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https://www.readbyqxmd.com/read/29150432/the-ikk-related-kinase-tbk1-activates-mtorc1-directly-in-response-to-growth-factors-and-innate-immune-agonists
#1
Cagri Bodur, Dubek Kazyken, Kezhen Huang, Bilgen Ekim Ustunel, Kate A Siroky, Aaron Seth Tooley, Ian E Gonzalez, Daniel H Foley, Hugo A Acosta-Jaquez, Tammy M Barnes, Gabrielle K Steinl, Kae-Won Cho, Carey N Lumeng, Steven M Riddle, Martin G Myers, Diane C Fingar
The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150385/igf-1r-mrna-expression-is-increased-in-obese-children
#2
Rafaela Cristina Ricco, Rubens Garcia Ricco, Mariangela Carletti Queluz, Mariana Teresa Sarti de Paula, Patricia Volpon Atique, Rodrigo José Custódio, Hugo Tourinho Filho, Raphael Del Roio Liberatori, Carlos Eduardo Martinelli
OBJECTIVES: Obese children are often taller than age-matched subjects. Reports on GH and IGF-I levels in obese individuals are controversial, with normal and reduced GH-IGF-I levels having been reported in this group of patients. Thus, the aim of this study was to analyse insulin-like growth factor type 1 receptor (IGF-IR) mRNA expression in obese children. METHODS: Forty-seven pre-pubertal children were included in this study: 29 were obese and taller than their target height, and 18 were normal eutrophic controls...
November 11, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29149730/divergence-of-insulin-superfamily-ligands-receptors-and-igf-binding-proteins-in-marine-versus-freshwater-stickleback-evidence-of-selection-in-known-and-novel-genes
#3
Tim Pellissier, Hend Al Nafea, Sara V Good
Three-spine stickleback (Gasterosteus aculeatus) is a teleost model for understanding genetic, physiological and morphological changes accompanying freshwater (FW) adaptation. There is growing evidence that the insulin superfamily plays important roles in traits involved in marine and FW adaptation. We performed a candidate gene analysis to look for evidence of selection on 33 insulin superfamily ligand-receptor genes and insulin-like growth factor binding proteins (Igfbp's) in stickleback. Using genotype data from 11 marine and 10 FW populations, we calculated the number of SNPs per site in regulatory and intronic regions, the number of synonymous and nonsynonymous mutations in coding regions, Wright's fixation index (Fst), and performed t-tests to identify SNPs with divergent genotype frequencies between marine/FW versus Atlantic/Pacific populations...
November 10, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/29149676/high-salt-diet-decreases-reproductive-performance-in-rams-and-down-regulates-gene-expression-of-some-components-of-the-renin-angiotensin-system-in-the-testis
#4
Yi Fang, Rongzhen Zhong, Xuezhao Sun, Daowei Zhou
Although salt-tolerant plants can be used to combat dryland salinity, these plants contain high concentrations of salt (NaCl), which may have deleterious effects if fed to livestock. Twenty-four Merino rams (9 mo of age) with similar body weight were equally allocated to two groups and fed a normal- or high-salt diet (0.5 and 12% NaCl, respectively) for 3 mo. Rams fed the high-salt diet had lower live weight gains, higher water intake, smaller testes (466 ± 48.4 vs 604 ± 51.1 g) and reductions (P <0...
November 10, 2017: Theriogenology
https://www.readbyqxmd.com/read/29149028/changes-of-cerebral-and-or-peripheral-adenosine-a%C3%A2-receptor-and-igf-i-concentrations-under-extended-sleep-duration-in-rats
#5
Mounir Chennaoui, Pierrick J Arnal, Rodolphe Dorey, Fabien Sauvet, Sylvain Ciret, Thierry Gallopin, Damien Leger, Catherine Drogou, Danielle Gomez-Merino
Extended sleep improves sustained attention and reduces sleep pressure in humans. Downregulation of adenosine A₁ receptor (A₁R) and modulation of the neurotrophic factor insulin growth factor-1 (IGF-I) in brain structures controlling attentional capacities could be involved. In the frontal cortex and hippocampus of rats, we measured adenosine A₁R and IGF-I protein concentrations after photoperiod-induced sleep extension. Two groups of twelve rats were adapted over 14 days to a habitual (CON) 12:12 light-dark (LD) schedule and an extended (EXT) 16:8 LD schedule...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29148123/donohue-syndrome-a-review-of-literature-case-series-and-anesthetic-considerations
#6
REVIEW
Alana Kirkwood, Grant Stuart, Louise Harding
BACKGROUND: Donohue syndrome is a rare autosomal recessive disorder of insulin resistance, causing a functional defect in insulin receptor function, and affecting the ability of the insulin to bind the receptor. Features include severe hyperinsulinism and fasting hypoglycemia, along with severe failure to thrive despite feeding. An accelerated fasting state results in muscle wasting, decreased subcutaneous fat, and an excess of thick skin. A reduced thoracic diameter is accentuated by increased abdominal distension, which impacts on respiratory reserve...
November 17, 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/29146976/association-of-a-variant-in-the-gene-encoding-for-erv1-chemr23-with-reduced-inflammation-in-visceral-adipose-tissue-from-morbidly-obese-individuals
#7
Cristina López-Vicario, Bibiana Rius, José Alcaraz-Quiles, Ana González-Périz, Ana Isabel Martínez-Puchol, Mireia Casulleras, Marta Duran-Güell, Ainitze Ibarzabal, Ricard Corcelles, Andrés Laguna-Fernández, Magnus Back, Esther Titos, Joan Clària
Obesity comorbidities are closely associated with chronic low-grade adipose tissue inflammation. A number of SNPs associated with inflammation has been identified, underscoring the impact of genetic determinants on this process. Here, we screened SNPs in genes with pro-inflammatory (IL-1β, IL-6, STAT3 and JAK2), anti-inflammatory (IL-10 and SOCS3) and pro-resolving (ERV1/ChemR23) properties in 101 obese and 99 non-obese individuals. Among the SNPs analyzed, we identified that individuals carrying a C allele in the rs1878022 polymorphism of the ERV1/ChemR23 gene, which encodes for the receptor of the pro-resolving mediator RvE1, had increased ERV1/ChemR23 protein expression and reduced levels of the inflammatory cytokine IL-6 in adipose tissue...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146554/ingap-pp-effects-on-%C3%AE-cell-mass-and-function-are-related-to-its-positive-effect-on-islet-angiogenesis-and-vegfa-production
#8
Carolina Lisi Román, Bárbara Maiztegui, Héctor Del Zotto, Juan José Gagliardino, Luis Emilio Flores
Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances β-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, β-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis...
November 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29145563/neuronal-dnmt1-deficiency-attenuates-diet-induced-obesity-in-mice
#9
Emily C Bruggeman, John T Garretson, Rui Wu, Hang Shi, Bingzhong Xue
Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development, but the role of neuronal DNA methyltransferases (Dnmts; enzymes that catalyze DNA methylation) in energy balance remains poorly understood. We investigated whether neuronal Dnmt1 regulates normal energy homeostasis and obesity development using a novel Dnmt1 knockout mouse model, Dnmt1fl/fl Synapsin1Cre (ND1KO), which specifically deletes Dnmt1 in neurons.Neuronal Dnmt1 deficiency reduced adiposity in chow-fed mice and attenuated obesity in HFD-fed male mice...
November 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/29145541/variations-in-adipor1-but-not-adipor2-are-associated-with-hypertriglyceridemia-and-diabetes-in-an-admixed-latin-american-population
#10
Gustavo Gustavo Mora-García, María S Ruiz-Díaz, Fabian Espitia-Almeida, Doris Gómez-Camargo
BACKGROUND: Adiponectin is a hormone secreted by adipose tissue. It regulates glycolysis and lipolysis and is involved in the pathophysiology of diabetes and related disorders. Its activity is mainly mediated by the transmembrane receptors AdipoR1 and AdipoR2, which are encoded by ADIPOR1 (1q32.1) and ADIPOR2 (12p13.33) genes, respectively. In genetic association studies, single nucleotide polymorphisms (SNPs) in or near these genes have been associated with metabolic alterations. However, these relationships are still controversial...
July 2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/29142285/blockade-of-cb1-cannabinoid-receptor-alters-gut-microbiota-and-attenuates-inflammation-and-diet-induced-obesity
#11
Pegah Mehrpouya-Bahrami, Kumaraswamy Naidu Chitrala, Mitra S Ganewatta, Chuanbing Tang, E Angela Murphy, Reilly T Enos, Kandy T Velazquez, Jamie McCellan, Mitzi Nagarkatti, Prakash Nagarkatti
Obesity is characterized by chronic low-grade, systemic inflammation, altered gut microbiota, and gut barrier disruption. Additionally, obesity is associated with increased activity of endocannabinoid system (eCB). However, the clear connection between gut microbiota and the eCB system in the regulation of energy homeostasis and adipose tissue inflammation and metabolism, remains to be established. We investigated the effect of treatment of mice with a cannabinoid receptor 1 (CB1) antagonist on Diet-Induced Obesity (DIO), specifically whether such a treatment that blocks endocannabinoid activity can induce changes in gut microbiota and anti-inflammatory state in adipose tissue...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141508/anti-m%C3%A3-llerian-hormone-amh-may-stall-ovarian-cortex-function-through-modulation-of-hormone-receptors-other-than-the-amh-receptor
#12
Laura Detti, Nicole M Fletcher, Ghassan M Saed, Irene Peregrin-Alvarez, Rebecca A Uhlmann
OBJECTIVE: To test whether recombinant anti-Müllerian hormone (AMH) can inhibit ovarian cortex function by modulating the expression of other hormone receptors. MATERIALS AND METHODS: Pilot experimental study with ovarian cortex obtained from 5 patients. Immediately after explant, the ovarian cortex specimens were divided into 5 equal fragments. One fragment was flash-frozen (uncultured) and 4 were incubated for 48 hours at 37°C in a pH-adjusted gamete buffer medium with increasing AMH concentrations of 0, 5, 25, and 50 ng/mL...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29138984/11%C3%AE-hydroxysteroid-dehydrogenases-and-hypertension-in-the-metabolic-syndrome
#13
REVIEW
Matthew A Bailey
The metabolic syndrome describes a clustering of risk factors-visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension-that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25-30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome...
November 14, 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/29138870/insig2-rs7566605-single-nucleotide-variant-and-global-dna-methylation-index-levels-are-associated-with-weight-loss-in-a-personalized-weight-reduction-program
#14
Francesca Pirini, Sebastian Rodriguez-Torres, Bola Grace Ayandibu, María Orera-Clemente, Alberto Gonzalez-de la Vega, Fahcina Lawson, Roland J Thorpe, David Sidransky, Rafael Guerrero-Preston
Single nucleotide polymorphisms associated with lipid metabolism and energy balance are implicated in the weight loss response caused by nutritional interventions. Diet‑induced weight loss is also associated with differential global DNA methylation. DNA methylation has been proposed as a predictive biomarker for weight loss response. Personalized biomarkers for successful weight loss may inform clinical decisions when deciding between behavioral and surgical weight loss interventions. The aim of the present study was to investigate the association between global DNA methylation, genetic variants associated with energy balance and lipid metabolism, and weight loss following a non‑surgical weight loss regimen...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138637/regulation-of-osteogenic-differentiation-of-placental-derived-mesenchymal-stem-cells-by-insulin-like-growth-factors-and-low-oxygen-tension
#15
Amer Youssef, Victor K M Han
Placental mesenchymal stem cells (PMSCs) are multipotent cells that can differentiate in vitro to multiple lineages, including bone. Insulin-like growth factors (IGFs, IGF-1 and IGF-2) participate in maintaining growth, survival, and differentiation of many stem cells, including osteoprogenitors. Low oxygen tension (PO2) can maintain stem cell multipotency and impede osteogenic differentiation. In this study, we investigated whether PMSC osteogenic differentiation is influenced by low PO2 and by IGFs. Our results indicated that low PO2 decreased osteogenic markers RUNX2 and OPN; however, re-exposure to higher oxygen tension (room air) restored differentiation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29138225/androgen-signaling-expands-%C3%AE-cell-mass-in-male-rats-and-%C3%AE-cell-androgen-receptor-is-degraded-under-high-glucose-conditions
#16
Naoki Harada, Yasuhiro Yoda, Yusuke Yotsumoto, Tatsuya Masuda, Yuji Takahashi, Takahiro Katsuki, Kenji Kai, Nobuaki Shiraki, Hiroshi Inui, Ryoichi Yamaji
A deficient pancreatic β-cell mass increases the risk of type 2 diabetes mellitus. Here, we investigated the effects of testosterone on the development of pancreatic β-cell mass in male rats. The β-cell mass of male rats castrated at 6 weeks of age was reduced to ~30% of that of control rats at 16 weeks of age, and castration caused glucose intolerance. Loss of β-cell mass occurred due to decreases in islet density/pancreas and β-cell cluster size. Castration was negatively associated with the number of Ki67-positive β-cells and positively associated with the number of TUNEL-positive β-cells...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29138180/inhibition-of-vascular-c-jun-n-terminal-kinase-2-improves-obesity-induced-endothelial-dysfunction-after-roux-en-y-gastric-bypass
#17
Petia Doytcheva, Thomas Bächler, Erika Tarasco, Vincenzo Marzolla, Michael Engeli, Giovanni Pellegrini, Simona Stivala, Lucia Rohrer, Francesco Tona, Giovanni G Camici, Paul M Vanhoutte, Christian M Matter, Thomas A Lutz, Thomas F Lüscher, Elena Osto
BACKGROUND: Roux-en-Y gastric bypass (RYGB) reduces obesity-associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c-Jun N-terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity-induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. METHODS AND RESULTS: After 7 weeks of a high-fat high-cholesterol diet, obese rats underwent RYGB or sham surgery; sham-operated ad libitum-fed rats received, for 8 days, either the control peptide D-TAT or the JNK peptide inhibitor D-JNKi-1 (20 mg/kg per day subcutaneous)...
November 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29137982/adipose-tissue-complement-factor-b-promotes-adipocyte-maturation
#18
Hiroaki Matsunaga, Misaki Iwashita, Takanori Shinjo, Akiko Yamashita, Mitsudai Tsuruta, Shoichiro Nagasaka, Ataru Taniguchi, Mitsuo Fukushima, Naoya Watanabe, Fusanori Nishimura
OBJECTIVES: It is well-known that the complement system plays an essential role in host immunity. Observational studies have indicated that complement system-related molecules such as complement factor B (CfB) and other components are correlated with obesity and/or insulin resistance parameters. In this study, we investigated the role of adipocyte-derived CfB in adipose tissue metabolism. METHODS: We investigated the expression level of complement system-related genes in adipocytes...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137928/camkii%C3%AE-expression-in-a-mouse-model-of-nmdar-hypofunction-schizophrenia-putative-roles-for-igf-1r-and-tlr4
#19
O M Ogundele, C C Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice...
November 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29137280/ppar%C3%AE-sumoylation-mediated-lipid-accumulation-in-lung-cancer
#20
Ai N H Phan, Vu T A Vo, Tuyen N M Hua, Min-Kyu Kim, Se-Young Jo, Jong-Whan Choi, Hyun-Won Kim, Jaekyoung Son, Young-Ah Suh, Yangsik Jeong
Metabolic reprogramming as a crucial emerging hallmark of cancer is critical for tumor cells to maintain cellular bioenergetics, biosynthesis and reduction/oxidation (REDOX) balance. Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor regulating transcription of diverse gene sets involved in inflammation, metabolism, and suppressing tumor growth. Thiazolidinediones (TZDs), as selective PPARγ ligands, are insulin-sensitizing drugs widely prescribed for type 2 diabetic patients in the clinic...
October 10, 2017: Oncotarget
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