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primary adipocyte diabetes

Kotaro Sakamoto, Yayoi Kawata, Yasushi Masuda, Tadashi Umemoto, Takashi Ito, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki, Hiroshi Inooka
Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually...
October 4, 2016: Biochemical and Biophysical Research Communications
Atsushi Obata, Shinji Kamei, Seizo Okauchi, Tomohiko Kimura, Hidenori Hirukawa, Akihito Tanabe, Tomoe Kinoshita, Kenji Kohara, Fuminori Tatsumi, Masashi Shimoda, Shuhei Nakanishi, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
INTRODUCTION: It is known that chylomicronemia is caused by several pathologies and is classified as primary and secondary chylomicronemia. Since hypertriglycemia is associated with an increased risk of cardiovascular disease and severe pancreatitis, it is very important to make a proper diagnosis of the cause of hypertriglycemia. CASE DESCRIPTION: We herein present the case of a 40-year-old male who developed severe hypertriglycemia accompanied with acute exacerbation of type 2 diabetes mellitus...
2016: SpringerPlus
Anthony Heagerty
There is now a considerable body of evidence to suggest that the fat cells that surround blood vessels (perivascular adipose tissue, PVAT) can influence profoundly arterial tone by releasing vasodilator adipokines which can act locally in a paracrine fashion. In healthy lean individuals the primary vasodilator released appears to be adiponectin and there is a complex interation between autonomic nerve firing in PVAT and the release of nitric oxide from adipocytes and an increased bioavailability of adiponectin...
September 2016: Journal of Hypertension
Zhou-Yang Jiao, Jing Wu, Chao Liu, Bing Wen, Wen-Zeng Zhao, Xin-Ling Du
Obesity is associated with chronic low‑grade inflammation, which is characterized by increased infiltration of macrophages into adipose tissue. Acylation stimulating protein (ASP) is an adipokine derived from the immune complement system, which constitutes a link between adipocytes and macrophages, and is involved in energy homeostasis and inflammation. The purpose of the present study was to preliminarily investigate in vitro, whether functional α7nAChR in adipocytes may suppress ASP‑induced inflammation and determine the possible signaling mechanism...
October 2016: Molecular Medicine Reports
Hao Yang, Jiang W Wu, Shu P Wang, Ilenia Severi, Loris Sartini, Norma Frizzell, Saverio Cinti, Gongshe Yang, Grant A Mitchell
Obesity and type 2 diabetes are associated with impaired mitochondrial function in adipose tissue. To study the effects of primary deficiency of mitochondrial energy metabolism in fat, we generated mice with adipose-specific deficiency of fumarate hydratase (FH), an integral Krebs cycle enzyme (AFHKO mice). AFHKO mice have severe ultrastructural abnormalities of mitochondria, ATP depletion in white and brown adipose tissues (WAT, BAT), low WAT mass with small adipocytes and impaired thermogenesis with large unilocular brown adipocytes...
August 23, 2016: Diabetes
Ali M Komai, Saliha Musovic, Eduard Peris, Ahmed Alrifaiy, Mickaël F El Hachmane, Marcus Johansson, Ingrid Wernstedt Asterholm, Charlotta S Olofsson
We investigated the physiological regulation of adiponectin exocytosis in health and metabolic disease by a combination of membrane capacitance patch-clamp recordings and biochemical measurements of short-term (30 min incubations) adiponectin secretion. Adrenaline or the β3 adrenergic receptor agonist CL 316,243 (CL) stimulated adiponectin exocytosis/secretion in cultured 3T3-L1 and in primary subcutaneous mouse adipocytes and the stimulation was inhibited by the Epac (Exchange Protein directly Activated by cAMP) antagonist ESI-09...
August 23, 2016: Diabetes
Åsa Jufvas, Meenu R Rajan, Cecilia Jönsson, Peter Strålfors, Maria V Turkina
The ubiquitously expressed IQ motif-containing GTPase activating protein-1 (IQGAP1) is a scaffolding protein implicated in an array of cellular functions, in particular by binding to cytoskeletal elements and signaling proteins. A role of IQGAP1 in adipocytes has not been reported. We therefore investigated the cellular IQGAP1 interactome in primary human adipocytes. Immunoprecipitation and quantitative mass spectrometry identified caveolae and caveolae-associated proteins as the major IQGAP1 interactors alongside cytoskeletal proteins...
October 1, 2016: Biochemical Journal
Chia-Lin Lee, Shou-Lun Lee, Chao-Jung Chen, Hsin-Chun Chen, Ming-Ching Kao, Chuan-Hao Liu, Jau-Yang Chen, Yen-Ting Lai, Yang-Chang Wu
Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four crude extracts, including n-hexane- (IBH), 95% MeOH- (IBM), n-BuOH- (IBB), and H₂O-soluble (IBW) fractions, were prepared by fractionation of a methanolic extract of purple I. batatas leaves. Twenty-four pure compounds 1-24 were then isolated by various chromatographic techniques and their structures identified from NMR and MS data...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Di Wu, Qian-Yun Xi, Xiao Cheng, Tao Dong, Xiao-Tong Zhu, Gang Shu, Li-Na Wang, Qing-Yan Jiang, Yong-Liang Zhang
TNF-α is a multifunctional cytokine participating in immune disorders, inflammation, and tumor development with regulatory effects on energy metabolism. Our work focused on the function of TNF-α in adipogenesis of primary porcine adipocytes. TNF-α could suppress the insulin receptor (IR) at the mRNA and protein levels. Microarray analysis of TNF-α-treated porcine adipocytes was used to screen out 29 differentially expressed microRNAs (miRNAs), 13 of which were remarkably upregulated and 16 were intensely downregulated...
August 2016: Journal of Lipid Research
Martine Duclos
BACKGROUND: Obesity and type 2 diabetes (T2D) significantly increase the risk of developing an arthritic condition. METHODS: We performed a review of literature on the pathophysiological mechanisms that underpin the relationships between obesity, T2D and osteoarthritis (OA). RESULTS: The pathophysiology of the link between obesity and OA is related to both the direct effect of excess mechanical loads being placed on the cartilage and to an adipose tissue effect...
June 2016: Annals of Physical and Rehabilitation Medicine
Ting Luo, Allison Nocon, Jessica Fry, Alex Sherban, Xianliang Rui, Bingbing Jiang, X Julia Xu, Jingyan Han, Yun Yan, Qin Yang, Qifu Li, Mengwei Zang
Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although adipose tissue fibrosis impairs adipocyte plasticity, little is known about how aberrant extracellular matrix (ECM) remodeling of WAT is initiated during the development of obesity. Here we show that treatment with the antidiabetic drug metformin inhibits excessive ECM deposition in WAT of ob/ob mice and mice with diet-induced obesity, as evidenced by decreased collagen deposition surrounding adipocytes and expression of fibrotic genes including the collagen cross-linking regulator LOX Inhibition of interstitial fibrosis by metformin is likely attributable to the activation of AMPK and the suppression of transforming growth factor-β1 (TGF-β1)/Smad3 signaling, leading to enhanced systemic insulin sensitivity...
August 2016: Diabetes
Zhi Yi Wan, Johann Shane Tian, Hayden Weng Siong Tan, Ai Lee Chow, Arthur Yi Loong Sim, Kenneth Hon Kim Ban, Yun Chau Long
UNLABELLED: Fibroblast growth factor 19 (FGF19) is an important postprandial enterokine which regulates liver metabolism and hepatocyte proliferation. However, the precise mechanism by which FGF19 regulates these cellular effects is poorly understood. Given that mechanistic target of rapamycin complex 1 (mTORC1) regulates numerous postprandial adaptations, we investigated the potential role of mTORC1 in FGF19 action. We found that FGF19 activated mTORC1 in HepG2 and HuH7 human hepatoma cells, differentiated 3T3-L1 adipocytes and mouse liver...
October 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Kosuke Okada, Katherine B LeClair, Yongzhao Zhang, Yingxia Li, Cafer Ozdemir, Tibor I Krisko, Susan J Hagen, Rebecca A Betensky, Alexander S Banks, David E Cohen
OBJECTIVE: Non-shivering thermogenesis in brown adipose tissue (BAT) plays a central role in energy homeostasis. Thioesterase superfamily member 1 (Them1), a BAT-enriched long chain fatty acyl-CoA thioesterase, is upregulated by cold and downregulated by warm ambient temperatures. Them1 (-/-) mice exhibit increased energy expenditure and resistance to diet-induced obesity and diabetes, but the mechanistic contribution of Them1 to the regulation of cold thermogenesis remains unknown. METHODS: Them1 (-/-) and Them1 (+/+) mice were subjected to continuous metabolic monitoring to quantify the effects of ambient temperatures ranging from thermoneutrality (30 °C) to cold (4 °C) on energy expenditure, core body temperature, physical activity and food intake...
May 2016: Molecular Metabolism
Wei Gao, Hao Wang, Lin Zhang, Yang Cao, Ji-Zhang Bao, Zheng-Xia Liu, Lian-Sheng Wang, Qin Yang, Xiang Lu
Insulin resistance plays a major role in the development and progression of cardiac hypertrophy and heart failure. Heart failure in turn promotes insulin resistance and increases the risk for diabetes. The vicious cycle determines significant mortality in patients with heart failure and diabetes. However, the underlying mechanisms for the vicious cycle are not fully elucidated. Here we show that circulating levels and adipose expression of retinol-binding protein 4 (RBP4), an adipokine that contributes to systemic insulin resistance, were elevated in cardiac hypertrophy induced by transverse aortic constriction and angiotensin-II (Ang-II) infusion...
June 2016: Endocrinology
Cheol Ryong Ku, Yoon Hee Cho, Zhen Yu Hong, Ha Lee, Sue Ji Lee, Seung Soo Hong, Eun Jig Lee
BACKGROUND: Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. METHODS: For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV...
June 2016: Endocrinology and Metabolism
Martin Weiszenstein, Larissa A Shimoda, Michal Koc, Ondrej Seda, Jan Polak
Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20...
August 2016: American Journal of Respiratory Cell and Molecular Biology
D I Kuzmenko, S N Udintsev, T K Klimentyeva, V Yu Serebrov
Obesity is a leading risk factor of diabetes mellitus type 2, impairments of lipid metabolism and cardiovascular diseases. Dysfunctions of the accumulating weight of the visceral fat are primarily linked to pathogenesis of systemic insulin resistance. The review considers modern views about biochemical mechanisms underlying formation of oxidative stress in adipocytes at obesity, as one of key elements of impairments of their metabolism triggering formation of systemic insulin resistance.
January 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
David P Sparling, Junjie Yu, KyeongJin Kim, Changyu Zhu, Sebastian Brachs, Andreas L Birkenfeld, Utpal B Pajvani
OBJECTIVE: As the obesity pandemic continues to expand, novel molecular targets to reduce obesity-related insulin resistance and Type 2 Diabetes (T2D) continue to be needed. We have recently shown that obesity is associated with reactivated liver Notch signaling, which, in turn, increases hepatic insulin resistance, opening up therapeutic avenues for Notch inhibitors to be repurposed for T2D. Herein, we tested the systemic effects of γ-secretase inhibitors (GSIs), which prevent endogenous Notch activation, and confirmed these effects through creation and characterization of two different adipocyte-specific Notch loss-of-function mouse models through genetic ablation of the Notch transcriptional effector Rbp-Jk (A-Rbpj) and the obligate γ-secretase component Nicastrin (A-Nicastrin)...
February 2016: Molecular Metabolism
Maximilian Michel, Patrick S Page-McCaw, Wenbiao Chen, Roger D Cone
Leptin is the primary adipostatic factor in mammals. Produced largely by adipocytes in proportion to total adipose mass, the hormone informs the brain regarding total energy stored as triglycerides in fat cells. The hormone acts on multiple circuits in the brain to regulate food intake, autonomic outflow, and endocrine function to maintain energy balance. In addition to regulating adipose mass, mammalian leptin also plays a role in the regulation of glucose homeostasis and as a gating factor in reproductive competence...
March 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
Mehmet Uzunlulu, Ozge Telci Caklili, Aytekin Oguz
Growing data show the association of metabolic syndrome (MetS) or its components with cancer development and cancer-related mortality. It is suggested that in MetS and cancer association, insulin resistance and insulin-like growth factor 1 system play a key role, especially adipokines secreted from visceral adipocytes, free fatty acids and aromatase activity contribute to this process. It is also reported that MetS has a link with colorectal, breast, endometrial, pancreas, primary liver and, although controversial, prostate cancer...
2016: Annals of Nutrition & Metabolism
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