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https://www.readbyqxmd.com/read/28928277/jnk-activation-of-bim-promotes-hepatic-oxidative-stress-steatosis-and-insulin-resistance-in-obesity
#1
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/28927079/new-use-of-microsatellite-instability-analysis-in-endometrial-cancer
#2
Haruko Kunitomi, Kouji Banno, Megumi Yanokura, Takashi Takeda, Moito Iijima, Kanako Nakamura, Miho Iida, Masataka Adachi, Keiko Watanabe, Yusuke Matoba, Yusuke Kobayashi, Eiichiro Tominaga, Daisuke Aoki
The increasing incidence of obesity and diabetes due to changes in diet, earlier menarche, delayed menopause, late marriage, and declining birth rate have resulted in an increase in the number of endometrial cancer cases over the last few decades. Although surgical therapy is sufficient for early endometrial cancer, there is no effective therapy for patients with advanced and recurrent endometrial cancer. The oncogenic mechanism of endometrial cancer involves microsatellite instability (MSI) caused by dysfunction of DNA mismatch repair genes in 30% of patients...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28918389/glucagon-like-peptide-1-receptor-agonists-for-the-management-of-obesity-and-non-alcoholic-fatty-liver-disease-a-novel-therapeutic-option
#3
REVIEW
Gauri Dhir, Kenneth Cusi
Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM), and is associated with a cluster of metabolic factors that lead to poor cardiovascular outcomes. In non-alcoholic fatty liver disease (NAFLD), liver fat (triglyceride) accumulation closely mirrors adipose tissue dysfunction and insulin resistance in obesity and T2DM. It is now recognized as the most common chronic liver disease in Westernized societies, often progressing to more severe forms of the disease such as nonalcoholic steatohepatitis (NASH), or cirrhosis and hepatocellular carcinoma...
September 15, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/28913816/re-visiting-the-endocannabinoid-system-and-its-therapeutic-potential-in-obesity-and-associated-diseases
#4
REVIEW
Joyce M Richey, Orison Woolcott
PURPOSE OF REVIEW: The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. RECENT FINDINGS: Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects...
September 14, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28901468/apolipoprotein-a5-regulates-intracellular-triglyceride-metabolism-in-adipocytes
#5
Xiao-Yan Zheng, Bi-Lian Yu, Yu-Fei Xie, Shui-Ping Zhao, Chen-Lu Wu
It has previously been demonstrated that apolipoprotein A5 (apoA5) can be internalized by human adipocytes and significantly decreases intracellular triglyceride content. In the present study, endocytosis of apoA5 by adipocytes under different conditions, and the underlying mechanism by which apoA5 regulates cellular triglyceride storage, was investigated. The results revealed that the apoA5 protein was detected in human subcutaneous abdominal adipose tissues. In addition, the uptake of apoA5 was attenuated in human obese adipose tissues and in cultured adipocytes with hypertrophy or insulin resistance...
September 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28895785/preclinical-pharmacokinetic-characterization-of-an-adipose-tissue-targeting-monoclonal-antibody-in-obese-and-non-obese-animals
#6
Sharmila Rajan, Danielle Mandikian, Amos Baruch, Thomas R Gelzleichter, Dale Stevens, Junichiro Sonoda, Kyra Cowan, C Andrew Boswell, Eric Stefanich
Target receptor levels can influence pharmacokinetics (PK) or pharmacodynamics (PD) of monoclonal antibodies (mAbs), and can affect drug development of this class of molecules. We generated an effector-less humanized bispecific antibody that selectively activates fibroblast growth factor receptor (FGFR)1 and βKlotho receptor, a FGF21 receptor complex highly expressed in both white and brown adipocytes. The molecule shows cross-species binding with comparable equilibrium binding affinity (Kd) for human, cynomolgus monkey, and mouse FGFR1/βKlotho...
September 12, 2017: MAbs
https://www.readbyqxmd.com/read/28891325/epigenetics-and-immunometabolism-in-diabetes-and-aging
#7
Tomasz J Guzik, Francesco Cosentino
SIGNIFICANCE: A strong relationship between hyperglycemia, impaired insulin pathway and cardiovascular disease in type 2 diabetes (T2D) is linked to oxidative stress and inflammation. Immunometabolic pathways link these pathogenic processes and pose important potential therapeutic targets. Recent Advances: The link between immunity and metabolism is bi-directional and includes the role of inflammation in the pathogenesis of metabolic disorders such as T2D, obesity, metabolic syndrome and hypertension as well as the role of metabolic factors in regulation of immune cell functions...
September 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28883393/fas-cell-surface-death-receptor-controls-hepatic-lipid-metabolism-by-regulating-mitochondrial-function
#8
Flurin Item, Stephan Wueest, Vera Lemos, Sokrates Stein, Fabrizio C Lucchini, Rémy Denzler, Muriel C Fisser, Tenagne D Challa, Eija Pirinen, Youngsoo Kim, Silvio Hemmi, Erich Gulbins, Atan Gross, Lorraine A O'Reilly, Markus Stoffel, Johan Auwerx, Daniel Konrad
Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28872123/ileectomy-induced-bile-overaccumulation-in-mouse-intestine
#9
Rongli Zhang, Jonathan W Ray, Mukesh K Jain, Shuxin Han
Intestinal resection is a common therapeutic approach for human diseases such as obesity, inflammatory bowel disease, Crohn's disease, and colon cancer that often results in severe short bowel syndrome-like adverse effects including bile acid diarrhea, dehydration, electrolyte disturbances, and nutrient malabsorption. Here we introduce a murine ileal resection model, termed ileectomy, to evaluate tissue communication and the maintenance of systemic homeostasis. After ileal resection, circulating blood is permanently devoid of the ileum-specific endocrine hormone fibroblast growth factor 15 (FGF15), which releases its endocrinal inhibition of bile acid synthesis in the liver...
August 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28857469/the-nlpr3-inflammasome-and-obesity-related-kidney-disease
#10
REVIEW
Ben Ke, Wen Shen, Xiangdong Fang, Qinghua Wu
Over the past decade, the prevalence of obesity has increased, accompanied by a parallel increase in the prevalence of chronic kidney disease (CKD). Mounting evidence suggests that high body mass index (BMI) and obesity are important risk factors for CKD, but little is known about the mechanisms of obesity-related kidney disease (ORKD). The NLRP3 inflammasome is a polyprotein complex that plays a crucial role in the inflammatory process, and numerous recent studies suggest that the NLRP3 inflammasome is involved in ORKD development and may serve as a key modulator of ORKD...
August 31, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28843826/zoledronic-acid-an-fpps-inhibitor-ameliorates-liver-steatosis-through-inhibiting-hepatic-de-novo-lipogenesis
#11
Qiaoli Tang, Shan Jiang, Wenjun Jia, Di Shen, Yudong Qiu, Yue Zhao, Bin Xue, Chaojun Li
Currently, there is no standard therapy for non-alcoholic fatty liver disease (NAFLD), and statins have been developed as a first-line pharmaceutical therapeutic option for NAFLD-associated dyslipidemia. However, prolonged statins therapy has side effects, as statins inhibit HMG-CoA reductase, an enzyme at the very beginning of the mevalonate pathway. Here, we found that zoledronic acid (ZA), an inhibitor of farnesyl diphosphate synthase in the downstream mevalonate pathway, could attenuate hepatic lipid accumulation and improve liver injury in both high-fat diet-induced C57BL/6J mice and ob/ob mice...
August 24, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28829997/msx2-is-required-for-vascular-smooth-muscle-cells-osteoblastic-differentiation-but-not-calcification-in-insulin-resistant-ob-ob-mice
#12
Maria Claudina Andrade, Luciana S Carmo, Elisangela Farias-Silva, Marcel Liberman
BACKGROUND AND AIMS: Obesity and diabetes potentiate vascular calcification by increasing vascular smooth muscle cells osteoblastic differentiation mediated by the transcription factor Msx2 and bone morphogenetic protein-2 signaling. However, Bmp-2/Msx2 crosstalk to induce VSMC osteogenic phenotype transition and calcification is poorly understood in diabetes. We aimed to investigate mechanisms underlying Bmp-2-driven VSMC osteogenic differentiation and calcification in leptin-deficient ob/ob mice...
July 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28828264/exercise-training-with-dietary-restriction-enhances-circulating-irisin-level-associated-with-increasing-endothelial-progenitor-cell-number-in-obese-adults-an-intervention-study
#13
Junhao Huang, Shen Wang, Fengpeng Xu, Dan Wang, Honggang Yin, Qinhao Lai, Jingwen Liao, Xiaohui Hou, Min Hu
OBJECTIVE: Circulating endothelial progenitor cells (EPCs) correlate negatively with obesity. Previous studies have shown that exercise significantly restores circulating EPC levels in obese people; however, the underlying mechanisms have not been elucidated. Recently, irisin has been reported to have a critical role in the regulation of EPCs. This exercise-induced myokine has been demonstrated to play a therapeutic role in obesity. In this study, we hypothesized that the increase in circulating irisin may form a link with increasing EPC levels in obese people after exercise...
2017: PeerJ
https://www.readbyqxmd.com/read/28820743/sleep-apnea-a-review-of-diagnostic-sensors-algorithms-and-therapies
#14
Mehdi Shokoueinejad, Chris Fernandez, Emily Carroll, Fa Wang, Jake Levin, Sam Rusk, Nick Glattard, Ashley Mulchrone, Xuan Zhang, Ailiang Xie, Mihaela Teodorescu, Jerome Dempsey, John Webster
While public awareness of sleep related disorders is growing, sleep apnea syndrome (SAS) remains a public health and economic challenge. Over the last two decades, extensive controlled epidemiologic research has clarified the incidence, risk factors including the obesity epidemic, and global prevalence of obstructive sleep apnea (OSA), as well as establishing a growing body of literature linking OSA with cardiovascular morbidity, mortality, metabolic dysregulation, and neurocognitive impairment. The US Institute of Medicine Committee on Sleep Medicine estimates that 50-70 million US adults have sleep or wakefulness disorders...
August 18, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28818460/the-design-and-synthesis-of-a-novel-compound-of-berberine-and-baicalein-that-inhibits-the-efficacy-of-lipid-accumulation-in-3t3-l1-adipocytes
#15
Mengjiao Hao, Zhuoji Guan, Yan Li, Lixian Liu, Xiao Yuan, Ying Gao, Weimin Li
The combination of berberine and baicalein may have a better therapeutic effect against disease. To explore the combined effect of baicalein and berberine in the treatment of obesity, we designed and synthesized a hybrid compound, and its biological activities were evaluated in 3T3-L1 adipocytes. The structures of the berberine-baicalein (BBS) compounds were confirmed by (1)H NMR, (13)C NMR, ultraviolet spectroscopy and high resolution mass spectrometry (HRMS). The present study showed that the IC50 values of the inhibitory effects of baicalein, berberine and BBS against 3T3-L1 cells were 29...
August 9, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28789869/stress-induced-eating-and-the-relaxation-response-as-a-potential-antidote-a-review-and-hypothesis
#16
REVIEW
Tasmiah Masih, James A Dimmock, Elissa S Epel, Kym J Guelfi
There is an accumulating body of evidence to indicate that stress leads to the consumption of unhealthy, energy-dense, palatable food, potentially contributing to the alarming global prevalence of chronic diseases, including obesity. However, comparatively little research has been devoted to addressing how best to remedy this growing problem. We provide an overview of the influence of stress on dietary intake, and then explore the novel, yet simple, possibility that regular elicitation of the relaxation response may effectively reduce stress-induced eating via both physiological neuroendocrine and reward pathways and psychological pathways involving emotion regulation, and habitual coping...
August 5, 2017: Appetite
https://www.readbyqxmd.com/read/28781772/enriched-endoplasmic-reticulum-mitochondria-interactions-result-in-mitochondrial-dysfunction-and-apoptosis-in-oocytes-from-obese-mice
#17
Lihong Zhao, Tengfei Lu, Lei Gao, Xiangwei Fu, Shien Zhu, Yunpeng Hou
BACKGROUND: Maternal obesity alters oocytes and subsequent fetal metabolism. An increasing number of studies have shown that the endoplasmic reticulums (ER) or mitochondria have important effects on oocyte quality, but there has been no study of the effect of mitochondria-associated ER membranes (MAMs) on oocyte quality. The present study was designed to assess whether the level of MAM and MAM-related proteins were different in oocytes from obese and control mice. RESULTS: First, oocytes from mice with high-fat-diet (HFD)-induced obesity had higher levels (either greater numbers or a higher proportion for the same numbers) of MAM than oocytes from control mice...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28770317/mitochondrial-h-atp-synthase-in-human-skeletal-muscle-contribution-to-dyslipidaemia-and-insulin-resistance
#18
Laura Formentini, Alexander J Ryan, Manuel Gálvez-Santisteban, Leslie Carter, Pam Taub, John D Lapek, David J Gonzalez, Francisco Villarreal, Theodore P Ciaraldi, José M Cuezva, Robert R Henry
AIMS/HYPOTHESIS: Mitochondria are important regulators of the metabolic phenotype in type 2 diabetes. A key factor in mitochondrial physiology is the H(+)-ATP synthase. The expression and activity of its physiological inhibitor, ATPase inhibitory factor 1 (IF1), controls tissue homeostasis, metabolic reprogramming and signalling. We aimed to characterise the putative role of IF1 in mediating skeletal muscle metabolism in obesity and diabetes. METHODS: We examined the 'mitochondrial signature' of obesity and type 2 diabetes in a cohort of 100 metabolically characterised human skeletal muscle biopsy samples...
August 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/28769873/targeting-obesity-and-diabetes-to-treat-heart-failure-with-preserved-ejection-fraction
#19
REVIEW
Raffaele Altara, Mauro Giordano, Einar S Nordén, Alessandro Cataliotti, Mazen Kurdi, Saeed N Bajestani, George W Booz
Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28757640/effects-of-peripheral-administration-of-a-neuromedin-u-receptor-2-selective-agonist-on-food-intake-and-body-weight-in-obese-mice
#20
T Kaisho, H Nagai, T Asakawa, N Suzuki, H Fujita, K Matsumiya, N Nishizawa, Y Kanematsu-Yamaki, K Dote, J-I Sakamoto, T Asami, S Takekawa
BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions including regulation of smooth-muscle contraction, blood pressure, stress responses, and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system, respectively. It is reported that the NMU signaling system regulates food intake and body weight via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity...
July 31, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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