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https://www.readbyqxmd.com/read/28938469/taming-the-flames-targeting-white-adipose-tissue-browning-in-hypermetabolic-conditions
#1
Abdikarim Abdullahi, Marc G Jeschke
In this era of increased obesity and diabetes prevalence, the browning of white adipose tissue (WAT) has emerged as a promising therapeutic target to induce weight loss and improve insulin sensitivity in this population. The browning process entails a shift in the WAT from primarily storing excess energy to the dissipation of energy as heat. However, this idealistic view of WAT browning being the saviour of the metabolic syndrome has been criticized by studies in burns and cancer patients that have shown browning to be detrimental rather than being beneficial...
August 30, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/28938455/bile-acid-alterations-are-associated-with-insulin-resistance-but-not-with-nash-in-obese-subjects
#2
Vanessa Legry, Sven Francque, Joel T Haas, An Verrijken, Sandrine Caron, Oscar Chávez-Talavera, Emmanuelle Vallez, Luisa Vonghia, Eveline Dirinck, Ann Verhaegen, Mostafa Kouach, Sophie Lestavel, Philippe Lefebvre, Luc Van Gaal, Anne Tailleux, Réjane Paumelle, Bart Staels
Context: Bile acids (BA) are signalling molecules controlling energy homeostasis which can be both toxic and protective for the liver. BA alterations have been reported in obesity, insulin resistance (IR) and non-alcoholic steatohepatitis (NASH). However whether BA alterations contribute to NASH independently of the metabolic status is unclear. Objective: To assess BA alterations associated with NASH independently of BMI and IR. Design & Setting: Patients visiting the obesity clinic of the Antwerp University Hospital (a tertiary referral facility) were recruited from 2006 to 2014...
August 4, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938444/lack-of-lrp5-signaling-in-osteoblasts-sensitizes-male-mice-to-diet-induced-disturbances-in-glucose-metabolism
#3
Soohyun P Kim, Julie L Frey, Zhu Li, Brian C Goh, Ryan C Riddle
Wnt signaling through the Lrp5 co-receptor regulates osteoblast maturation, matrix mineralization, and intermediary metabolism. In the mature osteoblast, signals downstream of Lrp5 are required for normal long-chain fatty acid β-oxidation and mice rendered deficient for this co-receptor in osteoblasts and osteocytes accumulate body fat with elevated serum lipid levels, but retain normal insulin sensitivity. In this study, we challenged Lrp5 mutant mice with a high fat diet to determine if they are more susceptible to diet-induced disturbances in glucose homeostasis...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938426/a-sustained-activation-of-pancreatic-nmdars-is-a-novel-factor-of-%C3%AE-cell-apoptosis-and-dysfunction
#4
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Yan-Hong Huang, Qing-Mei Cheng, Xiao-Hong Li, Cai-Xia Hao, Ling-Zhi Wang, Jian-Ping Xu, Ming Ji, Chen Chen, Dan-Dan Feng, Zi-Qiang Luo
Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells...
September 4, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938423/igfbp4-is-required-for-adipogenesis-and-influences-the-distribution-of-adipose-depots
#5
David E Maridas, Victoria E DeMambro, Phuong T Le, Subburaman Mohan, Clifford J Rosen
Insulin-like Growth Factor I (IGF-I) induces adipogenesis in vitro. IGF Binding Protein 4 (IGFBP4) is highly expressed in adipocytes and osteoblasts and is inhibitory of IGFs in vitro. We previously reported that Igfbp4 null mice (Igfbp4-/-) had decreased fat proportions at 8 and 16 weeks of age. However, the mechanism leading to the reduced adiposity remains unknown. The purpose of this study was to elucidate how IGFBP4 mediates adipose tissue development in vivo. Our results showed that inguinal (iWAT) and gonadal (gWAT) white adipose tissues from Igfbp4-/- mice had decreased weights and Pparγ expression...
July 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938414/sex-and-tissue-specific-role-of-estrogen-sulfotransferase-in-energy-homeostasis-and-insulin-sensitivity
#6
Wojciech G Garbacz, Mengxi Jiang, Meishu Xu, Jun Yamauchi, H Henry Dong, Wen Xie
Estrogen Sulfotransferase (EST) catalyzes the sulfoconjugation and deactivation of estrogens. Previously we showed that loss of Est in male ob/ob mice, but not in female ob/ob mice, exacerbated the diabetic phenotype, but the underlying mechanism was unclear. Here we show that transgenic reconstitution of Est in the adipose tissue, but not in the liver, attenuated diabetic phenotype in Est deficient ob/ob mice (obe). Mechanistically, adipose reconstitution of Est in obe mice (oae) resulted in reduced local and systemic inflammation, improved insulin sensitivity, and increased energy expenditure...
September 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938412/renal-metabolic-programming-is-linked-to-the-dynamic-regulation-of-a-leptin-klf15-axis-and-akt-ampk%C3%AE-signaling-in-male-offspring-of-obese-dams
#7
Philipp Kasper, Christina Vohlen, Katharina Dinger, Jasmine Mohr, Eva Hucklenbruch-Rother, Ruth Janoschek, Jessica Köth, Jan Matthes, Sarah Appel, Jörg Dötsch, Miguel A Alejandre Alcazar
Childhood obesity is associated with renal diseases. Maternal obesity is a risk factor linked to increased adipocytokines and metabolic disorders in the offspring. We therefore studied the impact of maternal obesity on renal-intrinsic insulin and adipocytokine signaling and on renal function and structure. To induce maternal obesity female mice were fed with high-fat diet (HFD) or standard diet (SD, Co) prior to mating, during gestation and throughout lactation. A third group of dams was fed HFD only during lactation (HFD-Lac)...
July 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28935866/mulberry-leaf-alleviates-streptozotocin-induced-diabetic-rats-by-attenuating-nefa-signaling-and-modulating-intestinal-microflora
#8
Yao Sheng, Shujuan Zheng, Tianshi Ma, Chuanhai Zhang, Xiaoqun Ou, Xiaoyun He, Wentao Xu, Kunlun Huang
Improvement of hyperglycemia through dietotherapy/herbal remedy is an effective approach to treating diabetes. In this study, mulberry leaf, famous for silkworm's special food and therapeutic value without any side effects, alleviated diabetes by attenuating NEFA signaling and modulating intestinal microflora. Mulberry leaf treatment significantly reduce fasting blood-glucose and HbA1c, ameliorate the blood lipid profile and improve insulin resistance in streptozotocin-induced diabetic rats. Mechanistically, we found that mulberry leaf inhibited NEFA signaling by reducing downstream signaling in the NEFA pathway, further verified by reduced PKC and improved cellular energy homeostasis based on restored expression of PGC-1α, AK2, OXPHOS and adiponectin...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935478/development-and-validation-of-a-cell-based-assay-for-the-detection-of-neutralizing-antibodies-against-recombinant-insulins
#9
Sanjukta Chatterjee, Laxmikant Vashishta, Vinit S Waichale, Vivek G Nayak, Ramakrishnan Melarkode, Charles M Donnelly, Patrick T Vallano, Narendra Chirmule, Nilanjan Sengupta
Recombinant biopharmaceuticals can induce generation of anti-drug antibodies, which could potentially neutralize therapeutic drug activity. In this report, we describe development and validation of a cell-based assay for detection of neutralizing antibodies (Nab) against insulin and insulin analogues. In order to achieve clinically meaningful sensitivity the method used an early signalling event, insulin induced insulin receptor phosphorylation as the endpoint. Percentage insulin receptor phosphorylation in cell lysates was measured using ECL based ELISA...
September 18, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28934926/irs-1-py612-and-akt-1-pkb-pt308-phosphorylation-and-antiinflammatory-effect-of-diindolylmethane-in-adipocytes-cocultured-with-macrophages
#10
Lopez-Vazquez Alfonso, Garcia B J Javier, Gonzalez G A Sofía, Urzua L P Ernesto, Del T A Susana, Bueno T M Ruth, Sanchez E Sergio, Munoz V J Francisco, Jave S L Felipe, Armendariz B J Socorro, Bastidas R B Estela
BACKGROUND: 3,3'-Diindolylmethane (DIM) is a condensation product of indole-3-carbinol, a glucosinolate naturally occurring in Brassica genus vegetables. The antiinflammatory properties of DIM through the inhibition of NF-κB, as well as its ameliorating effects on glucose tolerance and hyperglicemic states, have been described. A subclinical proinflammatory profile resultant from the interaction of adipocytes and macrophages have been reported in obesity, affecting the insulin signaling pathway, contributing to insulin resistance...
September 21, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28934747/untangling-longevity-dauer-and-healthspan-in-caenorhabditis-elegans-insulin-igf-1-signalling
#11
Collin Yvès Ewald, Jorge Iván Castillo-Quan, T Keith Blackwell
The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C...
September 22, 2017: Gerontology
https://www.readbyqxmd.com/read/28934640/continuous-longitudinal-infusion-of-rhigf-1-rhigfbp-3-in-extremely-preterm-infants-evaluation-of-feasibility-in-a-phase-ii-study
#12
Ingrid Hansen-Pupp, Ann Hellström, Mohamed Hamdani, Adina Tocoian, Nerissa C Kreher, David Ley, Boubou Hallberg
OBJECTIVE: To evaluate the feasibility of continuous longitudinal intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) for prevention of retinopathy of prematurity and other complications in extremely preterm infants (<28weeks' gestational age), based on initial sections of a phase II randomized controlled trial. DESIGN: The phase II trial was designed in four sections (A-D); we report pharmacokinetic and adverse events (AEs) data pooled for Sections B and C...
August 31, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28934637/igf-system-targeted-therapy-therapeutic-opportunities-for-ovarian-cancer
#13
REVIEW
J A L Liefers-Visser, R A M Meijering, A K L Reyners, A G J van der Zee, S de Jong
The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models...
September 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28934392/nceh-1-modulates-cholesterol-metabolism-and-protects-against-%C3%AE-synuclein-toxicity-in-a-c-elegans-model-of-parkinson-s-disease
#14
Siyuan Zhang, Samantha A Glukhova, Kim A Caldwell, Guy A Caldwell
Parkinson's disease (PD) is an aging-associated neurodegenerative disease affecting millions worldwide. Misfolding, oligomerization and accumulation of the human α-synuclein protein is a key pathological hallmark of PD and is associated with the progressive loss of dopaminergic neurons over the course of aging. Lifespan extension via the suppression of IGF-1/insulin-like signaling (IIS) offers a possibility to retard disease onset through induction of metabolic changes that provide neuroprotection. The nceh-1 gene of Caenorhabditis elegans encodes an ortholog of neutral cholesterol ester hydrolase 1 (NCEH-1), an IIS downstream protein that was identified in a screen as a modulator of α-synuclein accumulation in vivo...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28933969/psychopharmacological-advances-in-eating-disorders
#15
Hubertus Himmerich, Janet Treasure
Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) are the primary eating disorders (EDs). The only psychopharmacological treatment options for EDs with approval in some countries include fluoxetine for BN and lisdexamfetamine for BED. Given the high comorbidity and genetic correlations with other psychiatric disorders, it seems possible that novel medications for these conditions might also be effective in EDs. Areas Covered: The current scientific literature has increased our understanding of how medication could be beneficial for patients with EDs on a molecular, functional and behavioral level...
September 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28933767/hemin-improves-insulin-sensitivity-and-lipid-metabolism-in-cultured-hepatocytes-and-mice-fed-a-high-fat-diet
#16
Yi Luan, Fang Zhang, Yalan Cheng, Jun Liu, Rui Huang, Menghong Yan, Yuangao Wang, Zhishui He, Hejin Lai, Hui Wang, Hao Ying, Feifan Guo, Qiwei Zhai
Hemin is a breakdown product of hemoglobin. It has been reported that the injection of hemin improves lipid metabolism and insulin sensitivity in various genetic models. However, the effect of hemin supplementation in food on lipid metabolism and insulin sensitivity is still unclear, and whether hemin directly affects cellular insulin sensitivity is yet to be elucidated. Here we show that hemin enhances insulin-induced phosphorylation of insulin receptors, Akt, Gsk3β, FoxO1 and cytoplasmic translocation of FoxO1 in cultured primary hepatocytes under insulin-resistant conditions...
July 26, 2017: Nutrients
https://www.readbyqxmd.com/read/28933230/inhibition-of-protein-tyrosine-phosphatase-ptp1b-and-%C3%AE-glucosidase-by-geranylated-flavonoids-from-paulownia-tomentosa
#17
Yeong Hun Song, Zia Uddin, Young Min Jin, Zuopeng Li, Marcus John Curtis-Long, Kwang Dong Kim, Jung Keun Cho, Ki Hun Park
Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1-8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1-5) and dihydroflavonols (6-8)...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28933061/neuroendocrinology-of-adipose-tissue-and-gut-brain-axis
#18
Paulo Matafome, Hans Eickhoff, Liliana Letra, Raquel Seiça
Food intake and energy expenditure are closely regulated by several mechanisms which involve peripheral organs and nervous system, in order to maintain energy homeostasis.Short-term and long-term signals express the size and composition of ingested nutrients and the amount of body fat, respectively. Ingested nutrients trigger mechanical forces and gastrointestinal peptide secretion which provide signals to the brain through neuronal and endocrine pathways. Pancreatic hormones also play a role in energy balance exerting a short-acting control regulating the start, end, and composition of a meal...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28933050/toll-like-receptor-4-signaling-mediates-inflammation-and-tissue-injury-in-diabetic-nephropathy
#19
REVIEW
Giacomo Garibotto, Annalisa Carta, Daniela Picciotto, Francesca Viazzi, Daniela Verzola
Toll-like receptors (TLRs) are a class of receptors of the innate immune system which detect pathogen-associated and danger-associated molecular patterns in order to initiate an inflammatory response. TLR2 and TLR4 downward signaling causes the production of proinflammatory cytokines that can induce insulin resistance and cardiovascular damage in obesity and type 2 diabetes mellitus. In diabetic nephropathy, TLR4, nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and NLRP3 inflammasome are involved in the production and persistence of inflammation...
September 20, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28932254/branched-chain-amino-acid-supplementation-restores-reduced-insulinotropic-activity-of-a-low-protein-diet-through-the-vagus-nerve-in-rats
#20
Mami Horiuchi, Tomoya Takeda, Hiroyuki Takanashi, Yori Ozaki-Masuzawa, Yusuke Taguchi, Yuka Toyoshima, Lila Otani, Hisanori Kato, Meri Sone-Yonezawa, Fumihiko Hakuno, Shin-Ichiro Takahashi, Asako Takenaka
BACKGROUND: Previously, we reported that a low-protein diet significantly reduced insulin secretion in response to feeding within 1 h in rats, suggesting that the insulinotropic effect of dietary protein plays an important role in maintaining normal insulin release. The current study aimed to elucidate whether deficiency of certain amino acids could diminish the insulinotropic activity and to investigate whether reduced insulin secretion in response to a low-protein diet is restored by supplementation with certain amino acids...
2017: Nutrition & Metabolism
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