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PubMed1990

Isolation and structure of a novel charged member of the red-pigment-concentrating hormone-adipokinetic hormone family of peptides isolated from the corpora cardiaca of the blowfly Phormia terraenovae (Diptera).

A hypertrehalosaemic neuropeptide from the corpora cardiaca of the blowfly Phormia terraenovae has been isolated by reversed-phase h.p.l.c., and its primary structure was determined by pulsed-liquid phase sequencing employing Edman chemistry after enzymically deblocking the N-terminal pyroglutamate residue. The C-terminus was also blocked, as indicated by the lack of digestion when the peptide was incubated with carboxypeptidase A. The octapeptide has the sequence pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-NH2 and is clearly defined as a novel member of the RPCH/AKH (red-pigment-concentrating hormone/adipokinetic hormone) family of peptides. It is the first charged member of this family to be found. The synthetic peptide causes an increase in the haemolymph carbohydrate concentration in a dose-dependent fashion in blowflies and therefore is named 'Phormia terraenovae hypertrehalosaemic hormone' (Pht-HrTH). In addition, receptors in the fat-body of the American cockroach (Periplaneta americana) recognize the peptide, resulting in carbohydrate elevation in the blood. However, fat-body receptors of the migratory locust (Locusta migratoria) do not recognize this charged molecule, and thus no lipid mobilization is observed in this species.

Amino Acid Sequence↗
PubMed2003

The glutamine 27 glutamic acid polymorphism of the beta2-adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain.

OBJECTIVE: Given the important role of the beta2-adrenoceptor (beta2-AR) in lipid mobilization and the lack of studies in Southern European countries, the aim of this study was to investigate the role of the glutamine 27 glutamic acid (Gln27Glu) beta2-AR polymorphism in the susceptibility to obesity and its metabolic complications in a population-based nationwide multicentre study in Spain, especially focusing on the hypothetical influence of gender. DESIGN: Cross-sectional population-based study. PATIENTS: We studied 666 nonrelated adults (47.9% men and 52.1% women), aged 35-64 years, chosen randomly from a nationwide population-based survey of obesity, and related conditions including insulin resistance and cardiovascular risk factors. MEASUREMENTS: Body mass index (BMI), waist-to-hip ratio (WHR), sagittal abdominal diameter (SAD), systolic and diastolic blood pressure, fasting and 2-h post-glucose load glycaemic levels, total cholesterol, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, triglycerides, insulin, proinsulin and leptin plasma levels were measured. Beta2-AR Gln27Glu genotypes were determined by restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR). RESULTS: Glu27 homozygous obese men had significantly higher BMI and SAD mean values than both heterozygous and Gln27 homozygous obese men. Two-hour post-load plasma glucose concentration was higher in Glu27 homozygous than in Gln27 homozygous in the whole population and only in men when stratified by gender. No differences according to the genotype were found for the rest of the parameters studied, including homeostasis model assessment (HOMA), insulin, proinsulin and leptin levels, but for total and LDL-cholesterol these increased in men. We did not find differences in the anthropometrical and biochemical parameters according to the genotype in women. Multivariate logistic regression analysis showed that Glu27 homozygosity after adjustment for SAD was associated with type 2 diabetes mellitus. CONCLUSIONS: Our results suggest that the glutamic acid 27 allele of the beta2-adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the development of type 2 diabetes mellitus.

Adult↗
PubMed2003

Energy balance and pollution by organochlorines and polychlorinated biphenyls.

Organochlorines are fat-soluble chemical compounds resistant to degradation, so they are stored in the adipose tissue of practically every organism on the planet, including humans. Accumulation of these compounds in the body seems to be related to fat mass, obese individuals having a higher plasma organochlorine concentration than lean subjects. During body weight loss, lipid mobilization and a decrease in fat mass result in increased concentrations of organochlorines in plasma and adipose tissue. Organochlorines may have adverse health effects. For example, they have been associated with altered immune and thyroid functions and with some types of cancer. As these compounds may reach their target organs whilst in the circulation, their increase in plasma during weight loss might be associated with some physiological changes occurring during weight loss. Relationships have indeed been reported among weight loss-induced increase in plasma organochlorine concentration and decreased triiodothyronine (T3) concentration, resting metabolic rate, and skeletal muscle markers for fat oxidation. Although further studies are needed to assess the causality of these relationships, they raise concern about some potential undesirable effects of weight loss. Indeed, the effects of organochlorines on energy balance could complicate body weight loss and even favour weight regain. These notions lend support for weight-loss strategies favouring a moderate weight loss, which would reduce risks for cardiovascular diseases, diabetes and hypertension, without resulting in a substantial release of organochlorines.

Adipose Tissue↗
PubMed2002

Significance of beta2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects.

Catecholamines play a central role in the regulation of energy expenditure, in part stimulating lipid mobilization through lipolysis in fat cells. The beta(2)-adrenergic receptor (ADRB2) is a major lipolytic receptor in human fat cells, and a recent study has shown that common polymorphisms occurring in codons 16 and 27 of the ADRB2 gene are significantly associated with obesity and lipolytic ADRB2 function in adipose tissue. We investigated whether previously described human ADRB2 gene polymorphisms are associated with obesity and diabetes in Korean subjects. According to the World Health Organization (WHO) criteria for oral glucose tolerance testing, 57 subjects had normal glucose tolerance (NGT), 32 had impaired glucose tolerance (IGT), and 106 had diabetes mellitus. The nondiabetic group (including NGT and IGT) consisted of 46 obese (defined as those with body mass index [BMI] of >or= 27 kg/m(2)) and 43 nonobese subjects (BMI < 27 kg/m(2)). The subjects with diabetes consisted of 62 obese and 44 nonobese subjects. There was no significant difference between nonobese and obese subjects in the allele frequency of ADRB2 gene polymorphisms at codons 16 and 27. There were no significant differences in BMI, percentage body fat, waist-to-hip ratio (WHR), systolic blood pressure, diastolic blood pressure and concentrations of fasting plasma glucose, fasting serum insulin, serum low-density lipoprotein (LDL)-cholesterol, serum high-density lipoprotein (HDL)-cholesterol, serum triglyceride, and serum free fatty acids, according to ADRB2 gene polymorphisms at codons 16 and 27. The frequency of the Glu27 homozygote was 1.1%. These findings suggest that genetic variability in the ADRB2 gene may not be a major determinant for the development of obesity and diabetes in Koreans.

Adult↗
PubMed2002

Effect of macronutrient composition of the diet on the regulation of lipolysis in adipose tissue at rest and during exercise: microdialysis study.

The aim of the present study was to elucidate, using a microdialysis technique, whether modifications in the proportion of fat in the diet influence lipid mobilization from adipose tissue in situ. Nine healthy volunteers (age, 23.4 +/- 0.2 years; body mas index [BMI], 23.5 +/- 1.6 kg/m(2)) were fed, in random order, with a high-fat diet (HFD) (65% of energy content fat, 15% protein, 20% carbohydrate) or a high-carbohydrate diet (HCD) (70% carbohydrate, 15% protein, 15% fat) for 5 days, with a washout period of 10 days between the diets. Subjects were studied in the fasting state on the morning following days 4 and 5 of each diet. We measured the concentration of extracellular glycerol (EGC) in adipose tissue in response to (1) pharmacologic stimulation with isoprenaline (1 and 10 micromol/L) in situ, (2) stimulation with intravenous infusion of epinephrine (0.0375 microg/min/kg body weight), and (3) submaximal aerobic exercise (50% V*O2max, 60-minute duration). No effect of the diet composition was found in the increases of EGC in response to isoprenaline (area under the curve [AUC]: HFD, 1,534 +/- 370 micromol/90 min; HCD, 1,108 +/- 465 micromol/90 min; not significant [NS]) or epinephrine stimulations (AUC: HFD, 190 +/- 92 micromol/30 min; HCD, 251 +/- 298 micromol/30 min; NS). The exercise-induced increase in EGC was higher during the HFD (AUC: HFD, 1,641 +/- 181 micromol/60 min; HCD, 963 +/- 156 micromol/60 min; P <.05) and was associated with a higher exercise-induced response of norepinephrine (P <.05) and epinephrine (P =.056) and lower insulinemia during exercise. The results suggest that macronutrient composition of diet does not affect the beta-adrenergic responsiveness of adipose tissue to catecholamine action at rest. During exercise, the HFD promotes higher lipolysis in adipose tissue and this is associated with a higher catecholamine response and lower insulinemia.

Adipose Tissue↗
PubMed1979

Effects of histamine, of histidine and of anti-histaminic agents on the release of glucagon and insulin from the rat pancreas.

We have studied the effect of histamine (HA) and histidine (HIS) on the release of immunoreactive glucagon (IRG) and insulin (IRI) by isolated rat islets and pieces of pancreas. In isolated islets, HA and HIS stimulated IRG release at a glucose concentration of 3.0 mg/ml and IRI release at a glucose concentration of 0.5 mg/ml. In pieces of pancreas incubated in the presence of glucose (3.0 mg/ml), HA at a 2mM concentration stimulated IRG release and had no effect on the release of IRI; however, when the concentration of HA was doubled (4 mM), an inhibition of IRI release could also be demonstrated. HIS was ineffective. Perphenazine and dexchlorpheniramine, two anti-histaminic agents, inhibited IRG and stimulated IRI release. These results indicate that histamine, whether endogenous or exogenous, directly stimulated IRG and inhibits IRI release and suggest that some of the in vivo effects of histamine, such as hyperglycemia and lipid mobilization, may be mediated, at least in part, by these endocrinologic effects.

Animals↗
PubMed2002

Metabolic and hemodynamic responses to exercise in subcutaneous adipose tissue and skeletal muscle.

This study evaluated the effect of standardized bicycle exercise on metabolism and blood flow in abdominal ( aSAT) and femoral subcutaneous adipose tissue ( fSAT) and skeletal muscle in eleven women and nine men. Using microdialysis, the respective tissues were perfused with Ringer's solution (+ 50 mM ethanol) and dialysate [ethanol], [glycerol], [lactate] and [pyruvate] were measured in order to estimate blood flow (ethanol dilution technique), lipolysis and glycolysis, respectively. At rest, blood flow tended to be higher in the respective tissues of women when compared to men. During exercise, blood flow was increased significantly in fSAT and muscle, but not in aSAT. Dialysate [glycerol] was increased two- to three-fold in aSAT and fSAT, similarly in men and women. However, in muscle, dialysate [glycerol] was increased five-fold in women and four-fold in men without reaching a steady state in women. Corrected for blood flow, the increase in lipolysis was greater in muscle than in fSAT, and greater in fSAT than in aSAT, and in muscle the increase was greater for women compared with men. Dialysate [lactate] and [lactate]/[pyruvate] ratio were much more increased in muscle compared with aSAT and fSAT. It is concluded that lipids stored in muscle are rather used than lipids stored in adipose tissue for fueling the energy metabolism of muscle during exercise. During exercise, lipid mobilization is much greater in women than in men.

Abdomen↗
PubMedDate not supplied

Relationship between serum adiponectin concentration and intramyocellular lipid stores in humans.

The recently identified adipocytokine adiponectin has been shown to improve insulin action and decrease triglyceride content in skeletal muscle (by stimulating lipid oxidation) in mice. In the present study, we tested the hypothesis that high serum concentrations of adiponectin are associated with lower intramyocellular (IMCL) fat content by promoting lipid oxidation in humans. IMCL-content in predominantly non-oxidative tibialis anterior muscle and oxidative soleus was determined by proton magnetic resonance spectroscopy in a cross- sectional study involving 63 healthy volunteers. In a second set of experiments, changes in IMCL in both muscles were measured after a three days dietary lipid challenge (n = 18) and after intravenous lipid challenge (n = 12) with suppressed lipid oxidation under hyperinsulinemia. Adiponectin serum concentrations were found to be negatively correlated with IMCL in the oxidative soleus muscle (IMCL [sol]) (r = - 0.46, p < 0.001) independent of measures of obesity, but not with IMCL in the non-oxidative tibialis anterior muscle (IMCL [tib]) (p = 0.40). Adiponectin serum concentrations were negatively correlated with the observed increase in IMCL load after dietary lipid challenge in the tibialis (r = 0.53, p = 0.03) but not in the soleus muscle. During suppression of lipid oxidation by hyperinsulinemia, no effect of adiponectin on IMCL was observed in either soleus or tibialis muscle. Overall, the presented findings are consistent with the hypothesis that adiponectin promotes lipid oxidation in humans resulting in lower intracellular lipid content in human muscle. These results are consistent with animal data, where adiponectin could be shown to enhance lipid oxidation and reduce muscle triglycerides.

Adiponectin↗
PubMed2005

Lipolytic activity of cirsimarin extracted from Microtea debilis.

This study explores the ability of cirsimarin, a plant flavonoid, to trigger lipid mobilization. Cirsimarin was extracted from Microtea debilis Swartz (Phytolaccaceae) and purified by preparative HPLC. Its lipolytic activity was assessed on isolated adipocytes from rats and compared to that of caffeine, a well known lipolytic agent. The results show an EC (50) = 0.025 +/- 0.01 mM for cirsimarin (n = 4) and of 0.49 +/- 0.08 mM for caffeine (n = 4). Furthermore, we show that cirsimarin inhibits phosphodiesterase, the enzyme that modulates cyclic nucleotide signalling. In conclusion, our results demonstrate that cirsimarin exerts strong lipolytic properties being 20 times more potent than caffeine to stimulate lipolysis, at least in part through cyclic nucleotide preservation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Post receptor activation of lipolysis in starvation, diabetes mellitus and hyperthyroidism.

Activation of lipolysis by cyclic AMP in conditions with accelerated lipid mobilization was examined in subcutaneous adipose tissue incubated in vitro. In (a) 16 obese patients before and during therapeutic starvation, (b) 18 diabetics before and after antidiabetic treatment and (c) 11 hyperthyroid patients before and after anti-thyroid treatment, a positive correlation was found between stimulation of basal cyclic AMP accumulation and stimulation of basal glycerol release using either isopropyl noradrenaline or noradrenaline (r = 0.6-0.9). During antidiabetic treatment stimulation of lipolysis increased in relation to that of cyclic AMP accumulation (F = 10.1, p less than 0.01), whereas during antithyroid therapy there was a decrease (F = 95.2, p less than 0.01). Starvation did not alter the relationship between lipolysis and cyclic AMP in hypogastric adipose tissue whereas in femoral tissue stimulation of lipolysis decreased in relation to that of cyclic AMP accumulation (F = 9.6, p less than 0.01). It is concluded that the amount of cyclic AMP needed to promote lipolysis is increased during starvation and in diabetes mellitus but is decreased in hyperthyroidism. From the studies during starvation it appears that regional differences in the post-receptor activation of lipolysis exist in human adipose tissue.

Adult↗
PubMed1988

Restricted alpha- and beta-adrenoceptor affinity of sulfoconjugated catecholamines in human mononuclear leukocytes, platelets, and fat cells and reduction of the postreceptor mechanisms.

The physiologic significance of the racemic 3-O-sulfate esters of epinephrine (EPI-3-O-S) and norepinephrine (NE-3-O-S) as well as 4-O-sulfoconjugated dopamine (DA-4-O-S) was evaluated. For this purpose these conjugated catecholamines (CA) were synthesized and investigated with respect to their alpha 2- and beta 2-adrenoceptor affinities and their biological activity in three different human cell systems: in mononuclear leukocytes (MNL), platelets, and fat cells. The unequivocal identification and the minimal degree of contamination of the synthesized sulfoconjugates with free CA was proved by 1H-NMR and by high-performance liquid chromatography with amperometric detection (HPLCA) respectively. In isolated human MNL, beta-adrenoceptor affinities of these conjugated CA were determined in competition experiments with the lipophilic nonspecific radioligand (-) 125I-cyanopindolol (ICYP) and, in addition, with the hydrophilic ligand 3H-CGP12177. With both ligands the affinity constants (KD) of the sulfoconjugated CA under investigation were about 100- to 1000-fold higher when compared with the respective free amines. Moreover, these sulfoconjugated CA per se induced no intracellular production of cyclic adenosine monophosphate (cAMP) in MNL. In comparison with the free amines, metanephrine (MN) and normetanephrine (NMN) showed a highly reduced competitive potency on the MNL beta-adrenoceptors labelled with 3H-CGP or ICYP. The KD values for MN and NMN in competition studies with ICYP were 10- and 5-fold higher than in those with 3H-CGP respectively, indicating a restricted access of MN and NMN to intracellular receptors. The adenylate cyclase system was not stimulated at all by MN or by NMN. In human platelets EPI-3-O-S and NE-3-O-S neither competed with the specific alpha 2-adrenoceptor antagonist 3H-yohimbine nor elicited any aggregation response at all. MN and NMN exhibited an about 40-fold reduced affinity for alpha 2-adrenoceptors in platelets when compared with the respective free amines and elicited no aggregation response at all. However, in the presence of MN and NMN the EPI- and NE-induced platelet aggregation was dose-dependently attenuated. These findings reveal an alpha 2-adrenoceptor antagonistic potency of MN and NMN. In human adipocytes EPI-3-O-S and NE-3-O-S were 100- to 1000-fold less potent to inhibit lipid mobilization via alpha 2-adrenoceptors as well as to stimulate the beta-adrenoceptor mediated lipolysis when compared with free CA.

Adipose Tissue↗
PubMed2007

Requirement of the C3HC4 zinc RING finger of the Arabidopsis PEX10 for photorespiration and leaf peroxisome contact with chloroplasts.

Plant peroxisomes perform multiple vital metabolic processes including lipid mobilization in oil-storing seeds, photorespiration, and hormone biosynthesis. Peroxisome biogenesis requires the function of peroxin (PEX) proteins, including PEX10, a C(3)HC(4) Zn RING finger peroxisomal membrane protein. Loss of function of PEX10 causes embryo lethality at the heart stage. We investigated the function of PEX10 with conditional sublethal mutants. Four T-DNA insertion lines expressing pex10 with a dysfunctional RING finger were created in an Arabidopsis WT background (DeltaZn plants). They could be normalized by growth in an atmosphere of high CO(2) partial pressure, indicating a defect in photorespiration. beta-Oxidation in mutant glyoxysomes was not affected. However, an abnormal accumulation of the photorespiratory metabolite glyoxylate, a lowered content of carotenoids and chlorophyll a and b, and a decreased quantum yield of photosystem II were detected under normal atmosphere, suggesting impaired leaf peroxisomes. Light and transmission electron microscopy demonstrated leaf peroxisomes of the DeltaZn plants to be more numerous, multilobed, clustered, and not appressed to the chloroplast envelope as in WT. We suggest that inactivation of the RING finger domain in PEX10 has eliminated protein interaction required for attachment of peroxisomes to chloroplasts and movement of metabolites between peroxisomes and chloroplasts.

Amino Acid Sequence↗
PubMed1986

Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells.

Nerve trauma initiates significant changes in the composition of proteins secreted by nonneuronal cells. The most prominent of these proteins is a 37-kDa protein, whose expression correlates with the time course of nerve development, degeneration, and regeneration. We now report that the 37-kDa protein is apolipoprotein E (apoE). We produced a specific antiserum against the 37-kDa protein isolated from previously crushed nerves. This antiserum recognizes a 36-kDa protein in rat serum that we have purified and identified as apoE. The anti-37-kDa antiserum also recognizes apoE on electrophoretic transfer blots of authentic samples of high and very low density lipoproteins. The nerve 37-kDa protein comigrates with apoE by two-dimensional electrophoresis, shares a similar amino acid composition, and reacts with an antiserum against authentic apoE. The purified apoE specifically blocks the immunoprecipitation of [35S]methionine-labeled 37-kDa protein synthesized by nonneuronal cells. Thus, on the basis of its molecular mass, isoelectric point, amino acid composition, and immunological properties, we conclude that the 37-kDa protein is apoE. We also used light microscopic immunohistochemistry to localize apoE following nerve injury. In rats with optic nerve lesions, the 37-kDa antiserum bound specifically to the degenerating optic tracts and to the retino-recipient layers of the lateral geniculate nucleus and the superior colliculus. We propose that apoE is synthesized by phagocytic cells in response to nerve injury for the purpose of mobilizing lipids produced as a consequence of axon degeneration.

Amino Acids↗
PubMed2001

Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein.

Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.

Cells, Cultured↗
PubMed1997

Hormonal control of regional fat distribution.

Hormones exert powerful influences on body fat distribution in humans. Studies under fully controlled conditions in vitro have indicated that cortisol and insulin facilitate lipid accumulation by expressing lipoprotein lipase (LPL). Growth hormone (GH) abolishes this and turns metabolism towards lipid mobilization. Testosterone and GH inhibit LPL and stimulate lipolysis markedly. Cortisol effects are mediated via a glucocorticoid receptor, and testosterone effects via an androgen receptor, the density of which appears to be higher in visceral than subcutaneous adipose tissue. The receptor-mediated effects are probably expressed via transcription of appropriate genes. The female sex steroids also regulate adipose tissue metabolism, but apparently not directly in the absence of specific cellular receptors. Oestrogens seem to exert net effects similar to those of testosterone. These results of cellular studies agree well with in-vivo studies of triglyceride uptake and turnover in different adipose tissue regions. Furthermore, clinical entities with characteristic disturbances in hormone levels show the expected redistribution patterns.

Adipose Tissue↗