Role of Some Hormones in Protein Sparing Action of Dietary Fat

Feeding rats with a fat meal caused marked reduction in the level of plasma urea and urinary output of urea and total nitrogen. Experiments were carried out to examine the possible intervention of some hormones in these phenomena. Protein sparing action of fat was exerted even in the alloxan-diabetic, adrenalectomized, hypophysectomized and thyroidectomized rats. Feeding rats with a fat meal caused no appreciable change in the level of cyclic AMP in liver and gastrocnemius muscle. The overall results obtained here are through! to suggest that the action of fat may be exerted independently of any hormones examined; insulin, glucocorticoids, cyclic AMP and other hormones excreted from adrenal, hypophysis and thyroid gland.     

Hormonal regulation of energy metabolism in insects as a driving force for performance

Since all life processes depend on energy, the endocrine control of energy metabolism is one of the driving forces for the performance of an individual. Here, we review the literature on the key players in the endocrine regulation of energy homeostasis in insects, the adipokinetic hormones. These pleiotropic peptides not only control dynamic performance traits (flight, swimming, walking) but also regulatory performance traits (egg production, larval growth, and molting). Adipokinetic hormone is released into the hemolymph during intense muscular activity (flight) and also during apparently less energy-demanding locomotory activities, such as swimming and even walking, and, finally, activates the catabolic enzymes phosphorylase and/or triacylglycerol lipase that mobilize carbohydrates and/or lipids and proline, respectively. At the same time, anabolic processes such as the synthesis of protein, lipid, and glycogen are inhibited. Furthermore, adipokinetic hormones affect locomotory activity via neuromodulatory mechanisms that apparently employ biogenic amines. During oogenesis, it is thought that adipokinetic hormone performs similar tasks, because energetic substrates have to be mobilized and transported from the fat body to the ovaries in order to support oocyte growth. Inhibition of anabolic processes by exogenous adipokinetic hormone results in females that lay fewer and smaller eggs. Much less is known about the role of adipokinetic hormones during larval development and during molting but in this case energy homeostasis has to be tightly regulated as well: in general, during the early phase of a larval instar intake of food prevails and the energy stores of the fat body are established, whereas, prior to the molt, insects stop feeding and mobilize energy stores in the fat body, thereby fueling energy-demanding processes such as the formation of the new cuticle and the emergence from the old one. From the few data available to date, it is clear that adipokinetic hormones are involved in the regulation of these events in larvae.     

Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormones

Sex differences in skeletal muscle regeneration are controversial; comparisons of regenerative events between sexes have not been rigorously defined in severe injury models. We comprehensively quantified inflammation and muscle regeneration between sexes and manipulated sex-specific hormones to determine effects on regeneration. Cardiotoxin injury was induced in intact, castrated and ovariectomized female and male mice; ovariectomized mice were replaced with low- or high-dose 17-β estradiol (E(2)) or progesterone (P4). Extent of injury was comparable between intact mice, but females were more efficient in removal of necrotic debris, despite similar tissue levels of inflammatory cells and chemokines. Myofiber size during regeneration was equivalent between intact mice and after castration or ovariectomy (OVX) but was decreased (P < 0.001) in ovariectomized mice with high-dose E(2) replacement. Intermuscular adipocytes were absent in uninjured muscle, whereas adipocyte area was increased among regenerated myofibers in all groups. Interestingly, intermuscular fat was greater (P = 0.03) in intact females at day 14 compared with intact males. Furthermore, castration increased (P = 0.01) and OVX decreased adipocyte accumulation. After OVX, E(2), but not P4, replacement decreased (P ≤ 0.03) fat accumulation. In conclusion, sex-dependent differences in regeneration consisted of more efficient removal of necrosis and increased fat deposition in females with similar injury, inflammation, and regenerated myofiber size; high-dose E(2) decreased myofiber size and fat deposition. Adipocyte accumulation in regenerating muscle was influenced by sex-specific hormones. Recovery following muscle injury was different between males and females, and sex-specific hormones contributed to these differences, suggesting that sex-specific treatments could be beneficial after injury.     

Effects of soybean isoflavones, probiotics, and their interactions on lipid metabolism and endocrine system in an animal model of obesity and diabetes

The effects of soybean isoflavones with or without probiotics on tissue fat deposition, plasma cholesterol, and steroid and thyroid hormones were studied in SHR/N-cp rats, an animal model of obesity, and were compared to lean phenotype. We tested the hypothesis that probiotics by promoting the conversion of isoflavone glycosides to their metabolically active aglycone form will have a synergistic effect on body fat, cholesterol metabolism, and the endocrine system. Obese and lean SHR/N-cp rats were fed AIN-93 diets containing 0.1% soy isoflavone mixture, 0.1% probiotic mixture, or both together. Different fat tissues were teased and weighed. Plasma was analyzed for cholesterol and steroid and thyroid hormones. In both phenotypes, isoflavones lowered fat deposition in several fat depots. Probiotics alone had no significant effect on fat depots. Isoflavones lowered total, LDL, and HDL cholesterol in lean rats, but in obese rats isoflavones lowered only total and LDL cholesterol. Isoflavones also lowered many of the steroid hormones involved in lipid metabolism but had no significant effect on thyroid hormones. Probiotics had no significant effect on cholesterol or hormones. Thus, our data show that soy isoflavones also lower plasma cholesterol and that this hypocholesterolemic effect appears to be due in part to the modulation of steroid hormones. Probiotics do not seem to enhance the effect of isoflavones.     

Factors conducive to increased protein feeding by the blowfly Phormia regina

ABSTRACT. Each period of elevated protein consumption by Phormia regina was associated with some recognizable physiological event that requires protein synthesis (e.g. tanning, adult fat body development, vitellogenesis). Injecting cycloheximide to inhibit protein synthesis prior to the onset of such events delayed the events and also the development of the associated periods of protein hunger. Injecting cycloheximide after a known period of protein synthesis had occurred, however, did not postpone the normally associated protein hunger even while the inhibitor was fully active. The findings conform to a hypothesis that an unidentified deficit, created by protein synthesis, underlies the tendency by Phormia to increase its ingestion of proteinaceous materials. The effects which different hormones have on protein hunger are evidently indirect results of their control of different periods of protein synthesis.     

Historical perspectives in fat cell biology: the fat cell as a model for the investigation of hormonal and metabolic pathways

For many years, there was little interest in the biochemistry or physiology of adipose tissue. It is now well recognized that adipocytes play an important dynamic role in metabolic regulation. They are able to sense metabolic states via their ability to perceive a large number of nervous and hormonal signals. They are also able to produce hormones, called adipokines, that affect nutrient intake, metabolism and energy expenditure. The report by Rodbell in 1964 that intact fat cells can be obtained by collagenase digestion of adipose tissue revolutionized studies on the hormonal regulation and metabolism of the fat cell. In the context of the advent of systems biology in the field of cell biology, the present seems an appropriate time to look back at the global contribution of the fat cell to cell biology knowledge. This review focuses on the very early approaches that used the fat cell as a tool to discover and understand various cellular mechanisms. Attention essentially focuses on the early investigations revealing the major contribution of mature fat cells and also fat cells originating from adipose cell lines to the discovery of major events related to hormone action (hormone receptors and transduction pathways involved in hormonal signaling) and mechanisms involved in metabolite processing (hexose uptake and uptake, storage, and efflux of fatty acids). Dormant preadipocytes exist in the stroma-vascular fraction of the adipose tissue of rodents and humans; cell culture systems have proven to be valuable models for the study of the processes involved in the formation of new fat cells. Finally, more recent insights into adipocyte secretion, a completely new role with major metabolic impact, are also briefly summarized.     

Weaning and metabolic regulation in the rat

Premature weaning of rats to high carbohydrate diets causes a variety of short- and long-term changes in lipid metabolism, but the mechanisms involved are unclear. It is likely that interaction of diet with certain emerging hormonal control patterns during weaning might condition metabolic control and (or) subsequent adaptations in the adult organism. This implies that the adaptive responses of infant animals to diet may differ from those of the mature organism. For example, premature weaning leads to early appearance of rat liver malic enzyme (ME), even when fat supplies as much as 65% of the dietary energy; the same diet suppresses ME activity in 45-day-old rats. The levels of plasma glucagon and thyroid hormones are elevated during the weaning period. Several studies have shown that triiodothyronine evokes hepatic ME in suckling rats. Conversely, glucagon infusion into prematurely weaned rats suppresses the early appearance of the enzyme. Premature weaning, regardless of fat intake, leads to a rapid decline in plasma glucagon levels. Since glucagon is known to antagonize the actions of triiodothyronine on liver ME, the interaction of diet with glucagon and thyroid hormones is conceivably part of the mechanism responsible for the early appearance of hepatic malic enzyme, whereby the decline of plasma glucagon permits triiodothyronine to act on liver ME. Insulin probably exerts a permissive action subsequently. The manner in which these events relate to the long-term consequences of premature weaning is unknown.     

Seasonal adiposity, correlative changes in metabolic factors and unique reproductive activity in a vespertilionid bat, Scotophilus heathi

The aim of this study was to determine the effect of changes in body mass, fat reserves and feeding activity on circulating levels of lipids, glucose, protein and metabolic hormones in a vespertilionid bat, Scotophilus heathi. Furthermore, the relationship between changes in metabolic factors and hormones with the unique reproductive features of female S. heathi was also examined. The results of this study showed annual variation in body mass, fat reserve and feeding activity, which correlated significantly with circulating levels of lipids, protein and metabolic hormones. Increased corticosterone level during September-October in S. heathi promotes increased feeding activity, which in turn induces hyperinsulinemia in S. heathi during November. Hyperinsulinemia together with low body temperature in November facilitates fat accumulation in bat. Coinciding with the period of fat accumulation raises serum leptin level, which has been demonstrated to suppress ovarian activities thus causing delayed ovulation in S. heathi. Circulating levels of lipids were high during winter dormancy, which may provide energy to stored sperms. The study thus suggests that the unique reproductive features of female vespertilionid bat are strongly linked to fat deposition. J. Exp. Zool. 309A:94-110, 2008. (c) 2008 Wiley-Liss, Inc.     

Regulation of glucose transport by insulin: traffic control of GLUT4

Despite daily fasting and feeding, plasma glucose levels are normally maintained within a narrow range owing to the hormones insulin and glucagon. Insulin increases glucose uptake into fat and muscle cells through the regulated trafficking of vesicles that contain glucose transporter type 4 (GLUT4). New insights into insulin signalling reveal that phosphorylation events initiated by the insulin receptor regulate key GLUT4 trafficking proteins, including small GTPases, tethering complexes and the vesicle fusion machinery. These proteins, in turn, control GLUT4 movement through the endosomal system, formation and retention of specialized GLUT4 storage vesicles and targeted exocytosis of these vesicles. Understanding these processes may help to explain the development of insulin resistance in type 2 diabetes and provide new potential therapeutic targets.     

Serum Leptin in Elderly People: Associations with Sex Hormones,Insulin, and Adipose Tissue Volumes

BAUMGARTNER, RICHARD N., ROBERT R. ROSS, DEBRA L. WATERS, WILLIAM M. BROOKS, JOHN E. MORLEY, GEORGE D. MONTOYA, AND PHILIP J. GARRY. Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes Res. Objective There are few data for associations of serum leptin with body fat, fat distribution, sex hormones, or fasting insulin in elderly adults. We hypothesized that the sex difference in serum leptin concentrations would disappear after adjustment for subcutaneous, but not visceral body fat. Serum leptin would not be associated with sex hormone concentrations or serum fasting insulin after adjusting for body fat and fat distribution. Research Methods and Procedures Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured using magnetic resonance imaging in a cross-sectional sample of 56 nondiabetic, elderly men and women aged 64 years to 94 years. Serum leptin, sex hormones (testosterone and estrone), sex hormone-binding globulin, and fasting insulin were also measured. Nine women were taking hormone replacement, and five men were clinically hypogonadal. Results Leptin was significantly associated with both SAT and VAT in each sex. Adjustment for SAT reduced the sex difference in leptin by 56%, but adjustment for VAT increased the difference by 25%. Leptin was not associated with serum estrone or hormone replacement therapy in the women, but had a significant, negative association with testosterone in the men that was independent of SAT, but not VAT. Leptin was significantly associated with fasting insulin in both sexes independent of age, sex hormones, sex hormone-binding globulin, VAT and SAT. Discussion Sex difference in serum leptin is partly explained by different amounts of SAT. Studies including both men and women should adjust for SAT rather than total body fat that includes VAT. The sex difference in serum leptin is not due to estrogen, but may be partly explained by testosterone. Testosterone is negatively associated with leptin in men, but the association is confounded with VAT. Leptin is associated with fasting insulin in non-diabetic elderly men and women independent of body fat, fat distribution. or sex hormones.     

Regulation and functional relevance of milk fat globules and their components in the mammary gland

Mammary gland and epithelial cells are unique to mammals and are under the control of lactogenic hormones such as prolactin. Recent findings indicated that major components of milk fat globule membrane (MFGM) are under the control of lactogenic hormones, and that the major components butyrophilin and xanthine oxidoreductase are indispensable for milk fat secretion. Further, prolactin signaling is negatively controlled by two highly related protein tyrosine phosphatases, PTP1B and TC-PTP. Milk fat globule EGF factor 8 (MFG-E8) is one of the major components of MFGM and is upregulated during lactation. MFG-E8 is further upregulated in the involuting mammary gland. MFG-E8 on exosome-like membrane vesicles in the milk recovered from post-weaning but not lactating mammary glands exhibits higher binding activity to phosphatidylserine and apoptotic mammary epithelial cells, and serves as a link between apoptotic mammary epithelial cells and phagocytes. Recent reports using MFG-E8 deficient mice support the view that MFG-E8 is indispensable for eliminating apoptotic mammary epithelial cells during involution.     

Cyclic AMP in locust fat body: Correlation with octopamine and adipokinetic hormones during flight

The effects of flight upon the level of cyclic AMP in the fat body of Locusta migratoria have been examined. Flight induced two phases of cyclic AMP elevation; the first during the initial 10 min of flight, the second between 20–30 min of flight. Neck-ligated locusts have increased levels of cyclic AMP after 10 min of flight, indicating that the adipokinetic hormones are not necessary for this elevation. Injection of 6 mg trehalose, a procedure known to delay the release of adipokinetic hormones, prevented the increases seen at 10 and 30 min of flight. Injection of synthetic adipokinetic hormone I increased the levels of cyclic AMP within 5 min, and these were maintained for up to 15 min. The roles of octopamine and the adipokinetic hormones in increasing fat body cyclic AMP, and thereby regulating haemolymph lipid, during flight are discussed.     

Applications of hormones in the metabolic regulation of growth and lactation in ruminants

Exogenous natural and synthetic estrogenic and androgenic steroid hormones are used commercially to stimulate metabolic processes associated with increased rate and efficiency of body growth in ruminants. However, mechanisms of action of steroid hormone-induced effects on metabolism are relatively unknown. Application of peptide hormones to muscle growth, fat deposition, and lactation has lagged because of lack of sufficient quantities of the hormones. However, with recombinant DNA technology synthesis of large quantities of peptide hormones is now feasible. Most efforts have focused on growth hormone (GH), growth hormone-releasing factor (GRF), and prolactin (PRL) effects on lactation. For example, administration of GH or GRF stimulates yields of milk, milk fat, protein, and lactose as much as 41% in cattle. The mechanism of GH action probably involves somatomedin C acting at extramammary sites and (or) directly at the mammary cell. PRL is lactogenic but has no significant effect on established lactation in cattle. Daily exposure of cattle to 16 h light and 8 h of darkness stimulates milk yield and body growth and reduces fat accretion in the carcass, but the hormonal signals responsible for these photoperiod-induced responses are unknown. Photoperiod manipulations are relatively easy to apply to ruminants, but development of suitable delivery systems for animals will greatly enhance application of peptide hormones to further studies of metabolism as well as commercial livestock production systems.     

Glucose metabolism in isolated fat cells: enhanced response of larger adipocytes from older rats to epinephrine and adrenocorticotropin.

The effects of insulin and of two lipolytic hormones (epinephrine and ACTH1) on the rate and pattern of glucose metabolism were compared during incubation of isolated fat cells, obtained from epididymal fat pads of rats of varying age and degrees of adiposity. Glucose metabolism and the intracellular free fatty acid levels were expressed on a per cell basis and in relation to adipocyte size. The data for total glucose metabolism show that, in contrast to the declining insulin effect observed with adipocyte enlargement, the stimulation of glucose uptake and metabolism by these lipolytic hormones was significantly greater in the larger fat cells from the older fatter rats than in the smaller ones from the younger leaner rats. Lipolytic hormones suppressed, whereas insulin enhanced, fatty acid synthesis; moreover the lipolytic hormones stiumlated glucose ce effect of epinephrine on the intracellular free fatty acid levels was greater in the small fat cells than in the large ones; this effect of epinephrine was markedly curtained by the presence of glucose in the incubation medium, making it unlikely that acceleration of glucose metabolism by the lipolytic stimulus was mediated by an elevation of the intracellular free fatty acid level. The present results show a markedly enhanced capacity of the large adipocytes to accelerate glucose metabolism in response to these liplytic hormones. Thus, in contrast to prevailing notions of declining hormonal responsiveness with expanding fat cell size in older and more obese animals, this study documents an instance of increased hormonal response in enlarged adipocytes and points to the need for a more comprehensive reevaluation of the various hormonal effects in adipocytes of different size.     

Integrating hormone signaling and patterning mechanisms in plant development

Plant growth and development are driven by the bustling integration of a vast number of signals, among which plant hormones dominate. Understanding the role of hormones in particular developmental events requires their integration with developmental regulators known to be specific to those events. Using the increasing number of tools that can be utilized to probe hormone biosynthesis, transport and response, several recent studies have taken such an integrative approach, and in so doing have contributed to a clearer picture of precisely how hormones control plant development.     

Activation of triacylglycerol lipase in the fat body of a beetle by adipokinetic hormone

The activation of triacylglycerol lipase and the stimulation of proline synthesis in the fat body of the fruit beetle Pachnoda sinuata by the endogenous octapeptide hormone Melme-CC (pQLNYSPDWa), which belongs to the family of insect adipokinetic hormones, were studied, and the correlation of both events investigated. At rest, the activity of triacylglycerol lipase in the fat body of the beetle was higher than in the fat body of the American cockroach, Periplaneta americana, but lower than in the migratory locust, Locusta migratoria. Triacylglycerol lipase of the beetle is activated by: (a) injection of synthetic Melme-CC and (b) the stimulus of flight. Activation of lipase by Melme-CC is time-dependent. Injection of cpt-cAMP activates triacylglycerol lipase in the fat body and causes an increase in the concentration of proline in the haemolymph at the expense of alanine. In contrast, injection of F-inositol-1,4,5-phosphate does not affect the activation state of lipase, nor the levels of amino acids in the haemolymph. High doses of octopamine do not activate lipase. Furthermore, activity of fat body lipase and proline concentration in the haemolymph both follow a circadian rhythm: both parameters are high in the morning, whereas they are low in the evening. When transfer of Melme-CC, released from the corpora cardiaca, to the thorax/abdomen is prevented by neck-ligation, the activity of lipase, as well as the circulating proline levels are low. Regression analysis revealed that activity of triacylglycerol lipase is positively correlated to proline concentration in the haemolymph, whereas there is a negative correlation of the enzyme activity and alanine level in the haemolymph. From these results we conclude that the activation of fat body triacylglycerol lipase by Melme-CC in P. sinuata stimulates proline synthesis. Proline is one of the major substrates to power flight activity in the beetle.     

Effect of thyroid hormones on acid cholesterol ester hydrolase activity in rat liver,heart and epididymal fat pads

The regulation of acid cholesterol ester hydrolase activity by thyroid hormones was studied in subcellular fractions from rat liver, heart, and epididymal fat pads; hydrolase activity was determined at pH 5 with a glycerol-dispersed cholesterol oleate substrate preparation. Acid cholesterol ester hydrolase activity was decreased in liver preparations from thyroidectomized rats relative to activity in livers from euthyroid control rats. Administration of triidothyronine to either euthyroid or hypothyroid (thyroidectomized) rats resulted in an increase in acid cholesterol ester hydrolase activity in liver preparations. Similar effects of thyroidectomy and the administration of triiodothyronine on acid cholesterol ester hydrolase activity were observed with fat pad preparations. In contrast, no effect of thyroid hormones was observed on acid cholesterol ester hydrolase activity in heart. These results suggest that thyroid hormones may regulate the catabolism of serum lipoproteins, in part, by alterations in lysosomal acid cholesterol ester hydrolase activity in liver and epididymal fat pads.     

Short-term disappearance of muscarinic cell surface receptors in carbachol-induced desensitization

N6-Phenylisopropyladenosine was employed in the absence of endogenous adenosine to explore the influence exerted by the R-site over the antagonistic interaction of insulin and catecholamines on several parameters of fat cell metabolism. When no hormones were present, N6-phenylisopropyladenosine had little or no effect; however, the nucleoside potentiated insulin inhibition of catecholamine-stimulated events, such as lipolysis, and, conversely, diminished or blocked catecholamine inhibition of insulin-stimulated processes, such as 2-deoxyglucose uptake, glucose oxidation and esterification, even under conditions where N6-phenylisopropyladenosine, alone, was ineffective in reversing catecholamine actions.     

Incretin and islet hormonal responses to fat and protein ingestion in healthy men

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet function after carbohydrate ingestion. Whether incretin hormones are of importance for islet function after ingestion of noncarbohydrate macronutrients is not known. This study therefore examined integrated incretin and islet hormone responses to ingestion of pure fat (oleic acid; 0.88 g/kg) or protein (milk and egg protein; 2 g/kg) over 5 h in healthy men, aged 20-25 yr (n=12); plain water ingestion served as control. Both intact (active) and total GLP-1 and GIP levels were determined as was plasma activity of dipeptidyl peptidase-4 (DPP-4). Following water ingestion, glucose, insulin, glucagon, GLP-1, and GIP levels and DPP-4 activity were stable during the 5-h study period. Both fat and protein ingestion increased insulin, glucagon, GIP, and GLP-1 levels without affecting glucose levels or DPP-4 activity. The GLP-1 responses were similar after protein and fat, whereas the early (30 min) GIP response was higher after protein than after fat ingestion (P<0.001). This was associated with sevenfold higher insulin and glucagon responses compared with fat ingestion (both P<0.001). After protein, the early GIP, but not GLP-1, responses correlated to insulin (r(2)=0.86; P=0.0001) but not glucagon responses. In contrast, after fat ingestion, GLP-1 and GIP did not correlate to islet hormones. We conclude that, whereas protein and fat release both incretin and islet hormones, the early GIP secretion after protein ingestion may be of primary importance to islet hormone secretion.     

Regulation of lipogenesis in adipocytes. Independent effects of thyroid hormones, cyclic AMP and insulin on the uptake of deoxy-D-glucose.

Thyroidectomy is known to enhance fat cell phosphodiesterase activity; as a result, the response to lipolytic hormones is markedly reduced. Thyroidectomy also stimulates overall lipogenesis and the uptake of glucose: the present experiments investigated whether there was a correlation between cyclic AMP and glucose uptake. The parameter measured was the transport and phosphorylation (uptake) of deoxy-D-glucose in the presence of two modifiers of the cyclic AMP pool: phosphodiesterase inhibitors and the analogue, dibutyryl cyclic AMP. The inhibition by methylxanthines and dibutyryl cyclic AMP of deoxy-D-glucose uptake observed, was the same in fat cells from normal and thyroidectomized rats: the latter nonetheless still maintained their enhanced glucose uptake. It was therefore concluded that thyroid hormones and cyclic AMP control this step by different, separate pathways. Insulin, well known for its lipogenic effect, enhanced deoxy-D-glucose uptake in fat cells from both normal and thyroidectomized rats to the same extent (about 40%). An additive effect of thyroidectomy and insulin on glucose uptake was thus demonstrated. These results imply that glucose uptake in the adipocyte is controlled by at least three factors: thyroid hormones, cyclic AMP and insulin, each of which can act independently. Maximum glucose uptake is achieved in the presence of a combination of low concentrations of cyclic AMP, of insulin, and in the absence of thyroid hormones.