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https://www.readbyqxmd.com/read/29334664/methyl-dehydroabietate-counters-high-fat-diet-induced-insulin-resistance-and-hepatic-steatosis-by-modulating-peroxisome-proliferator-activated-receptor-signaling-in-mice
#1
Hiroki Yoshioka, Yuki Mizuno, Tomohiro Yamaguchi, Yoshimi Ichimaru, Koichi Takeya, Yukio Hitotsuyanagi, Tsunemasa Nonogaki, Yutaka Aoyagi
The aim of this study was to investigate the therapeutic effects of methyl dehydroabietate (mDA) on adipocyte differentiation in 3T3-L1 preadipocytes and obesity characteristics induced by high-fat diet (HFD) in mice. Adipocyte differentiation in 3T3-L1 cells was evaluated after 14 days of incubation with mDA. mDA enhanced adipocyte differentiation in 3T3-L1 cells. For the in vivo evaluation, five-week-old male C57BL/6J mice were fed HFD or normal CE-2 diet (control) for eight weeks. During the experimental period, mice were administered mDA (50 mg/kg, p...
January 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29331057/manifestations-and-mechanisms-of-myocardial-lipotoxicity-in-obesity
#2
Arthur C Sletten, Linda R Peterson, Jean E Schaffer
Environmental and socioeconomic changes over the past thirty years have contributed to a dramatic rise in the worldwide prevalence of obesity. Heart disease is among the most serious health risks of obesity, with increases in both atherosclerotic coronary heart disease and heart failure among obese individuals. In this review, we focus on primary myocardial alterations in obesity that include hypertrophic remodeling and diastolic dysfunction. Obesity-associated perturbations in myocardial and systemic lipid metabolism are important contributors to cardiovascular complications of obesity...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#3
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330372/non-estrogenic-xanthohumol-derivatives-mitigate-insulin-resistance-and-cognitive-impairment-in-high-fat-diet-induced-obese-mice
#4
Cristobal L Miranda, Lance A Johnson, Oriane de Montgolfier, Valerie D Elias, Lea S Ullrich, Joshua J Hay, Ines L Paraiso, Jaewoo Choi, Ralph L Reed, Johana S Revel, Chrissa Kioussi, Gerd Bobe, Urszula T Iwaniec, Russell T Turner, Benita S Katzenellenbogen, John A Katzenellenbogen, Paul R Blakemore, Adrian F Gombart, Claudia S Maier, Jacob Raber, Jan F Stevens
Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323138/whole-mount-adult-ear-skin-imaging-reveals-defective-neuro-vascular-branching-morphogenesis-in-obese-and-type-2-diabetic-mouse-models
#5
Tomoko Yamazaki, Wenling Li, Ling Yang, Ping Li, Haiming Cao, Sei-Ichiro Motegi, Mark C Udey, Elise Bernhard, Takahisa Nakamura, Yoh-Suke Mukouyama
Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321684/leptin-and-the-maintenance-of-elevated-body-weight
#6
REVIEW
Warren W Pan, Martin G Myers
Obesity represents the single most important risk factor for early disability and death in developed societies, and the incidence of obesity remains at staggering levels. CNS systems that modulate energy intake and expenditure in response to changes in body energy stores serve to maintain constant body adiposity; the adipocyte-derived hormone leptin and its receptor (LEPR) represent crucial regulators of these systems. As in the case of insulin resistance, a variety of mechanisms (including feedback inhibition, inflammation, gliosis and endoplasmic reticulum stress) have been proposed to interfere with leptin action and impede the systems that control body energy homeostasis to promote or maintain obesity, although the relative importance and contribution of each of these remain unclear...
January 11, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29312618/estrogen-receptor-signaling-mediates-leptin-induced-growth-of-breast-cancer-cells-via-autophagy-induction
#7
Pawan Kumar Raut, Dong Young Choi, Sang Hyun Kim, Jin Tae Hong, Taeg Kyu Kwon, Jee Heon Jeong, Pil-Hoon Park
Leptin, a hormone derived from adipose tissue, promotes growth of cancer cells via multiple mechanisms. Estrogen receptor signaling is also known to stimulate the growth of breast cancer cells. However, the involvement of estrogen receptor signaling in the oncogenic actions of leptin and its underlying mechanisms are not clearly understood. Herein, we investigated mechanisms for estrogen receptor signaling-mediated growth of breast cancer cells, particularly focusing on autophagy, which plays a crucial role in leptin-induced tumor growth...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312594/investigation-of-tcf7l2-lep-and-lepr-polymorphisms-with-esophageal-squamous-cell-carcinomas
#8
Hao Qiu, Xunting Lin, Weifeng Tang, Chao Liu, Yu Chen, Hao Ding, Mingqiang Kang, Shuchen Chen
Single nucleotide polymorphisms (SNPs) in energy metabolism related gene may be key agents in the development of human malignancies. In this study, we aimed to examine the association of transcription factor 7-like 2, Leptin (LEP) and LEP receptor (LEPR) polymorphisms with esophageal squamous cell carcinoma (ESCC). A total of 507 ESCC cases and 1,496 controls were enrolled. We found that LEPR rs6588147 AA genotype was associated with ESCC risk (AA vs. GG/GA: adjusted OR=1.90, 95%CI=1.00-3.61, P=0.049). In the stratified analyses, LEPR rs6588147 G>A polymorphism increased the risk of ESCC (<63 years subgroup: AA vs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312569/metformin-improves-nonalcoholic-fatty-liver-disease-in-obese-mice-via-down-regulation-of-apolipoprotein-a5-as-part-of-the-ampk-lxr%C3%AE-signaling-pathway
#9
Min-Jie Lin, Wen Dai, Melanie J Scott, Rong Li, Yi-Qi Zhang, Yang Yang, Lu-Zhu Chen, Xian-Sheng Huang
Apolipoprotein A5 (apoA5) has been implicated in the formation of hepatocyte lipid droplets, a histological hallmark of non-alcoholic fatty liver disease (NAFLD). Recent evidence demonstrated that liver X receptor α (LXRα), a transcription factor involved in down-regulation of APOA5 mRNA, is activated by AMP-activated protein kinase (AMPK) that contributes to metformin-related antihyperglycemic effects. In this study we investigated the role of apoA5 and AMPK/LXRα signaling pathway in metformin-related improvement of NAFLD...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311635/subcellular-localization-of-mc4r-with-adcy3-at-neuronal-primary-cilia-underlies-a-common-pathway-for-genetic-predisposition-to-obesity
#10
Jacqueline E Siljee, Yi Wang, Adelaide A Bernard, Baran A Ersoy, Sumei Zhang, Aaron Marley, Mark Von Zastrow, Jeremy F Reiter, Christian Vaisse
Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans 1-3 . Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity 4,5 . ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 ...
January 8, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29301582/association-of-polymorphisms-in-lepr-with-type-2-diabetes-and-related-metabolic-traits-in-a-chinese-population
#11
Lulu Zhang, Yingfen Qin, Danyan Liang, Li Li, Yaojie Liang, Lulin Chen, Lei Tong, Jia Zhou, Hong Li, Haiying Zhang
BACKGROUND: Leptin acts as a mediator of inflammation and energy homeostasis by activating leptin receptor (LEPR). We conducted this study to explore the association of polymorphisms in LEPR with type 2 diabetes mellitus (T2DM) and its related metabolic traits. METHODS: We performed a case-control study to investigate the association of polymorphisms in LEPR with T2DM and related metabolic traits in a Chinese population, with a total of 922 T2DM patients and 1031 nondiabetic subjects...
January 4, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29300960/soluble-leptin-receptor-predicts-insulin-sensitivity-and-correlates-with-upregulation-of-metabolic-pathways-in-men
#12
Christine Sommer, Sindre Lee, Hanne Løvdal Gulseth, Jørgen Jensen, Christian A Drevon, Kåre Inge Birkeland
Context: Plasma soluble leptin receptor (sOb-R) seems protective of gestational and type 2 diabetes in observational studies, but the mechanisms are unknown. sOb-R is formed by ectodomain shedding of membrane-bound leptin receptors (Ob-R), but its associations with mRNA expression is scarcely explored. Objective: To explore associations between plasma levels of sOb-R and 1) insulin sensitivity; 2) mRNA pathways in adipose tissue and skeletal muscle; and 3) mRNA of candidate genes for sOb-R generation in adipose tissue and skeletal muscle...
December 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29300910/foxo1-is-required-for-most-of-the-metabolic-and-hormonal-perturbations-produced-by-hepatic-insulin-receptor-deletion-in-male-mice
#13
Alisha V Ling, Mary E Gearing, Ivana Semova, Dong-Ju Shin, Rebecca Clements, Zon W Lai, Sudha B Biddinger
Insulin coordinates the complex response to feeding, affecting numerous metabolic and hormonal pathways. FoxO1 is one of several signaling molecules downstream of insulin; FoxO1 drives gluconeogenesis and is suppressed by insulin. To determine the role of FoxO1 in mediating other actions of insulin, we studied mice with hepatic deletion of the insulin receptor, FoxO1, or both. We found that mice with deletion of the insulin receptor alone showed not only hyperglycemia, but a 40% decrease in hepatic Igf1 and delayed growth during the first two months of life, a 24-fold increase in soluble leptin receptor and a 19-fold increase in plasma leptin levels...
December 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/29298511/chrysanthemum-indicum-inhibits-adipogenesis-and-activates-the-ampk-pathway-in-high-fat-diet-induced-obese-mice
#14
Sarmila Nepali, Ji-Yun Cha, Hyeon-Hui Ki, Hoon-Yeon Lee, Young-Ho Kim, Dae-Ki Kim, Bong-Joon Song, Young-Mi Lee
Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29297146/adiponectin-leptin-and-insulin-pathway-receptors-as-endometrial-cancer-subtyping-markers
#15
Evan L Busch, Marta Crous-Bou, Jennifer Prescott, Michael J Downing, Bernard A Rosner, George L Mutter, Immaculata De Vivo
Developing a system of molecular subtyping for endometrial tumors might improve insight into disease etiology and clinical prediction of patient outcomes. High body mass index (BMI) has been implicated in development of endometrial cancer through hormonal pathways and might influence tumor expression of biomarkers involved in BMI-sensitive pathways. We evaluated whether endometrial tumor expression of 7 markers from BMI-sensitive pathways of insulin resistance could effectively characterize molecular subtypes: adiponectin receptor 1, adiponectin receptor 2, leptin receptor, insulin receptor (beta subunit), insulin receptor substrate 1, insulin-like growth factor 1 receptor, and insulin-like growth factor 2 receptor...
January 2, 2018: Hormones & Cancer
https://www.readbyqxmd.com/read/29297124/metabolic-parameters-and-functional-state-of-hypothalamic-signaling-systems-in-ay-a-mice-with-genetic-predisposition-to-obesity-and-the-effect-of-metformin
#16
K V Derkach, I O Zakharova, I V Romanova, I I Zorina, A L Mikhrina, A O Shpakov
The metabolic parameters and functional state of hypothalamic systems in mice with the Yellow mutation in the Agouti locus and with obesity of the melanocortin type and the effect of metformin (MF) treatment (9 days, 200 mg/kg/day) were studied. The MF treatment led to decreased body weight and to normalization of glucose tolerance in mice. In the hypothalamus, MF restored the decreased activity of Akt kinase, the main component of leptin pathway, and normalized the increased expression of subtype 1B serotonin receptor...
November 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29296046/the-association-of-serum-leptin-levels-with-metabolic-diseases
#17
REVIEW
Jen-Pi Tsai
Leptin is a 167-amino-acid protein released by white adipose tissue and encoded by the obese gene. It has a role as a negative regulator of appetite control through sending a satiety signal to act on receptors within the hypothalamus. At normal levels, leptin can exert its effects on weight regulation according to white fat mass, induce sodium excretion, maintain vascular tone, and repair the myocardium. Beyond these effects, elevated serum leptin levels have been implicated in the pathogenesis of metabolic syndrome, diabetes mellitus, hypertension, and multiple cardiovascular diseases...
October 2017: Ci Ji Yi Xue za Zhi, Tzu-chi Medical Journal
https://www.readbyqxmd.com/read/29289646/differential-contribution-of-pomc-and-agrp-neurons-to-the-regulation-of-regional-autonomic-nerve-activity-by-leptin
#18
Balyssa B Bell, Shannon M Harlan, Donald A Morgan, Deng-Fu Guo, Kamal Rahmouni
OBJECTIVES: The autonomic nervous system is critically involved in mediating the control by leptin of many physiological processes. Here, we examined the role of the leptin receptor (LepR) in proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in mediating the effects of leptin on regional sympathetic and parasympathetic nerve activity. METHODS: We analyzed how deletion of the LepR in POMC neurons (POMCCre/LepRfl/fl mice) or AgRP neurons (AgRPCre/LepRfl/fl mice) affects the ability of leptin to increase sympathetic and parasympathetic nerve activity...
December 18, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29285462/leptin-receptors-can-be-an-alternative-target-for-new-anti-hypertensive-drug-development
#19
Mridula Ramkumar, S K Kanthlal
No abstract text is available yet for this article.
November 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29284680/cd36-defines-primitive-chronic-myeloid-leukemia-cells-less-responsive-to-imatinib-but-vulnerable-to-antibody-based-therapeutic-targeting
#20
Niklas Landberg, Sofia von Palffy, Maria Askmyr, Henrik Lilljebjörn, Carl Sandén, Marianne Rissler, Satu Mustjoki, Henrik Hjorth-Hansen, Johan Richter, Helena Ågerstam, Marcus Järås, Thoas Fioretos
Tyrosine kinase inhibitors are highly effective for treatment of chronic myeloid leukemia, but very few patients are cured. Major drawbacks with tyrosine kinase inhibitors are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase chronic myeloid leukemia cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells...
December 28, 2017: Haematologica
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