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https://www.readbyqxmd.com/read/28932870/ablation-of-kallikrein-7-klk7-in-adipose-tissue-ameliorates-metabolic-consequences-of-high%C3%A2-fat-diet-induced-obesity-by-counteracting-adipose-tissue-inflammation-in-vivo
#1
Konstanze Zieger, Juliane Weiner, Anne Kunath, Martin Gericke, Kerstin Krause, Matthias Kern, Michael Stumvoll, Nora Klöting, Matthias Blüher, John T Heiker
Vaspin is an adipokine which improves glucose metabolism and insulin sensitivity in obesity. Kallikrein 7 (KLK7) is the first known protease target inhibited by vaspin and a potential target for the treatment of metabolic disorders. Here, we tested the hypothesis that inhibition of KLK7 in adipose tissue may beneficially affect glucose metabolism and adipose tissue function. Therefore, we have inactivated the Klk7 gene in adipose tissue using conditional gene-targeting strategies in mice. Klk7-deficient mice (ATKlk7 (-/-)) exhibited less weight gain, predominant expansion of subcutaneous adipose tissue and improved whole body insulin sensitivity under a high fat diet (HFD)...
September 20, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28931850/effect-of-caloric-restriction-on-gut-permeability-inflammation-markers-and-fecal-microbiota-in-obese-women
#2
Beate Ott, Thomas Skurk, Ljiljana Hastreiter, Ilias Lagkouvardos, Sandra Fischer, Janine Büttner, Teresa Kellerer, Thomas Clavel, Michael Rychlik, Dirk Haller, Hans Hauner
Recent findings suggest an association between obesity, loss of gut barrier function and changes in microbiota profiles. Our primary objective was to examine the effect of caloric restriction and subsequent weight reduction on gut permeability in obese women. The impact on inflammatory markers and fecal microbiota was also investigated. The 4-week very-low calorie diet (VLCD, 800 kcal/day) induced a mean weight loss of 6.9 ± 1.9 kg accompanied by a reduction in HOMA-IR (Homeostasis model assessment-insulin resistance), fasting plasma glucose and insulin, plasma leptin, and leptin gene expression in subcutaneous adipose tissue...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928277/jnk-activation-of-bim-promotes-hepatic-oxidative-stress-steatosis-and-insulin-resistance-in-obesity
#3
Sara A Litwak, Lokman Pang, Sandra Galic, Mariana Igoillo-Esteve, William J Stanley, Jean-Valery Turatsinze, Kim Loh, Helen E Thomas, Arpeeta Sharma, Eric Trepo, Christophe Moreno, Daniel J Gough, Decio L Eizirik, Judy B de Haan, Esteban N Gurzov
The BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo Here we report that fat accumulation in the liver increases JNK-dependent BIM expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liver-specific BIM knockout (BLKO) mice...
September 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28928016/cxcl14-acts-as-a-specific-carrier-of-cpg-dna-into-dendritic-cells-and-activates-toll-like-receptor-9-mediated-adaptive-immunity
#4
Kosuke Tanegashima, Rena Takahashi, Hideko Nuriya, Rina Iwase, Naoto Naruse, Kohei Tsuji, Akira Shigenaga, Akira Otaka, Takahiko Hara
CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs...
September 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28926107/fenofibrate-reverses-changes-induced-by-high-fat-diet-on-metabolism-in-mice-muscle-and-visceral-adipocytes
#5
Flávia de Toledo Frias, Karina Cunha E Rocha, Mariana de Mendonça, Gilson Massahiro Murata, Hygor Nunes Araujo, Luís Gustavo Oliveira de Sousa, Érica de Souza, Sandro Massao Hirabara, Nayara de Carvalho Leite, Everardo Magalhães Carneiro, Rui Curi, Leonardo Reis Silveira, Alice Cristina Rodrigues
The effect of fenofibrate on the metabolism of skeletal muscle and visceral white adipose tissue of diet-induced obese (DIO) mice was investigated. C57BL/6J male mice were fed either a control or high-fat diet for eight weeks. Fenofibrate (50 mg/Kg b.w., daily) was administered by oral gavage during the last two weeks of the experimental period. Insulin-stimulated glucose metabolism in soleus muscles, glucose tolerance test, insulin tolerance test, indirect calorimetry, lipolysis of visceral white adipose tissue, expression of miR-103-3p in adipose tissue and miR-1a, miR-133a/b, miR-206, let7b-5p, miR-23b-3p, miR-29-3p, miR-143-3p in soleus muscle, genes related to glucose and fatty acid metabolism in adipose tissue and soleus muscle, and proteins (phospho-AMPKα2, Pgc1α, Cpt1b), intramuscular lipid staining, and activities of fatty acid oxidation enzymes in skeletal muscle were investigated...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925409/metabolic-and-genomic-adaptations-to-winter-fattening-in-a-primate-species-the-grey-mouse-lemur-microcebus-murinus
#6
J Terrien, M Gaudubois, D Champeval, V Zaninotto, L Roger, J F Riou, F Aujard
AIM: To understand the mechanisms underlying the development of metabolic changes leading to obesity remains a major world health issue. Among such mechanisms, seasonality is quite underestimated although it corresponds to the manifestation of extreme metabolic flexibility in response to a changing environment. Nevertheless, the changes induced by such flexibility are far to be understood, especially at the level of insulin signaling, genomic stability or inflammation. METHODS: Here, we investigated the metabolic regulations displayed by a seasonal primate species, the grey mouse lemur (Microcebus murinus) that exhibits pronounced changes in body mass during the 6-month winter season: a fattening period followed by a spontaneous fat loss, without ever reaching pathological stages...
August 14, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28925406/abdominal-fat-deposits-determined-by-magnetic-resonance-imaging-in-relation-to-leptin-and-vaspin-levels-as-well-as-insulin-resistance-in-the-general-adult-population
#7
F Genske, J-P Kühn, M Pietzner, G Homuth, W Rathmann, H J Grabe, H Völzke, H Wallaschofski, N Friedrich
BACKGROUND: Various fat depots including visceral (VAT), subcutaneous adipose tissue (SAT) or liver fat content (LFC) were supposed to have different influences on various entities including adipokine levels as well as insulin resistance/sensitivity. Therefore, the aim of the study was to investigate the associations of SAT, VAT and LFC with the levels of leptin and vaspin as well as insulin resistance in a general non-diabetic population. METHODS: In total, 1825 participants of the Study of Health in Pomerania were characterized according to body fat compartments and LFC determined by magnetic resonance imaging...
August 14, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28925048/the-association-between-insulin-resistance-metabolic-variables-and-depressive-symptoms-in-mexican-american-elderly-a-population-based-study
#8
Breno S Diniz, Susan Fisher-Hoch, Joseph McCormick
OBJECTIVE: Depressive symptoms are common among older adults with obesity and diabetes. Nonetheless, the mechanisms for this association are not clear but may involve changes in the insulin cascade signaling. We aimed to investigate the association, and potential mediators, between obesity, insulin resistance, and depressive symptoms among older adults from a homogenous cohort of Mexican-Americans. METHODS: We included a total of 500 Mexican-American older adults assessed in the Cameron County Health Study...
September 18, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28921894/macrophage-area-content-and-phenotype-in-hepatic-and-adipose-tissue-in-patients-with-obesity-undergoing-roux-en-y-gastric-bypass
#9
Marianne D Kristensen, Michael T Lund, Merethe Hansen, Steen S Poulsen, Thorkil Ploug, Flemming Dela, Jørn W Helge, Clara Prats
OBJECTIVE: To investigate hepatic and adipose tissue macrophage content in subjects with obesity and the role of adipose tissue macrophages in weight loss-induced improved insulin sensitivity (IS). METHODS: A cross-sectional and a longitudinal study were combined to investigate the role of macrophages in subcutaneous (SAT) and visceral (VAT) adipose tissue and the liver in obesity-induced impaired IS and improvements with weight loss. Macrophage markers (CD68, CD163, and CD206) in SAT, VAT, and the liver from patients with obesity were investigated...
September 18, 2017: Obesity
https://www.readbyqxmd.com/read/28921841/in-a-randomized-trial-in-prostate-cancer-patients-dietary-protein-restriction-modifies-markers-of-leptin-and-insulin-signaling-in-plasma-extracellular-vesicles
#10
Erez Eitan, Valeria Tosti, Caitlin N Suire, Edda Cava, Sean Berkowitz, Beatrice Bertozzi, Sophia M Raefsky, Nicola Veronese, Ryan Spangler, Francesco Spelta, Maja Mustapic, Dimitrios Kapogiannis, Mark P Mattson, Luigi Fontana
Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions...
September 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28920922/g%C3%AE-13-ablation-reprograms-myofibers-to-oxidative-phenotype-and-enhances-whole-body-metabolism
#11
Ja Hyun Koo, Tae Hyun Kim, Shi-Young Park, Min Sung Joo, Chang Yeob Han, Cheol Soo Choi, Sang Geon Kim
Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. Here, we show that muscle-specific ablation of Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Gα13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2-mediated (Rock2-mediated) phosphorylation at Ser243...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28919422/over-expression-of-ppar%C3%AE-in-obese-mice-adipose-tissue-improves-insulin-sensitivity
#12
Haruya Takahashi, Kohei Sanada, Hiroyuki Nagai, Yongjia Li, Yumeko Aoki, Takeshi Ara, Shigeto Seno, Hideo Matsuda, Rina Yu, Teruo Kawada, Tsuyoshi Goto
Peroxisome proliferator-activated receptor α (PPARα) is important in the regulation of lipid metabolism and expressed at high levels in the liver. Although PPARα is also expressed in adipose tissue, little is known about the relationship between its activation and the regulation of glucose metabolism. In this study, we developed adipose tissue specific PPARα over-expression (OE) mice. Metabolomics and insulin tolerance tests showed that OE induces branched-chain amino acid (BCAA) profile and improvement of insulin sensitivity...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28918470/assessment-of-glucose-regulation-in-pregnancy-after-gastric-bypass-surgery
#13
Christian S Göbl, Latife Bozkurt, Andrea Tura, Michael Leutner, Laura Andrei, Lukas Fahr, Peter Husslein, Wolfgang Eppel, Alexandra Kautzky-Willer
AIMS/HYPOTHESIS: Roux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB. METHODS: Sixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery...
September 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/28917185/ghrelin-and-hypothalamic-npy-agrp-expression-in-mice-are-affected-by-chronic-early-life-stress-exposure-in-a-sex-specific-manner
#14
K Y Yam, S R Ruigrok, I Ziko, S N De Luca, P J Lucassen, S J Spencer, A Korosi
Early-life stress (ES) is a risk factor for metabolic disorders (e.g. obesity) with a notoriously higher prevalence in women compared to men. However, mechanisms underlying these effects remain elusive. The development of the hypothalamic feeding and metabolic regulatory circuits occurs mostly in the early sensitive postnatal phase in rodents and is tightly regulated by the metabolic hormones leptin and ghrelin. We have previously demonstrated that chronic ES reduces circulating leptin and alters adipose tissue metabolism early and later in life similarly in both sexes...
September 7, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28915506/maternal-diethylhexyl-phthalate-exposure-affects-adiposity-and-insulin-tolerance-in-offspring-in-a-pcna-dependent-manner
#15
Brian G Hunt, Yuan-Liang Wang, Min-Shan Chen, Shao-Chun Wang, Susan E Waltz
The ubiquitous plasticizer, diethylhexyl phthalate (DEHP), is a known endocrine disruptor. However, DEHP exposure effects are not well understood. Changes in industrial and agricultural practices have resulted in increased prevalence of DEHP exposure and has coincided with the heightened occurrence of metabolic syndrome and obesity. DEHP and its metabolites are detected in the umbilical cord blood of newborns; however, the prenatal and perinatal effects of DEHP exposure have not been intensively studied. Previously, we discovered that phosphorylation (p) of proliferating cell nuclear antigen (PCNA) at tyrosine 114 (Y114) is required for adipogenesis and diet-induced obesity in mice...
September 12, 2017: Environmental Research
https://www.readbyqxmd.com/read/28914811/leptolide-improves-insulin-resistance-in-diet-induced-obese-mice
#16
Pablo Villa-Pérez, Mercedes Cueto, Ana R Díaz-Marrero, Carmen D Lobatón, Alfredo Moreno, Germán Perdomo, Irene Cózar-Castellano
Type 2 diabetes (T2DM) is a complex disease linked to pancreatic beta-cell failure and insulin resistance. Current antidiabetic treatment regimens for T2DM include insulin sensitizers and insulin secretagogues. We have previously demonstrated that leptolide, a member of the furanocembranolides family, promotes pancreatic beta-cell proliferation in mice. Considering the beneficial effects of leptolide in diabetic mice, in this study, we aimed to address the capability of leptolide to improve insulin resistance associated with the pathology of obesity...
September 15, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28913977/the-effect-of-diet-or-exercise-on-ectopic-adiposity-in-children-and-adolescents-with-obesity-a-systematic-review-and-meta-analysis
#17
REVIEW
W Hens, D Vissers, D Hansen, S Peeters, J Gielen, L Van Gaal, J Taeymans
OBJECTIVE: Ectopic fat depostion in youth with obesity is associated with an increased cardiovascular disease risk. The aim of this meta-analysis was to summarize the evidence for the use of diet and/or exercise on ectopic adiposity in this population. METHODS: A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Clinical trials that assessed ectopic fat deposition and included study arms with diet and/or exercise were searched in PubMed, PEDro and the Cochrane database...
September 14, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28913889/prevalence-and-contributors-to-low-grade-inflammation-in-three-u-s-populations-of-reproductive-age-women
#18
Lindsey A Sjaarda, Rose G Radin, Chandra Swanson, Daniel L Kuhr, Sunni L Mumford, Noya Galai, Robert M Silver, Jean Wactawski-Wende, Neil J Perkins, Enrique F Schisterman
BACKGROUND: Inflammation, measured by high-sensitivity C-reactive protein (hsCRP), is linked to adverse reproductive outcomes. However, prevalence and predictors of low-grade inflammation are poorly understood among reproductive age women. Therefore, the current aim was to characterize: (i) the prevalence of elevated hsCRP and (ii) whether the association of various demographic, anthropometric, life style, and metabolic characteristics with higher hsCRP varies across populations of reproductive age women with varying risk profiles for adverse reproductive outcomes...
September 15, 2017: Paediatric and Perinatal Epidemiology
https://www.readbyqxmd.com/read/28913658/liver-specific-reconstitution-of-ceacam1-reverses-the-metabolic-abnormalities-caused-by-its-global-deletion-in-male-mice
#19
Lucia Russo, Harrison T Muturi, Hilda E Ghadieh, Simona S Ghanem, Thomas A Bowman, Hye Lim Noh, Sezin Dagdeviren, Godwin Y Dogbey, Jason K Kim, Garrett Heinrich, Sonia M Najjar
AIMS/HYPOTHESIS: The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes insulin clearance. Mice with global null mutation (Cc1 (-/-)) or with liver-specific inactivation (L-SACC1) of Cc1 (also known as Ceacam1) gene display hyperinsulinaemia resulting from impaired insulin clearance, insulin resistance, steatohepatitis and obesity. Because increased lipolysis contributes to the metabolic phenotype caused by transgenic inactivation of CEACAM1 in the liver, we aimed to further investigate the primary role of hepatic CEACAM1-dependent insulin clearance in insulin and lipid homeostasis...
September 14, 2017: Diabetologia
https://www.readbyqxmd.com/read/28912810/latent-inflammation-and-insulin-resistance-in-adipose-tissue
#20
REVIEW
I S Stafeev, A V Vorotnikov, E I Ratner, M Y Menshikov, Ye V Parfyonova
Obesity is a growing problem in modern society and medicine. It closely associates with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hepatic and cardiovascular diseases such as nonalcoholic fatty liver disease, atherosclerosis, myocarditis, and hypertension. Obesity is often associated with latent inflammation; however, the link between inflammation, obesity, T2DM, and cardiovascular diseases is still poorly understood. Insulin resistance is the earliest feature of metabolic disorders. It mostly develops as a result of dysregulated insulin signaling in insulin-sensitive cells, as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare...
2017: International Journal of Endocrinology
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