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Symbiotic dinoflagellates in the family Symbiodiniaceae release mobile compounds (e.g., glucose, glycerol, amino acids, and lipids) to their host's tissues. Little is known about how different symbionts affect quantitative and qualitative differences in these compounds. We tested how symbiont identity affects glycerol and glucose pools in the tissues of the sea anemone Exaiptasia pallida ('Aiptasia'). We infected symbiont-free anemones with three different symbiotic dinoflagellates: Breviolum minutum isolated from our Aiptasia stock, B. minutum isolated from a different Aiptasia population, and the free-living Effrenium voralum. We measured free glycerol and glucose levels in host tissues under photosynthetic conditions, as well as metabolite release by these algae when freshly isolated from Aiptasia and incubated in a host tissue homogenate. Anemone tissues containing the stock B. minutum accumulated glycerol at a higher symbiont cell-specific rate than those containing the alternative B. minutum or E. voratum (e.g., at 9 h of light incubation: stock B. minutum, 4.05 * [10.sup.-5] nmol per algal cell; alternative B. minutum, 0.90 * [10.sup.-5] nmol per algal cell; E. voratum: 1.14 * [10.sup.-5] nmol per algal cell). All symbiotic hosts accumulated glucose between 1 and 12 h of light incubation. At 12 h, the symbiont cell-specific glucose content was 6-fold higher in anemone tissues that contained stock B. minutum than in those containing the alternative B. minutum (1.73 * [10.sup.-6] vs. 0.30 * [10.sup.-6] nmol per algal cell, respectively). All freshly isolated algae released glycerol and glucose when incubated in host homogenate except E. voratum, which did not release glycerol. These trends mirrored those in hospite. Our results suggest that, on an algal cell-specific basis, B. minutum isolated from the same Aiptasia stock provided better nutritional support to the host than did the two other algae, though this was not reflected in colonization success, highlighting the underlying complexity of host-symbiont recognition and symbiosis establishment in the cnidariandinoflagellate partnership., Introduction Many cnidarians (e.g., corals, sea anemones) form symbioses with dinoflagellates in the family Symbiodiniaceae. This family is characterized by considerable genetic diversity, with multiple genera and species now recognized [...]

BACKGROUND. Postreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g., insulin receptor pathogenic variants, INSR) causes hyperglycemia without steatosis. We examined 4 pathologic conditions of IR in humans to examine pathways controlling lipid metabolism and gluconeogenesis. METHODS. Cross-sectional study of severe receptor IR (INSR, n = 7) versus postreceptor IR that was severe (lipodystrophy, n = 14), moderate (type 2 diabetes, n = 9), or mild (obesity, n = 8). Lipolysis (glycerol turnover), hepatic glucose production (HGP), gluconeogenesis (deuterium incorporation from body water into glucose), hepatic triglyceride (magnetic resonance spectroscopy), and hepatic fat oxidation (plasma [beta]-hydroxybutyrate) were measured. RESULTS. Lipolysis was 2- to 3-fold higher in INSR versus all other groups, and HGP was 2-fold higher in INSR and lipodystrophy versus type 2 diabetes and obesity (P < 0.001), suggesting severe adipose and hepatic IR. INSR subjects had a higher contribution of gluconeogenesis to HGP, approximately 77%, versus 52% to 59% in other groups (P = 0.0001). Despite high lipolysis, INSR subjects had low hepatic triglycerides (0.5% [interquartile range 0.1%-0.5%]), in contrast to lipodystrophy (10.6% [interquartile range 2.8%-17.1%], P < 0.0001). [beta]-hydroxybutyrate was 2- to 7-fold higher in INSR versus all other groups (P < 0.0001), consistent with higher hepatic fat oxidation. CONCLUSION. These data support a key pathogenic role of adipose tissue IR to increase glycerol and FFA availability to the liver in both receptor and postreceptor IR. However, the fate of FFA diverges in these populations. In receptor-level IR, FFA oxidation drives gluconeogenesis rather than being reesterified to triglyceride. In contrast, in postreceptor IR, FFA contributes to both gluconeogenesis and hepatic steatosis. TRIAL REGISTRATION. ClinicalTrials.gov NCT01778556, NCT00001987, and NCT02457897. FUNDING. National Institute of Diabetes and Digestive and Kidney Diseases, US Department of Agriculture/Agricultural Research Service 58-3092-5-001., Introduction Insulin is a hormone that signals the fed state, promoting a switch from net glucose production to net glucose uptake and shifting lipids from lipid metabolism to lipid storage. [...]

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin [D.sub.3] [1,25[(OH).sub.2]D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography-mass spectrometry-based (LC-MS-based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase-mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury., Introduction Fibroblast growth factor-23 (FGF23) levels increase with both acute and chronic kidney disease (CKD) (1) and are a strong independent risk factor for adverse renal outcomes and mortality in [...]

Stanniocalcin-1 and -2 belong to a family of molecules that exhibit both paracrine and autocrine effects in mammalian cells. Human stanniocalcin-1 (hSTC-1) is expressed in a wide range of tissues, including white adipose tissue. In fed rats, hSTC-1 increases carbon flux from glucose to lipids in retroperitoneal white adipose tissue. Human stanniocalcin-2 (hSTC- 2) is expressed in almost all tissues and regulates various biological processes. The aim of this work was to study the action of hSTC-1 and hSTC-2 in the lipid and glucose metabolism of epididymal white adipose tissue (eWAT) in rats in different nutritional states. This study shows for the first time an opposite effect of hSTC-1 and hSTC-2 on glyceride-glycerol generation from glucose in eWAT of fed rats. hSTC-1 stimulated the storage of triacylglycerol in eWAT in the postprandial period, increasing glucose uptake and glyceride-glycerol generation from [sup.14]C-glucose. hSTC-2 decreased triacylglycerol synthesis, reducing glyceride-glycerol generation from [sup.14]C-glucose, direct phosphorylation of glycerol, and fatty acid synthesis from [sup.14]C-glucose in eWAT of fed rats. However, both hormones increased glucose uptake in fed and fasting states. These findings provide evidence for a direct role of hSTC-1 and hSTC-2 in the regulation of lipid and glucose metabolism in eWAT of rats. Key words: stanniocalcin 1, stanniocalcin 2, white adipose tissue, metabolism, fed, fasting, glucose, glycerol. La stanniocalcine 1 et la stanniocalcine 2 appartiennent a une famille de molecules qui presentent des effets tant paracrines qu'autocrines dans les cellules de mammiferes. La stanniocalcine 1 humaine (hSTC-1) s'exprime dans une grande variete de tissus, y compris le tissu adipeux blanc. Chez les rats alimentes, la hSTC-1 entraine une augmentation du flux carbonique du glucose aux lipides dans le tissu adipeux blanc retroperitoneal. La stanniocalcine 2 humaine (hSTC- 2) s'exprime dans presque tous les tissus et participe a la regulation de divers processus biologiques. Ces travaux avaient pour but d'etudier l'action de la hSTC-1 et de la hSTC-2 sur le metabolisme lipidique et glucidique du tissu adipeux blanc d'epididyme (TABe) chez des rats soumis a differents etats nutritionnels. Cette etude est la premiere a montrer la presence d'effets opposes de la hSTC-1 et de la hSTC-2 sur la production de glyceride-glycerol a partir du glucose dans le TABe de rats alimentes. La hSTC-1 entrainait une stimulation du stockage du triacylglycerol dans le TABe pendant la periode postprandiale, par l'augmentation de la capture de glucose et de la production de glyceride-glycerol a partir de [sup.14]C-glucose. La hSTC-2 entrainait une diminution de la synthese de triacylglycerol, par la diminution de la production de glyceride-glycerol a partir de [sup.14]C-glucose, la phosphorylation directe du glycerol et la synthese d'acide gras a partir de [sup.14]C-glucose dans le TABe de rats alimentes. Cependant, les deux hormones entrainaient une augmentation de la capture du glucose dans les etats alimentes comme de jeune. Ces resultats apportent des donnees probantes quant a un role direct de la hSTC-1 et de la hSTC-2 dans la regulation du metabolisme lipidique et glucidique dans le TABe de rat. [Traduit par la Redaction] Mots-cles : stanniocalcine 1, stanniocalcine 2, tissu adipeux blanc, metabolisme, etat alimente, jeune, glucose, glycerol., Introduction Stanniocalcin (STC) was first isolated in fish where it was shown to regulate calcium/phosphate homeostasis (Chang et al. 1995; Olsen et al. 1996). Subsequently, 2 STC isoforms (STC-1 and [...]

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant- associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS- exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes., Introduction The electronic nicotine delivery system (ENDS), or e-cigarette, entered the US market in the mid-2000s and rapidly gained popularity among tobacco smokers and never-smokers (1). Currently, an estimated 10 [...]

Osmolytes are naturally occurring molecules used by a wide variety of organisms to stabilize proteins under extreme conditions of temperature, salinity, hydrostatic pressure, denaturant concentration, and desiccation. The effects of the osmolyte trimethylamine N-oxide (TMAO) as well as the influence of detergent head group and acyl chain length on the stability of the Escherichia coli integral membrane protein glycerol facilitator (GF) tetramer to thermal and chemical denaturation by sodium dodecyl sulphate (SDS) are reported. TMAO promotes the association of the normally tetrameric a-helical protein into higher order oligomers in dodecyl-maltoside (DDM), but not in tetradecyl-maltoside (TDM), lyso-lauroylphosphatidyl choline (LLPC), or lyso-myristoylphosphatidyl choline (LMPC), as determined by dynamic light scattering (DLS); an octameric complex is particularly stable as indicated by SDS polyacrylamide gel electrophoresis. TMAO increases the heat stability of the GF tetramer an average of 10°C in the 4 detergents and also protects the protein from denaturation by SDS. However, it did not promote re-association to the tetramer when added to SDS-dissociated protein. TMAO also promotes the formation of rod-like detergent micelles, and DLS was found to be useful for monitoring the structure of the protein and the redistribution of detergent during thermal dissociation of the protein. The protein is more thermally stable in detergents with the phosphatidylcholine head group (LLPC and LMPC) than in the maltoside detergents. The implications of the results for osmolyte mechanism, membrane protein stability, and protein-protein interactions are discussed. Key words: aquaporins, detergent, glycerol facilitator, membrane protein, osmolyte, thermal stability, SDS, tetramer, TMAO. Les osmolytes sont des molecules naturelles utilisees par un large spectre d'organismes afin de stabiliser les proteines soumises a des conditions extremes de temperature, de salinite, de pression hydrostatique, de concentration d'agents denaturants et de dessiccation. Les auteurs rapportent les effets de l'oxyde de trimethylamine (TMAO), un osmolyte, de meme que l'influence de la tete polaire et de la longueur de la chaine acyle de differents detergents, sur la stabilite du tetramere du facilitateur du glycerol (GF) d'E. coli, une proteine membranaire, face a une denaturation thermique et chimique par le dodecylsulfate de sodium (SDS). Le TMAO favorise l'association de la proteine normalement a-helicoidale tetramerique en oligomeres d'ordre superieur dans le dodecyl maltoside (DDM), contrairement au tetradecyl-maltoside (TDM), a la lyso-lauroylphosphatidyl choline (LLPC) ou la lyso-myristoylphosphatidyl choline (LMPC), tel que determine par diffusion dynamique de la lumiere (DDL); le complexe octamerique est particulierement stable comme le montre l'electrophorese en gel de polyacrylamide SDS. Le TMAO augmente la stabilite thermique du tetramere de GF de 10°C en moyenne dans les quatre detergents et protege aussi la proteine de la denaturation par le SDS. Cependant, il ne favorise pas la reassociation du tetramere si on l'ajoute a la proteine dissociee par le SDS. Le TMAO favorise aussi la formation de micelles detergentes en batonnet, et le DLS s'est avere utile pour suivre la structure de la proteine et la redistribution du detergent durant la denaturation thermique de la proteine. La proteine est plus stable thermiquement dans les detergents possedant une tete polaire constituee de phosphatidylcholine (LLPC et LMPC) que dans les detergents comprenant un maltoside. Les implications de ces resultats dans les mecanismes osmolytes, la stabilite des proteines membranaires et les interactions proteine-proteine sont discutes. [Traduit par la Redaction] Mots-cles: aquaporines, detergent, facilitateur de glycerol, proteine membranaire, osmolyte, stabilite thermique, SDS, tetramere, TMAO., Introduction Many organisms use small organic osmolytes to combat dehydration (Tunnacliffe and Lapinski 2003), heat (Singer and Lindquist 1998), cold (Storey and Storey 1996), high hydrostatic pressure (Siebenaller and Somero [...]