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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid mobilizing substances (LMS) are present in the hypothalamus and pituitary of mammals and probably are involved in the central neural control of obesity. Most of these have direct lipolytic effects, like lipid mobilizing factor (LMF) and LH-RH from the hypothalamus as well as lipotropin (LPH), melanocyte-stimulating hormone (MSH), corticotropin (ACTH), and growth hormone (GH) from the pituitary gland. Some of the substances, like GH-release inhibiting hormone (GH-RIH), affect lipolysis by secondary actions on pancreatic hormones such as insulin and glucagon. Other hypothalamic hormones, like GH-releasing hormone (GH-RH) may influence lipolysis secondarily through the pituitary hormones (e.g. GH) whose release they control. Regardless of how lipid mobilization is affected, investigations into the problem of obesity should take these LMS into consideration.
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PMID:Lipid mobilizing hormones of the hypothalamus and pituitary. 17 3

1. Male rats were injected daily for 5 days with 0.15m-NaCl, corticotropin, cortisol or l-thyroxine and the rates of glycerolipid synthesis were measured in the livers after intraportal injection of [(14)C]palmitate and [(3)H]glycerol. 2. Injection of all three hormones decreased the rates of body-weight gain. 3. Cortisol treatment increased the weight of the liver relative to body weight. 4. Thyroxine treatment increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol and decreased the relative accumulation of (3)H and (14)C in diacylglycerol. It did not significantly alter the accumulation of these isotopes in phosphatidate nor the activity of the soluble phosphatidate phosphohydrolase in the total liver. However, this activity increased by 1.5-fold when expressed relative to the soluble protein of the liver. The increased triacylglycerol synthesis appears to be related to a general increase in the turnover of fatty acids in the liver. 5. Treatment with cortisol and corticotropin increased the relative rate of triacylglycerol synthesis from [(3)H]glycerol, decreased the accumulation of (3)H in phosphatidate and increased the flux of both isotopes from phosphatidate to diacylglycerol. This appeared to be caused by the increased activity of the soluble phosphatidate phosphohydrolase that was observed in the livers of the cortisol-treated rats. 6. It is proposed that cortisol could be directly or indirectly involved in increasing the activity of hepatic phosphatidate phosphohydrolase in starvation, diabetes, laparotomy, subtotal hepatectomy, liver damage, ethanol feeding and in obesity. This enzyme adaptation could contribute to the potential of the liver to increase its synthesis and accumulation of triacylglycerols or to secrete very-low-density lipoproteins.
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PMID:The effects of cortisol, corticotropin and thyroxine on the synthesis of glycerolipids and on the phosphatidate phosphohydrolase activity in rat liver. 21 53

The common obesity of middle age presents a set of features that strongly resembles the cardinal symptoms of Cushing's syndrome: obesity of the face (moon face), upper back (buffalo hump) and trunk (pot belly) accompanied by signs of protein-wasting. In non-obese individuals who remain at a constant weight throughout life, the proportion of adipose tissue increases with age at the expense of lean tissue loss. Thus, a mild version of Cushing's syndrome may be part of the normal aging process. A more intense version of this process may occur in overweight adults. Excess and chronic activity of two pituitary hormones may contribute to this adiposity. Both hormones are produced in the same pituitary cell by cleavage from a common large precursor known as pro-opiocortin. One hormone is adrenocorticotrophin (ACTH), which stimulates the release of the glucocorticoid hormones. These hormones promote the conversion of bodily proteins to glucose (gluconeogenesis). The other pituitary hormone is beta-endorphin, a stimulant of appetite that causes the release of insulin. This pancreatic hormone promotes the conversion of glucose and fatty acids to triglycerides (lipogenesis). Three different etiologies are suggested for the excessive and chronic action of these two pituitary hormones: tumors that increase the number of cells that synthesize pro-opiocortin; mutant strains that produce excessive amounts of ACTH and beta-endorphin such as the genetically obese mouse (ob/ob) and rat (fa/fa); and an age-determined shift in the type of cleavage enzymes present in the pro-opiocortin cell that favors ACTH and beta-endorphin production.
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PMID:The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity. 22 74

Plasma cortisol response induced by 2.5 microgram/kg beta 1-24 corticotropin (1 hour infusion) in obese females was not related to fat mass. The response was increasingly pronounced as fat predominated in the upper body segment, i.e. android obesity. This phenomenon may be interpreted as indicating an increased adrenal capacity to secrete cortisol in such obese patients. Low level but longstanding excess cortisol secretion is probably the cause of the android features of obesity.
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PMID:[Plasma cortisol response to intravenous beta 1-24 corticotropin as related to the fat mass and its topographic localisation (author's transl)]. 22 18

Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences.
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PMID:Cushing's syndrome and acute lymphoblastic leukemia. 27 79

Compared to littermate controls (C57BL/6J ob/?), body weights of genetically obese (ob/ob) mice are significantly higher at 1-6 months of age; the greatest percentage weight gain of the ob/ob group occurs during the first 3 months of life. Levels of pituitary immunoreactive beta-endorphin and immunoreactive alpha-melanocyte-stimulating hormone are also significantly elevated in ob/ob animals compared to controls. However, these pharmacological differences only emerge at 4-6 months of age--3 months after the appearance of obesity. High levels of immunoreactive endorphin in the pituitary are, therefore, more likely to be a consequence than a cause of obesity. Furthermore, numerous other neurologic abnormalities, which may or may not play a role in the obesity syndrome, are evident in ob/ob mice. Compared to controls, ob/ob total brain, hypothalamus, and pituitary weights are 11%, 16%, and 23% less, respectively. Levels of immunoreactive Leu5-enkephalin in pars nervous are also 200% higher in ob/ob mice; this increase is apparent at 1-6 months of age and is highly correlated with changes in body weight.
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PMID:Opioid peptides and alpha-melanocyte-stimulating hormone in genetically obese (ob/ob) mice during development. 28 46

Small doses of the opiate antagonist naloxone selectively abolished overeating in genetically obese mice (ob/ob) and rats (fa/fa). Elevated concentrations of the naturally occurring opiate beta-endorphin were found in the pituitaries of both obese species and in the blood plasma of the obese rats. Brain levels of beta-endorphin and Leu-enkephalin were unchanged. These data suggest that excess pituitary beta-endorphin may play a role in the development of the overeating and obesity syndrome.
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PMID:beta-Endorphin is associated with overeating in genetically obese mice (ob/ob) and rats (fa/fa). 71 55

Eighteen patients treated with prednisone on alternate days for varying degrees of alopecia areata (AA) were examined a mean of 15 months after discontinuation of the drug. Despite an initial response to the therapy, long-term benefit was not thought to be substantial. Numerous side effects related either to systemic corticosteroids or to AA were apparent during the course of therapy, as well as at the time of the evaluation reported herein. Acne, obesity, lenticular opacities, mild hypertension, and impaired adrenocorticotropic hormone (ACTH) reserve were among the findings noted. Long-term treatment was not accompanied by an obvious beneficial change in the natural course of AA. Because of the potentially serious side effects and the lack of substantial improvement in the eventual course, alternate-day prednisone therapy is not recommended for long-term use in AA.
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PMID:Prednisone therapy for alopecia areata. A follow-up report. 79 Nov 52

We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma.
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PMID:Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma. 128 18

To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 microgram/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d-FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 microgram/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 +/- 11.2 ng/mL v 104.1 +/- 9.5 ng/mL). This response was lower (P less than .005) than in the controls, in whom the basal cortisol value of 120.6 +/- 11.8 ng/mL reached a peak value of 221.2 +/- 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P less than .0001) plasma cortisol (peak value 170.6 +/- 18.0 ng/mL v 111.5 +/- 10.8 ng/mL) and the response was enhanced (P less than .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 +/- 1.7 pg/mL v 9.6 +/- 1.1 pg/mL), but the hormonal response was lower (P less than .005) than in controls (peak value 38.1 +/- 5.5 pg/mL v 13.8 +/- 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P less than .05) in plasma ACTH at 30 minutes (20.4 +/- 3.7 pg/mL v 10.9 +/- 0.9 pg/mL) and 45 minutes (18.0 +/- 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects. 131 2


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