Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of metabolic/molecular changes in obese adipose tissue considerably contribute to the pathophysiology of life style-related diseases. Fat cell-derived hormone leptin controls appetite and energy homeostasis, thereby enhancing whole body insulin sensitivity. However, clinical application of leptin for the treatment of obesity/metabolic syndrome has been hampered by the fact that leptin does not fully exert its beneficial metabolic impact on prevalent forms of obesity. In an attempt to elucidate underlying mechanism of leptin resistance in obesity, we found that the activity of skeletal muscle AMP-activated protein kinase (AMPK) tightly parallels hypothalamic leptin sensitivity and metabolic phenotype in transgenic mice overexpressing leptin. Actually, intracerebroventricular administration of melanocortin agonist MT-II robustly overcomes high fat diet-induced leptin resistance and ameliorates fuel dyshomeostasis and hyperphagia in mice, with a concomitant recovery of AMPK activity in skeletal muscle, thereby highlighting the system as a therapeutic target for leptin resistance. In this context, type 4 melanocortin receptor is a promising drug target for the treatment of obesity/metabolic syndrome.
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PMID:[Energy homeostasis regulated by an adipocyte-derived hormone--mechanism of leptin resistance and role of hypothalamic melanocortin signaling]. 1920 1

We prospectively studied the effects of fast food-based hyperalimentation on insulin sensitivity and components of the metabolic syndrome and analyzed this with respect to sex. Twelve nonobese men and 6 nonobese women (26 +/- 6.6 years old), and an age-matched control group were recruited. Subjects in the intervention group aimed for 5% to 15% weight increase by doubling their regular caloric intake based on at least 2 fast food meals a day while also adopting a sedentary lifestyle for 4 weeks (<5000 steps a day). Weight of subjects in the intervention group increased from 67.6 +/- 9.1 to 74.0 +/- 11 kg (P < .001), with no sex difference with regard to this or with respect to changes of total abdominal fat volumes or waist circumferences. Fasting insulin (men: before, 3.8 +/- 1.7 microU/mL; after, 7.4 +/- 3.1 microU/mL; P = .004; women: before, 4.9 +/- 2.3 microU/mL; after, 5.9 +/- 2.8 microU/mL; P = .17), systolic blood pressure (men: before, 117 +/- 13 mm Hg; after, 127 +/- 9.1 mm Hg; P = .002; women: before, 102 +/- 5.1 mm Hg; after, 98 +/- 5.4 mm Hg; P = .39), serum low-density lipoprotein cholesterol, and apolipoprotein B increased only in the men of the intervention group. The sex differences in the metabolic responses to the intervention were linked to a considerable difference in the fat accumulation pattern; 41.4% +/- 9.2% of the increase of the fat volume in the abdominal region was accumulated intraabdominally in men and 22.7 +/- 6.5% in women (P < .0001). This study thus showed that women are protected, compared with men, against developing intraabdominal obesity when adopting a standardized obesity-provoking lifestyle. Our findings suggest that it is not different lifestyles and/or behaviors that underlie the fact that men have a higher cardiovascular risk at the same level of percentage of body fat than women.
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PMID:Men develop more intraabdominal obesity and signs of the metabolic syndrome after hyperalimentation than women. 1939 60

Postnatal early overnutrition (EO) is a risk factor for obesity in adult life. Rats raised in a small litter can develop hyperinsulinaemia, hyperphagia, hyperleptinaemia and hypertension as adults. Since leptin regulates the hypothalamic-pituitary-thyroid axis and the metabolism of thyroid hormones, we studied the leptin signalling pathway in pituitary and thyroid glands of the postnatal EO model. To induce EO, at the third day of lactation the litter size was reduced to three pups per litter (SL group). In control litters (NL group), the litter size was adjusted to 10 pups per litter. Body weight and food intake were monitored. Rat offspring were killed at 21 (weaning) and 180 days old (adulthood). Plasma thyroid hormones, thyroid-stimulating hormone (TSH) and leptin were measured by radioimmunoassay. Proteins of the leptin signalling pathway were analysed by Western blotting. Body weight of offspring in the SL group was higher from the seventh day of lactation (+33%, P < 0.05) until 180 days old (+18%, P < 0.05). Offspring in the SL group showed higher visceral fat mass at 21 and 180 days old (+176 and +52%, respectively, P < 0.05), but plasma leptin was higher only at 21 days (+88%, P < 0.05). The SL offspring showed higher plasma TSH, 3,5,3'-triiodothronine (T(3)) and thyroxine (T(4)) at 21 days (+60, +91 and +68%, respectively, P < 0.05), while the opposite was observed at 180 days regarding thyroid hormones (T(3), -10%; and T(4), -30%, P < 0.05), with no difference in TSH levels. In hypothalamus, no change was observed in the leptin signalling pathway at 21 days. However, lower janus thyrosine kinase 2 (JAK2) and phosphorilated-signal transducer and activator of transcription-3 (p-STAT3) content were detected in adulthood. In pituitary, the SL group presented higher leptin receptors (Ob-R), JAK2 and p-STAT3 content at 21 days and lower JAK2 and STAT3 content at 180 days old. In contrast, in thyroid, the Ob-R expression was lower in young SL rats, while the adult SL group presented higher Ob-R and JAK2 content. We showed that postnatal EO induces short- and long-term effects upon the hypothalamic-pituitary-thyroid axis. These changes may help to explain future development of metabolic and endocrine dysfunctions, such as metabolic syndrome and hypothyroidism.
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PMID:Postnatal early overnutrition changes the leptin signalling pathway in the hypothalamic-pituitary-thyroid axis of young and adult rats. 1948 48

Metabolic syndrome (MS) has become one of the topical health issues in developed countries. This arises from its increasing prevalence in the population linked to poor lifestyles (stress, overeating, lack of physical activity, smoking) and from its proven significantly negative association with the development ofatherosclerosis and thus increased cardiovascular mortality and morbidity. Nevertheless, the approaches to effective MS prevention are known as are the ways of treating and preventing MS sequelae. Prerequisite, however, is an early diagnosis of MS that should become integral to common clinical practice of internal as well as general medicine practitioners.
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PMID:[Metabolic syndrome]. 1973 64

The aim of this study was to model in mice the association between metabolic syndrome and the administration of atypical antipsychotic (AAP). Two dosages (4 and 8 mg/kg per day) of olanzapine (OL) were infused in 36 female mice for 30 days by osmotic mini-pumps. This study was also designed to further extend the implications raised in other experiments by our model of AAP-induced metabolic dysregulation. Through the use of the osmotic mini-pumps, this model is aimed to circumvent the shorter (than in humans) half-life of AAPs in rodents and to chronically administer OL by a reliable and less disturbing method. Indirect calorimetry was used to evaluate metabolic rate (MR) and respiratory exchange ratio together with weight and caloric intake. Serum insulin, leptin, and glucose tolerance (oral glucose tolerance test) were assessed. Pancreatic beta cells insulin levels, periuterine and liver fat content were also analyzed. Olanzapine-infused mice exhibited a reduction of overall MR (kilojoule per hour) and resting MR and respiratory exchange ratio, with periuterine fat significantly enlarged. All metabolic alterations were detected at the highest dose, with major effects found on weight gain and hyperphagia. Impaired glucose metabolism, associated with hyperinsulinemia and hyperleptinemia were found. Insulin resistance was evidenced by the raise of HOMA-IR index. Increased insulin and lipid storage were detected at pancreatic and hepatic levels respectively. These findings illustrate the development of a cluster of risk factors (metabolic syndrome) and, for the first time, a decrease of energy expenditure (MR) due to chronic OL infusion.
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PMID:30 days of continuous olanzapine infusion determines energy imbalance, glucose intolerance, insulin resistance, and dyslipidemia in mice. 1991 Jul 24

Diabetic patients tend to show a reduced QOL because of macrovascular complications such as cerebral and myocardial infarction, as well as marked microvascular complications. It is important for the prevention and amelioration of these complications to diagnose diabetes mellitus (DM) early and effectively control glycemia, the blood pressure, lipids, and body weight. We examine fasting plasma glucose (FPG) and HbA1c for a diagnosis of diabetes at any time, but examine 75gOGTT for impaired glucose tolerance or DM. Examination to be necessary for a pathologic classification of DM is islet-associated antibody, namely, GAD antibody, IA-2 antibody and the measurement of IRI, blood/urinary C-peptide to evaluate insulin secretory ability. HOMA-R is an index of insulin resistance, and HOMA-beta is an index of insulin secretory ability which can be calculated from FPG and IRI, but we need to be aware that the insulin secretory ability of the patient may have decreased already. HbA1c is a standard index of glycemic control, but glycoalbumin measurement is suitable for disease states such as anemia and liver cirrhosis, and 1,5-anhydroglucitol is suitable for detecting changes in levels of urinary glucose. Examinations necessary for the evaluation of diabetic nephropathy are microalbumin and 24hr Ccr in the urine, but eGFR has been recently recommended instead of 24hr Ccr. We measure small dense LDL-C, RLP-C, and Lp (a) as well as conduct conventional lipid analyses for dislipidemia combined with DM for qualitative as well as quantitative data. Metabolic syndrome is caused by the life habits of overeating and lack of exercise, leading to atherosclerotic disease, because insulin resistance advances from visceral fat accumulation. TNF-alpha and leptin levels as insulin resistance advances and adiponectin levels as insulin resistance improves are measured as adipocytokines secreted by visceral fat tissue.
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PMID:[Clinical laboratory examination of diabetic patients in conjunction with metabolic syndrome]. 2003 Jan 75

Altered nutritional experiences such as undernutrition, overnutrition, and modified milk formula in the immediate postnatal life via the phenomenon of metabolic programming have been identified as one of the components in the etiology of metabolic syndrome. We have developed a rat model in which an altered dietary experience in the form of a high-carbohydrate (HC) milk formula in the immediate postnatal life of rat pups results in chronic hyperinsulinemia and adult-onset obesity in these rats. The HC dietary modification causes functional alterations in pancreatic islets and the hypothalamus during the period of the dietary modification. These early adaptations in islets (supporting hyperinsulinemia) and the hypothalamus (supporting hyperphagia and increased body weight gain) persist in the postweaning period despite withdrawal of the HC milk formula at the time of weaning. In female rat pups receiving the HC milk formula, metabolic programming effects translate into an adverse (hyperinsulinemic, hyperleptinemic, and obese) intrauterine environment during pregnancy, causing spontaneous transfer of the maternal phenotype to the progeny (generational effect). Our results suggest that alterations in feeding practices for babies (early introduction of cereals, fruits, etc.) and babies born to obese/hyperinsulinemic mothers may be contributing factors for the obesity epidemic prevalent in developed and developing countries.
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PMID:Metabolic programming due to alterations in nutrition in the immediate postnatal period. 2010 49

Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual's risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.
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PMID:Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. 2148 25

Numerous clinical and experimental studies have linked stress to changes in risk factors associated with the development of physiological syndromes, including metabolic disorders. How different mediators of the stress response, such as corticosterone (CORT), influence these changes in risk remains unclear. Although CORT has beneficial short-term effects, long-term CORT exposure can result in damage to the physiological systems it protects acutely. Disruption of this important physiologic signal is observed in numerous disparate disorders, ranging from depression to Cushing's syndrome. Thus, understanding the effects of chronic high CORT on metabolism and physiology is of key importance. We explored the effects of 4-wk exposure to CORT dissolved in the drinking water on the physiology and behavior of male mice. We used this approach as a noninvasive way of altering plasma CORT levels while retaining some integrity in the diurnal rhythm present in normal animals. This approach has advantages over methods involving constant CORT pellets, CORT injections, or adrenalectomy. We found that high doses of CORT (100 microg/ml) result in rapid and dramatic increases in weight gain, increased adiposity, elevated plasma leptin, insulin and triglyceride levels, hyperphagia, and decreased home-cage locomotion. A lower dose of CORT (25 microg/ml) resulted in an intermediate phenotype in some of these measures but had no effect on others. We propose that the physiological changes observed in the high-CORT animals approximate changes observed in individuals suffering from the metabolic syndrome, and that they potentially serve as a model for hypercortisolemia and stress-related obesity.
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PMID:Endocrine and physiological changes in response to chronic corticosterone: a potential model of the metabolic syndrome in mouse. 2021 72

Postnatal early overnutrition (EO) is a risk factor for future obesity and metabolic disorders. Rats raised in small litters (SLs) develop overweight, hyperphagia, hyperleptinemia, hyperinsulinemia and hypertension when adults. As obesity is related to hyperleptinemia, leptin resistance and metabolic syndrome, we aimed to investigate body composition, plasma hormone levels, glucose tolerance and the leptin signaling pathway in hypothalamus from early overfed animals at weaning and adulthood. To induce postnatal EO, we reduced litter size to three pups/litter (SL), and the groups with normal litter size (10 pups/litter) were used as control. Rats had free access to standard diet and water postweaning. Body weight and food intake were monitored daily, and offspring were killed at 21 (weaning) and 180 days old (adulthood). Postnatal EO group had higher body weight and total and visceral fat mass at both periods. Lean mass and serum high-density lipoprotein cholesterol (HDL-C) were higher at 21 days and lower at 180 days. Small litter rats presented higher levels of globulins at both periods, while albumin levels were higher at weaning and lower at adulthood. There was higher leptin, insulin and glucose serum concentrations at 21 days old, while no glucose intolerance was observed in adulthood. Leptin signaling pathway was unaffected at weaning. However, postnatal EO induced lower JAK2 and p-STAT3, and higher SOCS3 expression in adult animals, indicating central leptin resistance in adulthood. In conclusion, postnatal EO induces obesity, higher total and visceral fat mass, lower HDL-C and central leptin resistance in adult life.
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PMID:Postnatal early overfeeding induces hypothalamic higher SOCS3 expression and lower STAT3 activity in adult rats. 2030 31


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