiling of food, reverence for food, overemphasis on food and overeating, inability to discard unneeded items, an indifference toward others, social hostility and risky health behaviours. Since both the family and community-society were found to be involved in trauma transmission, the findings highlight the importance of multi-framework approaches for studying and healing collective trauma.
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PMID:Living in "survival mode:" Intergenerational transmission of trauma from the Holodomor genocide of 1932-1933 in Ukraine. 2593 Dec 87


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