Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism

The term energy metabolism comprises the entirety of chemical processes associated with uptake, conversion, storage, and breakdown of nutrients. All these must be tightly regulated in time and space to ensure metabolic homeostasis in an environment characterized by cycles such as the succession of day and night. Most organisms evolved endogenous circadian clocks to achieve this goal. In mammals, a ubiquitous network of cellular clocks is coordinated by a pacemaker residing in the hypothalamic suprachiasmatic nucleus. Adipocytes harbor their own circadian clocks, and large aspects of adipose physiology are regulated in a circadian manner through transcriptional regulation of clock-controlled genes. White adipose tissue (WAT) stores energy in the form of triglycerides at times of high energy levels that then serve as fuel in times of need. It also functions as an endocrine organ, releasing factors in a circadian manner to regulate food intake and energy turnover in other tissues. Brown adipose tissue (BAT) produces heat through nonshivering thermogenesis, a process also controlled by the circadian clock. We here review how WAT and BAT contribute to the circadian regulation of energy metabolism. We describe how adipose rhythms are regulated by the interplay of systemic signals and local clocks and summarize how adipose-originating circadian factors feed-back on metabolic homeostasis. The role of adipose tissue in the circadian control of metabolism becomes increasingly clear as circadian disruption leads to alterations in adipose tissue regulation, promoting obesity and its sequelae. Stabilizing adipose tissue rhythms, in turn, may help to combat disrupted energy homeostasis and obesity.

Invertebrate Gonadotropin-Releasing Hormone Receptor Signaling and Its Relevant Biological Actions

Gonadotropin-releasing hormones (GnRHs) play pivotal roles in reproduction via the hypothalamus-pituitary-gonad axis (HPG axis) in vertebrates. GnRHs and their receptors (GnRHRs) are also conserved in invertebrates lacking the HPG axis, indicating that invertebrate GnRHs do not serve as “gonadotropin-releasing factors” but, rather, function as neuropeptides that directly regulate target tissues. All vertebrate and urochordate GnRHs comprise 10 amino acids, whereas amphioxus, echinoderm, and protostome GnRH-like peptides are 11- or 12-residue peptides. Intracellular calcium mobilization is the major second messenger for GnRH signaling in cephalochordates, echinoderms, and protostomes, while urochordate GnRHRs also stimulate cAMP production pathways. Moreover, the ligand-specific modulation of signal transduction via heterodimerization between GnRHR paralogs indicates species-specific evolution in Ciona intestinalis. The characterization of authentic or putative invertebrate GnRHRs in various tissues and their in vitro and in vivo activities indicate that invertebrate GnRHs are responsible for the regulation of both reproductive and nonreproductive functions. In this review, we examine our current understanding of and perspectives on the primary sequences, tissue distribution of mRNA expression, signal transduction, and biological functions of invertebrate GnRHs and their receptors.

411 Sperm movement, storage, and release from the oviduct

After semen deposition, a fraction of sperm is transported through the female reproductive tract to the lower oviduct, the isthmus, where sperm are retained to form a reservoir. Some of these sperm are released to move to the upper oviduct, the site of fertilization. For sperm to make this journey, they must overcome challenges including possible phagocytosis, high fluid viscosity, and peristaltic contractions of the tract. The study of sperm transport is complex because so few sperm reach the site of fertilization. We have focused our studies on how sperm are retained in the reservoir, how storage prolongs sperm lifespan, and how sperm are released to fertilize oocytes. Sperm storage is particularly important in situations in which ovulation is not tightly synchronized with semen deposition. This occurs in domestic animals, but is especially notable in some species of bats, birds, and insects. Using porcine sperm and an array of 400 common glycans, we identified two specific glycan motifs found in all structures that bound sperm, a Lewis X trisaccharide and a branched 6-sialylated oligosaccharide. Tandem MS profiling indicated that both motifs were abundant in the asparagine-linked glycans of the oviduct epithelium and several larger oligosaccharides were identified that contained both motifs. When these motifs were immobilized, each could retain sperm, suppress Ca2+ influx and lengthen sperm lifespan. Secretions from the cumulus-oocyte complex (COC) and progesterone released sperm from immobilized oviduct glycans, suggesting that COCs can themselves signal sperm release. Progesterone-induced release required CatSper channels, sperm hyperactivation and was dependent on sperm protein degradation. These studies support a model in which sperm are retained in the isthmus by specific glycans on the epithelium, which extends sperm lifespan until COCs produce releasing factors that promote sperm liberation from the isthmus and movement to the ampulla to fertilize the COCs.

Integrative Analysis Reveals Histone Demethylase LSD1/KDM1A Associates with RNA Polymerase II Pausing

RNA polymerase II (RNAPII) pausing at gene promoters is a rate-limiting step in transcription regulation. Previous studies have elucidated the coordinated actions of pausing and releasing factors that collectively modulate RNAPII pausing. In general, the involvement of chromatin remodellers in RNAPII pausing has not been well documented. Whilst LSD1 is well-known for its role in decommissioning enhancers during ESC differentiation, its role at the promoters of genes remains poorly understood despite their widespread presence at these sites. Here, we report that LSD1 is associated with RNAPII pausing at the promoter-proximal region of genes in mouse embryonic stem cells (ESCs). We demonstrate that the knockdown of LSD1 preferentially affects genes with higher RNAPII pausing than those with lower pausing and, importantly, show that the co-localization of LSD1 and MYC, a factor known to regulate pause-release, is associated with the enrichment of other RNAPII pausing factors compared to their independent counterparts. Moreover, we found that genes co-occupied by LSD1 and MYC are significantly enriched for housekeeping genes that are involved in metabolic processes and globally depleted of transcription factors compared to those bound only by LSD1. These findings reveal a pleiotropic role of LSD1 in regulating housekeeping program besides its previously known role in regulating cell identity programs. Our integrative analysis presents evidence for a previously unanticipated role of LSD1 in RNAPII pausing through its association with pause release factors in modulating cell-type specific and cell-type invariant genes.

Life and Research of V. А. Charkin — scientist, father, grandfather

Charkin Volodymyr was PhD in Biology, Senior researcher, Head of the Laboratory of Cattle Nutrition that focuses on researching the physiology of animal lactation, studying the influence of Iodium, Chromium, Selenium, Cobalt on metabolic processes, productivity and composition of milk; development of elements of national protein feeding system of high productive cows that correspond to modern protein standardizing criteria. Lactation is a complex process of creation, storing and producing milk in animal’s mammal gland. Nervous system and hormones of endocrine glands with the help of brain cortex and hypothalamus, where lactation center is located, regulate the process of mild production. Hypothalamus produces releasing factors – somatoliberin and prolactoliberin that stimulate the production of hormones somatotropin and prolactin in hypothesis. These hormones directly take part in the production of milk. The role of other endocrine glands is that they contribute to promotion of the synthesis of milk precursors and increase of their amount in blood.

Releasing factors of diabetes mellitus

In order to establish a link between staple foods and prevalence of diabetes in populations, a preliminary survey aiming at diabetes frequencies has been executed with 16 diabetics. Glycaemia was evaluated in clinical laboratory and survey slip was used to collect information from patients. Results were analyzed at a threshold a = 0.05 with XLSTAT. Frequencies of higher glycaemia in diabetics for staple food were found in this ranking order: rice > sorghum > wheat > maize > millet > others. Such foods were eaten during a long period before diabetes symptoms. Patients of 36-40 years old were numerous in proportion (31.25%). Others cases of age groups go from 0.0% to 6.25% frequencies. Type 1 diabetes is found in sedentary persons and sellers with positive and significant correlation with glycaemia over 1.25 g/L (r =0.785-0.850) because of consummation of sorghum (r = 0.755) and wheat (r = 0.674) for social reason (r = 0.738). Type 2 diabetes is linked to economic reason (r = 0.688). Only cultivators have glycaemia between 1 g/L and 1.25 g/L. Contrary, sedentary, salaried and seller people showed glycaemia over 1.25 g/L. Consequently, significant correlations indicate wheat (r =0.851), rice (r = 0.815), sorghum (r = 0.753), maize (r = 0.655) and tea (r = 0.646); all are correlated social reasons (r = 0.825). Thus, many factors especially foods and life system contribute in releasing diabetes.

Principles of hormone action

Hormones, produced by glands or cells, are messengers which act locally or at a distance to coordinate the function of cells and organs. Types of hormone include: peptides (e.g. hypothalamic releasing factors) and proteins (e.g. insulin, growth hormone)—these generally interact with membrane receptors located on the cell surface, causing activation of downstream signalling pathways leading to alteration in gene transcription or modulation of biochemical pathways to effect a physiological response; steroids (e.g. cortisol, progesterone, testosterone, oestradiol) and other lipophilic substances (e.g. vitamin D, retinoic acid, thyroid hormone)—these act by crossing the plasma membrane to interact with intracellular receptors, with hormone action via nuclear receptors altering cellular gene expression directly.

TCTP from Loxosceles Intermedia (Brown Spider) Venom Contributes to the Allergic and Inflammatory Response of Cutaneous Loxoscelism

LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic effect of TCTP is related to its pro-inflammatory functions. An initial characterization of LiTCTP in animal models showed that this toxin can increase the microvascular permeability of skin vessels and induce paw edema in a dose-dependent manner. We evaluated the role of LiTCTP in vitro and in vivo in the inflammatory and allergic aspects that undergo the biological responses observed in Loxoscelism, the clinical condition after an accident with Loxosceles spiders. Our results showed LiTCTP recombinant toxin (LiRecTCTP) as an essential synergistic factor for the dermonecrotic toxin actions (LiRecDT1, known as the main toxin in the pathophysiology of Loxoscelism), revealing its contribution to the exacerbated inflammatory response clinically observed in envenomated patients.