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At least 19 recordsLinked to original sources
PubMed1976

Triglyceride storage disease. A report of two affected children associated with neurological abnormalities.

Two children are described with congenital abnormalities (microcephaly, nystagmus, deafness, hepatomegaly) and the anomalous feature of triglyceride deposits in peripheral adipose tissue associated with severe malnutrition. Peripheral adipose tissue of one of these children displayed: (a) reduced sensitivity of adenyl cyclase to stimulation by noradrenaline (b) no response in tissue levels of cyclic AMP when stimulated by isoprenaline and (c) impaired release of glycerol following stimulation with isoprenaline. The other child, with similar clinical features, showed abnormal deposits of glycogen in the liver. It is postulated that a primary metabolic defect occurs in peripheral adipose tissue (and possibly at other sites such as the liver) that interferes with triglyceride (and glycogen) mobilization during prolonged malnutrition.

Abnormalities, Multiple↗
PubMed2026

Causal Relationships Between Modifiable Risk Factors and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder, yet the causal roles of modifiable risk factors remain unclear. This study aims to investigate the causal relationships between 28 modifiable risk factors (including obesity traits, mental health disorders, sleep traits, metabolic comorbidities, and serum parameters) and GERD using two-sample Mendelian randomization (MR). Gastroesophageal reflux disease (GERD). Our findings aim to inform targeted prevention and treatment strategies for GERD. METHODS: This study obtained data from extensive genome-wide association studies (GWAS). Pooled data associated with gastroesophageal reflux associations were obtained from the 23andMe Research team's research, which included a total of 129,080 cases of gastroesophageal reflux and 473,524 controls of European ancestry. We conducted a univariable Mendelian randomization (MR) analysis to ascertain whether genetic evidence of exposure demonstrated a statistically significant association with the risk of GERD. Subsequently, a multivariable MR analysis was carried out to estimate the independent effects of the exposures on GERD. RESULTS: Univariable MR analysis utilizing extensive GWAS data suggested that genetic factors such as BMI, Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), Attention Deficit and Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Schizophrenia, Negative emotions (including nervousness, anxiety, tension, or depression), Insomnia, Sleep apnea syndrome, Sleep duration, and Snoring, as well as Total cholesterol levels and Apolipoprotein B levels, are associated with the development of GERD. Multivariate Mendelian randomization of BMI and Negative emotion as correction factors showed that Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), ADHD, Insomnia, Sleep apnea syndrome, and Snoring were associated with an increased risk of GERD (p< 0.05). Conversely, longer sleep duration was associated with a reduced risk of GERD (p< 0.05). DISCUSSION: This MR study reveals novel causal mechanisms in GERD pathogenesis: (1) Peripheral adiposity (arm/leg fat mass) exerts independent effects beyond central obesity, indicating site-specific fat distribution significance; (2) ADHD emerges as a distinct psychiatric risk factor independent of mental disorders; (3) Sleep apnea operates through BMI-independent pathways. Collectively, these findings redefine GERD pathophysiology, highlighting fat depot specificity and brain-gut interactions as critical mechanistic drivers. CONCLUSION: Overall, our findings suggest that multiple risk factors are associated with the risk of GERD. These results provide a theoretical basis for controlling body weight and plasticity, improving sleep habits, and preventing and timely seeking medical attention to reduce the occurrence of psychiatric disorders, which will be important strategies to prevent and alleviate GERD.

Humans↗
PubMed1979

Simulated hyperglycemic hyperosmolar syndrome. Impaired insulin and epinephrine effects upon lipolysis in the isolated rat fat cell.

These investigations were designed to evaluate the effect of excess glucose and sodium chloride on lipolysis in the isolated adipocyte under normal and modelled pathological conditions simulating the hyperglycemic hyperosmolar syndrome. Isolated rat fat cells were incubated in the presence of various combinations of sodium chloride, glucose, epinephrine, and insulin. Lipolysis was measured as glycerol and free fatty acid release, and total medium osmolarity as milliosmoles per liter by freezing point depression. Basal lipolysis was unaffected by changes in osmolarity with sodium chloride, but glucose and glucose plus sodium chloride increased basal glycerol release. Increasing osmolarity with sodium chloride diminished the lipolytic response to epinephrine. Increasing osmolarity with glucose augmented the lipolytic response to epinephrine up to a total medium osmolarity of 550 mosmol. Higher osmolarities produced with glucose suppressed the epinephrine-induced lipolytic response.When the hyperglycemic hyperosmolar syndrome was simulated with 100 mM glucose and 50 mM sodium chloride (total osmolarity = 460 mosmol) the epinephrine-stimulated lipolysis dose-response curve in the isolated fat cell was shifted to the right. Furthermore, in the presence of 100 mM glucose + 50 mM sodium chloride, physiological concentrations of insulin were less effective in opposing epinephrine-stimulated lipolysis. In the presence of 50 mM glucose and 25 mM sodium chloride (total osmolarity = 370 mosmol) epinephrine-stimulated lipolysis measured as free fatty acid release was decreased by 50%. Under conditions simulating the hyperglycemic hyperosmolar syndrome in the isolated rat adipocyte, altered lipolysis reflects impaired effectiveness of both insulin and epinephrine as antilipolytic and lipolytic hormones, respectively. Furthermore, the attenuated response to both hormones appears to be primarily a function of extracellular solute composition. The lack of ketosis is the result of diminished release of free fatty acids from peripheral adipose cells.

Adipose Tissue↗
PubMed1977

[Endometrial cancer and extraglandular oestrogen biosynthesis (author's transl)].

An increasing incidence of endometrial cancer caused by a higher life expectancy and a number of other facters (i.e. obesity, diabetes, hypertension, lower pregnancy rate) as well as the unfavorable location for early detection when compared with cervical cancer has initiated this review in order to single out women with increased risk. Clinical characteristics of patients with endometrial cancer represented by age, menstrual disorders, reduced fertility, obesity, diabetes, hypertension, hirsutism, hyperplasia of the ovarian stroma or hilus cells in connection with an increased oestrogen effect in the vaginal smear and proliferative changes of the endometrium can be explained by extraglandular respectively peripheral aromatization of androgens to oestrogens, particular by the conversion of androstenedione to oestrone. This is supported by an increased plasma oestrone/oestradiol-ratio and increased conversion rate with age and overweight. In vivo- and in vitro-investigations have demonstrated the participation of adipose tissue in peripheral oestrogene production. The compiled data point towards the importance of the extraglandular oestrone production for the etiology of endometrial cancer by effecting the endometrium over a long period of time. The counter action of the normally cyclic changes of oestradiol and progesterone is lacking. Therefore, a dysoestrogenic effect of oestrone upon the endometrium can be fully effective, depending on the hormone receptor content of the respective endometrium. Based upon these data including recent publications, pre- and postmenopausal oestrogen therapy has to be critically reevaluated.

Adipose Tissue↗
PubMed1978

Lipoatrophic diabetes. Report of a case.

The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily.

Adult↗
PubMed1977

Free fatty acid turnover and the availability of substrates as a limiting factor in prolonged exercise.

A continual hydrolysis and release of FFA from the triglycerides stores of adipose tissue occurs during prolonged moderately severe exercise. The uptake and oxidation of plasma FFA by the working skeletal muscles represents a major source of energy during such exercise. During light and moderately intense prolonged exercise, lipolysis and the release of FFA from the adipose tissue exceeds uptake by peripheral tissue and the net result is an increase in plasma FFA levels. FFA uptake appears to be related to plasma concentrations and uses no membrane transport system. As work intensity increases the release of FFA from adipose tissue declines and the relative contribution of the plasma FFA to the work metabolism declines until at high work rates there is an almost complete reliance on the intramuscular glycogen reserves. At work loads above about 65% of the individual's aerobic capacity the limiting factor for prolonged exercise appears to be the glycogen stores of the working muscle. When these stores are depleted the work either must stop or its intensity be reduced. Trained individuals have a greater capacity to oxidize fats at high work loads than do untrained subjects. This, however, is not matched by an increased capacity for lipolysis. Why intramuscular glycogen stores are required for prolonged relatively severe exercise when the amount of FFA and glucose that perfuses the skeletal muscles under such conditions is theoretically capable of supporting the exercise metabolism is unknown.

Adipose Tissue↗
PubMed1979

Fat necrosis.

Fat necrosis has been found to be associated with many forms of pancreatitis, carcinoma of the pancreas and pancreatic trauma. The causative agents seem to be pancreatic lipase and colipase, which presumably escape from the pancreas during the development of the disease. The precise mechanism by which these factors attack the adipose tissue, leading to the formation of foci of fat necrosis, is not known. The pathologic finding of fat necrosis is not restricted to the peritoneal-retroperitoneal region, where a direct contact with these factors is the most likely cause. In other patients, fat necrosis involves peripheral tissues, notably in subcutaneous adipose tissue throughout the body, in joints of the hand and foot and in bone marrow. This is associated with additional complications dependent upon the sites involved and is manifested as skin lesions, polyarthritis and osteolytic defects in patients who sometime suffer from a primary pancreatic disease.

Acute Disease↗
PubMed1978

Thyrotropin receptors in adipose tissue, retro-orbital tissue and lymphocytes.

Thyrotropin (TSH) receptors on retro-orbital muscle and fat have been implicated in the pathogenesis of Graves' exophthalmos and it has been suggested that TSH has a direct effect on human fat metabolism. We have therefore investigated the interaction of biologically active 125I-labelled TSH with membranes prepared from human adipose, retro-orbital and thyroid tissue. Since lymphocytes contain receptors for several polypeptide hormones, TSH binding to lymphocyte membranes was also studied. We were unable to demonstrate TSH receptors in adult human adipose tissue, retro-orbital muscle and fat, or peripheral blood lymphocytes. In contrast, adult and neonatal guinea pig adipose tissue membranes showed similar TSH binding characteristics to guinea pig thyroid membranes.

Adipose Tissue↗
PubMed1978

Amino acid derangements in patients with sepsis: treatment with branched chain amino acid rich infusions.

Sepsis is a major catabolic insult resulting in modifications in carbohydrate and fat energy metabolism, and leading to increased muscle breakdown and nitrogen loss. Insulin resistance, which develops in sepsis, decreases glucose utilization, but plasma insulin levels are sufficiently elevated to prevent lipolysis, resulting in a further energy deficit. The availability of fuels in sepsis is therefore limited, and the body resorts to muscle breakdown, gluconeogenesis, and amino acid oxidation for energy supply. Previous work has not defined, however, the exact alterations in amino acid metabolism. Therefore, the following studies were undertaken. Blood samples were drawn from fifteen patients in whom the diagnosis of sepsis was clinically established; the samples were analyzed for amino acid, beta-hydroxyphenylethanolamines, glucose, insulin and glucagon concentrations. The plasma amino acid pattern observed was characterized by an increase in total amino acid content, due mainly to high levels of the aromatic amino acids (phenylalanine and tyrosine) and the sulfur-containing amino acids (taurine, cystine and methionine). Alanine, aspartic acid, glutamic acid and proline were also elevated, but to a lesser degree. The branched chain amino acids (valine, leucine and isoleucine) were within normal limits, as were glycine, serine, threonine, lysine, histidine and tryptophan. Those patients who did not survive sepsis had higher levels of aromatic and sulfur-containing amino acids as compared to those patients surviving sepsis. On the other hand, those patients surviving sepsis had higher levels of alanine and the branched chain amino acids. In a second group of five patients with overwhelming sepsis accompanied by a state of metabolic encephalopathy, a parenteral nutrition solution consisting of 23% dextrose, and an amino acid formulation enriched with branched chain amino acids was administered. In these five patients, normalization of the plasma amino acid pattern and reversal of encephalopathy was observed. The following sequence of events may be postulated: The septic patient develops insulin resistance in the peripheral tissues, primarily muscle, while the adipose tissue is much less affected. The insulin resistance and the inability to utilize fat leads to increased muscle proteolysis. Muscle breakdown results in release into the blood of enormous amounts of various amino acids; the muscle itself is able to oxidize the branched chain amino acids, supplying the muscles' own energy requirements and alanine for gluconeogenesis. The extensive muscle proteolysis coupled with relative hepatic insufficiency occurring early in sepsis results in the appearance in the plasma of high levels of most of the amino acids present in muscle, particularly the aromatic and the sulfur-containing amino acids. The outcome of patients with sepsis might be positively affected by combined therapy with glucose, insulin and branched chain amino acids.

Amino Acids↗
PubMed1979

A clinicopathological study on soft tissue tumors of the head and neck.

The present study consists of 651 cases of soft tissue tumors originating in the head and neck area. Among these tumors 628 were benign (96%), while there were only 23 malignant cases (4%). In the benign group hemangiomas showed the highest incidence (47%) followed by tumors of adipose tissue (19%) and those of peripheral nerves (12%). Rare tumors consisted of nodular fascitis, hibernoma, lipoblastomatosis, glomus tumor, granular cell tumor, and chondroma. The majority of cases in the malignant group were either those of muscle origin or blood vessel origin. Excepting for two cases of rhabdomyosarcoma of the embryonal type and two cases of angiosarcoma, all showed recurrence and/or metastasis and terminated in death. Three cases of liposarcoma of either well-differentiated or myxoid type had a good prognosis with all three living for 3 or more years without any recurrence. Other malignant tumors consisted of malignant schwannoma, fibrosarcoma, malignant fibrous histiocytoma, alveolar soft part sarcoma, and chordoma. The age, sex, anatomical location, and differential diagnosis have also been described.

Adolescent↗
PubMedDate not supplied

[Disorder of the activity of the cardiovascular system in obesity in children and adolescents].

The author describes the results of study carried out in 171 children aged from 6 to 14 years suffering from adiposity of the constitutional-exogenous and neuro-endocrine form. A complicated character of hemodynamic dicturbances in adiposity (intensified cardiac activity, hyperdynamia replaced by the hypodynamia of the myocardium syndrome in marked degrees of adiposity, incoordination between the central and the peripheral circulation links is noted. All this points to the early involvement of the heart and the vessels in the pathological process.

17-Ketosteroids↗
PubMed1977

Effect of physical exercise on erythrocyte lipids, biliary cholesterol and bile lithogenicity in rats.

Male Wistar rats were exercised (E) by daily 1 h swimming for 24 days. Sedentry controls (S) were caged individually. Bile analysis at the end of the experiment (24 h after the last exercise) showed a decrease in bile cholesterol (CH) (P less than 0.02) and phospholipids (PL) (P less than 0.01) in the exercising animals, but no significant change in the bile acids (BA). These changes in the exercising rats resulted in a decreased CH saturation of bile: in an improvement in the (BA + PL)/CH ratio (P=0.05) and a trend to a decrease in the per cent saturation of bile CH. Exercise did not affect the bile flow or bile acid flux rate. Exercise decreased erythrocyte phospholipids (P less than 0.01). The effect of exercise on bile was associated with a trend to lower CH in the erythrocytes and in the adipose tissue and thus most likely does not represent a shift of cholesterol from the liver to the peripheral tissues. Physical exercise may be a preventive factor in cholesterol gallstone formation.

Adipose Tissue↗
PubMed1977

Hypoglycemia induced by alpha-adrenergic stimulation during alkalosis.

Hypoglycemia developed during respiratory alkalosis in fasted rats. This hypoglycemia was markedly potentiated by the simultaneous injection of inhibitors of hepatic gluconeogenesis or a beta-adrenergic blocking agent; was not influenced by anti-insulin serum; was attenuated by hexamethonium; and was abolished by an alpha-adrenergic blocking agent. The rate of removal of injected glucose by peripheral tissues increased during alkalosis in insulin-deficient rats. The uptake of [14C]-glucose by the adipose tissue in vivo, which is stimulated by a very minute amount of insulin, was also stimulated during alkalosis whether or not the circulating insulin was neutralized with anti-insulin serum. It was concluded that, in alkalotic rats, blood glucose is rapidly utilized by peripheral tissues dependent on alpha-adrenergic stimulation, but without mediation of insulin and that this leads to development of hypoglycemia.

Alkalosis, Respiratory↗
PubMed1975

Metabolism of 14C-dehydroepiandrosterone in female adipose tissue and venous blood.

The metabolism of dehydroepiandrosterone in female adipose tissue and venous blood in 11 patients was studied by a double isotope method which is described in detail. The main metabolite isolated, identified and quantitated was androstenediol. The conversion rate of dehydroepiandrosterone to androstenediol for adipose tissue ranged between 3.32-14.28% (X = 7.47 +/- 3.34 SD) and for venous blood between 2.88-9.60% (X = 5.84 +/- 1.80 SD). The values found for androstenedione and testostrone did not differ from the control experiments. Oestrone and oestradiol could not be detected. The contribution of the peripheral steroid metabolism to the pool of androgenic steroids is discussed.

Adipose Tissue↗
PubMedDate not supplied

Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridaemia: effects of 2,2-dimethyl, 5(2, 5-xylyoxy) valeric acid therapy.

The effects of C1-719 on plasma lipid and lipoprotein concentrations have been examined in four patients with endogenous hypertriglyceridaemia maintained on an isocaloric diet for a period of 6 months. During therapy (400 mg/day) the mean plasma triglyceride and cholesterol concentrations were reduced by 35% and 15% respectively, while the administration of 800 mg/day reduced these by 49% and 31%. This hypolipidaemic effect was due to a reduction in the circulating level of very low density lipoproteins (VLDL) without a change in their composition. Before treatment the plasma VLDL triglyceride turnover, and FFA flux, were higher than that of normal subjects maintained on a similar diet. The plasma VLDL B-apoprotein turnover was similarly higher than in the controls. Administration of C1-719 decreased the plasma VLDL triglyceride turnover, FFA flux and VLDL B-approtein turnover. The drug reduced the insulin response following a glucose load with some decrease in glucose levels. The results suggest that the increase in plasma triglyceride concentration in patients with endogenous hypertriglyceridaemia is due to increased production of plasma VLDL triglyceride and its apoptein associated with an enhanced supply of FFA for hepatic triglyceride synthesis. C1-719 exerts a hypolipidaemic effect through a reduction of VLDL production, consequent upon inhibition of lipolysis as well as decreased synthesis of the apoprotein carrier. These effects could in part be explained by an improvement in peripheral tissue responsiveness to insulin and decreased exposure of the liver to high levels of insulin. However, a direct effect of the drug on adipose tissue and liver metabolism has to be considered.

Adult↗
PubMed1977

An involvement of alpha-adrenergic stimulation in exercise-induced hypoglycemia.

Hypoglycemia developed in fasted rats during forced swimming. This hypoglycemia was mostly abolished by phentolamine, an alpha-adrenolytic agent, or by hexamethonium; was potentiated by propranolol, a beta-adrenolytic agent, of by 5-methoxyindole-2-carboxylic acid, a gluconeogenic inhibitor; and was not affected by anti-insulin serum. The turnover rate of blood glucose estimated from the decay curve of blood [14C]glucose increased significantly during exercise. There was a slight but significantly increase during exercise in the transfer of 3-O-methyl-[14C]glucose into muscle and adipose tissues, when it was corrected for by [3H]mannitol transfer to the same tissues. It is concluded that the alpha-receptor-mediated action of endogenous catecholamine stimulates peripheral glucose utilization leading to hypoglycemia during exercise. The action of alpha- and beta-adrenergic mechanisms, directly on peripheral tissues or via insulin secretion, in fine regulation of blood glucose level is discussed.

Animals↗