Processing of pro-vitellogenin in insect fat body: a role for high-mannose oligosaccharide

Several discrete events were resolved in the processing of vitellogenin in Blattella germanica. Using tunicamycin to inhibit the synthesis of high-mannose oligosaccharide, a high molecular weight pro-vitellogenin peptide (apo-proVG, Mr 215,000) was identified in fat body. Dosages of tunicamycin which inhibited glycosylation of vitellogenin by 98% inhibited its synthesis by as much as 59%, yet led to an intracellular accumulation of apo-proVG. Reversibility and dose dependency of these effects on vitellogenin synthesis, glycosylation, proteolytic processing, and secretion were demonstrated. In control insects, glycosylation of apo-proVG yielded a Mr 240,000 pro-vitellogenin peptide (proVG). FITC-Concanavalin A bound to purified proVG but not to apo-proVG, thus confirming an absence of high-mannose oligosaccharide in the apo-protein. Following its glycosylation, proVG was processed rapidly in fat body to Mr 160,000 (VG160) and Mr 102,000 (VG102) peptides which subsequently were secreted into hemolymph. After uptake into developing oocytes, the VG160 peptide was processed further prior to chorionation, yielding subunits of Mr 95,000 and 50,000. Uniqueness of the peptides of mature vitellin (Mr 102,000, 95,000, and 50,000) was indicated by comparison of the CNBr fragments of each purified subunit. Staining of CNBr fragments with FITC-Concanavalin A also indicated that high-mannose oligosaccharides are attached at one or more sites within each vitellin subunit. Resolution of the substructure of this insect vitellin and identification of events involved in the processing and secretion of its fat body apo-protein provide a basis for further study of the assembly and transport of vitellogenin, its packaging in eggs, and utilization during embryogenesis.     

The role of body fat in female attractiveness

The purpose of the present study was to investigate the role of body fat percentage (BF%) on female attractiveness. To this end, a series of female body images were selected from a collection of dual-energy X-ray absorptiometry scans. Images were stratified by three levels (low, mid, and high) of waist-to-hip ratio (WHR) and seven levels (15%–50%) of BF%. These 21 images were presented in a random order and rated for attractiveness. Results indicate that WHR, BMI, and BF% are all significant predictors of female attractiveness when regressed separately (R²= 0.19, 0.70, and 0.76, respectively). When regressed simultaneously, all three variables accounted for 87% of the variance in image attractiveness, with only BF% and WHR being significant predictors. Further analysis revealed that body fat might disrupt the negative linear relationship between WHR and attractiveness. Men and women differed significantly in most categories of WHR and BF%, with men generally rating images as less attractive than women. These data indicate that BF% appears to be a strong cue for attractiveness and that the impact of WHR and BMI on attractiveness is dependent, in part, on BF%. The appearance of body fat may provide disruption in the visual cues of both shape and size of the female body, potentially impacting behavior.     

Leptin regulates energetic tradeoffs between body fat and humoural immunity

Mounting an immune response requires a relatively substantial investment of energy and marked reductions in energy availability can suppress immune function and presumably increase disease susceptibility. We have previously demonstrated that a moderate reduction in energy stores via partial surgical lipectomy (LIPx) impairs humoural immunity of Siberian hamsters (Phodopus sungorus). Here we tested the hypothesis that LIPx-induced decreases in immunity are mediated by changes in the adipose tissue hormone leptin. Hamsters received bilateral surgical removal of inguinal white adipose tissue (IWATx) or sham surgeries (Sham). Half the animals in each group received osmotic minipumps containing murine leptin (0.5mulh-1 for 10 days) whereas the remaining animals received minipumps containing vehicle alone; all animals were subsequently challenged with the novel antigen keyhole limpet haemocyanin (KLH). In general, serum leptin and anti-KLH antibodies were significantly correlated with one another with higher levels generally indicating enhanced immunity. In addition, IWATx hamsters had significantly lower serum anti-KLH IgG compared with sham animals. Exogenous leptin, however, attenuated LIPx-induced immune suppression but did not affect humoural immunity in sham animals. These results suggest that reductions in energy availability lead to impairments in humoural immunity and that leptin can serve as a neuroendocrine signal between body fat and immunity regulating humoural immune responses.     

Obesity genes and the regulation of body fat content

Physiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte-stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity.     

The role of serotonergic system in body temperature regulation.

Results indicate that vascular responses to temperature stimulation are predominantly impaired in animals with 5-HT deprivation. A hypothesis is therefore raised that the 5-HT system participates in body temperature regulation in such a way as to link the regulatory output with vasomotor pathways. The 5-HT system in the spinal cord has been shown to inhibit the afferent transmission of temperature signals. Therefore, depletion of 5-HT does not prevent sensory transmission, at least at the spinal cord level.     

Rubisco regulation: a role for inhibitors

In photosynthesis Rubisco catalyses the assimilation of CO(2) by the carboxylation of ribulose-1,5-bisphosphate. However, the catalytic properties of Rubisco are not optimal for current or projected environments and limit the efficiency of photosynthesis. Rubisco activity is highly regulated in response to short-term fluctuations in the environment, although such regulation may not be optimally poised for crop productivity. The regulation of Rubisco activity in higher plants is reviewed here, including the role of Rubisco activase, tight binding inhibitors, and the impact of abiotic stress upon them.     

The source of lipids and polyphenols for the insect cuticle: The role of fat body, oenocytes and oenocytoids

The newly fed fourth instar larva of Rhodnius lays down the outer epicuticle at 8-9 days, the inner epicuticle at 9 days, and it moults at 12 days. The oenocytes, which supply the lipid precursors, reach their maximum size at 7 days when lipid spheres and lipid-coated vesicles appear in their cytoplasm. The epidermal cells extend cytoplasmic strands to the contracting oenocytes and receive abundant lipid, which they transfer to the plasma membrane for construction of the outer and inner epicuticle. The oenocytes also transfer lipid to the epidermis attached to the basal lamina. This lipid is discharged through the lamina and taken up by ocnocytoids. which apply themselves to the basal lamina and liberate this copious absorbed material into the haemolymph before disintegrating. The synthesis of polyphenols for sclerotization takes place in the fat body, reaching a peak at day 10. After discharge into the haemolymph it is taken (presumably by a carrier protein) to the epidermis, where its uptake and transfer can be monitored by argentaffin staining. The tubular system of pore canals and tubular filaments is formed by invagination of the plasma membrane immediately after the inner epicuticle is complete, and is filled with lipid precursors and polyphenols. There is evidence that these metabolites are carried separately: the lipid in multiple tubular filaments; the polyphenol through the substance of the axial filament. Lipid and polyphenols are still supplied to the epidermis during days 10-12. Both are most richly supplied to the sites forming exocuticle-which illustrates the importance of lipid as well as polyphenol in cuticle hardening.     

The role of fat body in testicular spermatogenesis and steroidogenesis inRana hexadactyla lesson

The fat body appears to contribute cholesterol for testicular steroidogenesis. It also appears to provide prostaglandins and cyclic AMP for testicular steroidogenesis since fatectomy impairs this process which is corrected by the addition of prostaglandins and cyclic AMP. Of the two, prostaglandins have a more important role in spermatogenesis and cyclic AMP functions in steroidogenesis These functions of the fat body suggests that it constitutes a link in the hypothalamohypophysial-gonadal axis.     

A role for the adult fat body in Drosophila male courtship behavior

Mating behavior in Drosophila depends critically on the sexual identity of specific regions in the brain, but several studies have identified courtship genes that express products only outside the nervous system. Although these genes are each active in a variety of non-neuronal cell types, they are all prominently expressed in the adult fat body, suggesting an important role for this tissue in behavior. To test its role in male courtship, fat body was feminized using the highly specific Larval serum protein promoter. We report here that the specific feminization of this tissue strongly reduces the competence of males to perform courtship. This effect is limited to the fat body of sexually mature adults as the feminization of larval fat body that normally persists in young adults does not affect mating. We propose that feminization of fat body affects the synthesis of male-specific secreted circulating proteins that influence the central nervous system. In support of this idea, we demonstrate that Takeout, a protein known to influence mating, is present in the hemolymph of adult males but not females and acts as a secreted protein.     

Role and regulation of starvation-induced autophagy in the Drosophila fat body

In response to starvation, eukaryotic cells recover nutrients through autophagy, a lysosomal-mediated process of cytoplasmic degradation. Autophagy is known to be inhibited by TOR signaling, but the mechanisms of autophagy regulation and its role in TOR-mediated cell growth are unclear. Here, we show that signaling through TOR and its upstream regulators PI3K and Rheb is necessary and sufficient to suppress starvation-induced autophagy in the Drosophila fat body. In contrast, TOR's downstream effector S6K promotes rather than suppresses autophagy, suggesting S6K downregulation may limit autophagy during extended starvation. Despite the catabolic potential of autophagy, disruption of conserved components of the autophagic machinery, including ATG1 and ATG5, does not restore growth to TOR mutant cells. Instead, inhibition of autophagy enhances TOR mutant phenotypes, including reduced cell size, growth rate, and survival. Thus, in cells lacking TOR, autophagy plays a protective role that is dominant over its potential role as a growth suppressor.     

The role of plasminogen activator in ovulation

The role of plasminogen activator in ovulation was investigated using the inhibitor, trans-aminomethylcyclohexane carboxylic acid (t-AMCHA). In the regular cycle rat, the plasminogen activator activity of the follicles increased from the diestrus to the estrus phase. In the latter phase, a proteolytic enzyme which was not inhibited by t-AMCHA appeared. After ovulation, the plasminogen activator activity decreased. When ovulation was induced in immature rats by pregnant mare serum gonadotrophin and human chorionic gonadotrophin, remarkable fibrinolytic activity appeared in the ovaries immediately before ovulation. When t-AMCHA was given in the ovulation-induced rats, the fibrinolytic activity of the ovaries was suppressed, the number of ovulated ova decreased and the timing of ovulation was delayed. When t-AMCHA solution was given to rats in the proestrus phase, ovulation was almost completely suppressed, but aprotinin solution exerted no effect on ovulation. These results suggest that plasminogen activator is a key enzyme in ovulation, and that the chain reaction from plasminogen activator to proteolytic enzyme (including collagenase) is of greater importance than that of plasminogen activator to plasmin.     

Genetic variation in brown fat activity and body weight regulation in mice: Lessons for human studies

The recent characterization of brown fat in humans has generated much excitement on the possibility that increased energy expenditure by heat production by this tissue will be able to reduce obesity. This expectation has largely been stimulated by studies with mice that show strong associations between increased brown fat activity and reductions in obesity and insulin resistance. Research in the mouse has been largely based upon the induction or suppression of brown fat and mitochondrial uncoupling protein by genetic methods. The review of this research literature underscores the idea that reductions in obesity in mice are secondary to the primary role of brown adipose tissue in the regulation of body temperature. Given that the variation in brown fat in humans, as detected by PET imaging, is highly associated with administration of adrenergic agonists and reductions in ambient temperature, the effects on obesity in humans may also be secondary to the regulation of body temperature. Induction of thermogenesis by reduced ambient temperature now becomes like muscle and physical activity, another natural method of increased energy expenditure to combat obesity. Furthermore, there is no evidence to indicate that heat production by adrenergic stimulation via cold exposure or drug treatment or the enriched physical environment is restricted to the thermogenic activity of the brown adipocyte.This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.     

A role for pancreatic polypeptide in feeding and body weight regulation

PP administration induces negative energy balance by suppressing food intake and gastric emptying while increasing energy expenditure in rodents. The mechanism of PP actions involves the changes in the expression of hypothalamic feeding-regulatory peptides and the activity of the vago-vagal and vago-sympathetic reflex arc. PP-overexpressing mice we developed exhibited the thin phenotype with decreased food intake and gastric emptying rate. Plasma cholecystokinin (CCK) concentrations were increased in the transgenic mice and CCK-1 receptor antagonist improved the anorexia of the animals. These results, together with the previous notion of PP as an anti-CCK hormone in pancreatic exocrine secretion and gallbladder contraction, indicate that PP-CCK interactions may be either antagonistic or synergistic and the transgenic mice may exhibit the mixed phenotype by overproduction of PP and CCK.     

Impact of resistant starch on body fat patterning and central appetite regulation

Background

Adipose tissue patterning has a major influence on the risk of developing chronic disease. Environmental influences on both body fat patterning and appetite regulation are not fully understood. This study was performed to investigate the impact of resistant starch (RS) on adipose tissue deposition and central regulation of appetite in mice.

Methodology and Principle Findings

Forty mice were randomised to a diet supplemented with either the high resistant starch (HRS), or the readily digestible starch (LRS). Using ¹H magnetic resonance (MR) methods, whole body adiposity, intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured. Manganese-enhanced MRI (MEMRI) was used to investigate neuronal activity in hypothalamic regions involved in appetite control when fed ad libitum. At the end of the interventional period, adipocytes were isolated from epididymal adipose tissue and fasting plasma collected for hormonal and adipokine measurement. Mice on the HRS and LRS diet had similar body weights although total body adiposity, subcutaneous and visceral fat, IHCL, plasma leptin, plasma adiponectin plasma insulin/glucose ratios was significantly greater in the latter group. Adipocytes isolated from the LRS group were significantly larger and had lower insulin-stimulated glucose uptake. MEMRI data obtained from the ventromedial and paraventricular hypothalamic nuclei suggests a satiating effect of the HRS diet despite a lower energy intake.

Conclusion and Significance

Dietary RS significantly impacts on adipose tissue patterning, adipocyte morphology and metabolism, glucose and insulin metabolism, as well as affecting appetite regulation, supported by changes in neuronal activity in hypothalamic appetite regulation centres which are suggestive of satiation.     

The role of syndecans in the regulation of body weight and synaptic plasticity

Body weight is tightly regulated by a feedback mechanism involving peripheral adiposity signals and multiple central nervous system neurotransmitter pathways. Despite the tight regulation of body weight there is an increase in the prevalence of obesity and overweight in Western society. Obesity and overweight are conditions of excess body weight stored as fat. Syndecan-3, a member of the syndecan family of type I transmembrane heparan sulfate proteoglycans is a novel a regulator of feeding behavior and body weight. Syndecans are extracellular matrix molecules (ECMs) that modulate cell adhesion, cell-cell interactions and ligand-receptor interactions. The finding that syndecan-3 can regulate body weight is novel and provides a unique link between the extracellular matrix and body weight regulatory mechanisms. Uniquely, hormones such as leptin previously thought only to regulate body weight by modulating neuropeptide levels, have now been demonstrated to regulate neuronal plasticity in the hypothalamus. ECMs and syndecans have long been recognized as regulators of plasticity. Therefore, this review will focus on highlighting the role of syndecans and in particular syndecan-3 in neuronal development and synaptic organization and how these processes may integrate body weight regulation. As part of this review, we will highlight how syndecan-3 can mediate the activity of adiposity signals, such as leptin, and facilitate changes in neuronal plasticity.     

The role of glypican-3 in the regulation of body size and cancer

Glypicans are a family of heparan sulfate proteoglycans whose members are bound to the cell surface by a glycosylphosphatidylinositol (GPI) anchor. Loss-of-function mutations in GPC3, one of the six mammalian glypicans, causes the Simson-Golabi-Behmel Syndrome. This is a disorder characterized by pre- and post-natal overgrowth, a broad spectrum of visceral and skeletal abnormalities, and an increased risk for the development of embryonic tumors. GPC3-null mice also display significant overgrowth. We have recently reported that GPC3 acts as a negative regulator of Hedgehog signaling during development, and that the overgrowth caused by the lack of functional GPC3 is due, at least in part, to the hyperactivation of Hedgehog signaling. Here we discuss the rationale that led us to hypothesize that GPC3 could be a negative regulator of Hedgehog signaling, and speculate about the implications of our discovery regarding the role of GPC3 in some cancer types. We also discuss our recent results of experiments that investigated the role of the core protein, the heparan sulfate chains, and the GPI anchor in GPC3 function. Finally, we propose an explanation for the tissue-specific function of GPC3.     

Regional fat aspiration for body contouring

Our experience with the original suction lipectomy is presented. The fat removal, done with a specially designed suction tube, is performed layerwise, creating a continuous, regular cavity that is transformed into a virtual space by compressive dressings. The main indication being excessive peritrochanteric fat pads, the operation is done under either epidural or general anesthesia. No antibiotics or anticoagulants are administered, and the patients are mobilized as soon as fully awake. Practicing suction-assisted lipectomy for more than seven years, we have never observed an infection, thrombosis, or fat embolism. In experienced hands, good results can be expected in about 80 percent of patients. Complications are almost always of an aesthetic nature as a result of bad indications. The method is not a surgical treatment for severe obesity.