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primary adipocyte diabetes

Leryn J Reynolds, Brett J Dickens, Benjamin B Green, Carmen J Marsit, Kevin J Pearson
Numerous studies have examined how both negative and positive maternal exposures (environmental contaminants, nutrition, exercise, etc.) impact offspring risk for age-associated diseases such as obesity, type 2 diabetes, hypertension, and others. The purpose of this study was to introduce the foreskin as a novel model to examine developmental programming in human neonates, particularly in regard to adipogenesis and insulin receptor signaling, major contributors to age-associated diseases such as obesity and diabetes...
December 27, 2016: Experimental Gerontology
Rasmus Magnusson, Mika Gustafsson, Gunnar Cedersund, Peter Strålfors, Elin Nyman
The molecular mechanisms of insulin resistance in Type 2 diabetes have been extensively studied in primary human adipocytes, and mathematical modelling has clarified the central role of attenuation of mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activity in the diabetic state. Attenuation of mTORC1 in diabetes quells insulin-signalling network-wide, except for the mTOR in complex 2 (mTORC2)-catalysed phosphorylation of protein kinase B (PKB) at Ser(473) (PKB-S473P), which is increased. This unique increase could potentially be explained by feedback and interbranch cross-talk signals...
February 28, 2017: Bioscience Reports
Jesper S Hansen, Christian Krintel, Malin Hernebring, Tatu J K Haataja, Sofia de Marè, Sebastian Wasserstrom, Urszula Kosinska-Eriksson, Madelene Palmgren, Cecilia Holm, Karin G Stenkula, Helena A Jones, Karin Lindkvist-Petersson
Accumulating evidence suggests that dysregulated glycerol metabolism contributes to the pathophysiology of obesity and type 2 diabetes. Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Here, we propose a molecular mechanism where the AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation...
December 2016: Metabolism: Clinical and Experimental
Hiroshi Kaji
Adipose tissue has recently been reevaluated as an endocrine organ, and adipose-tissue-derived endocrine factors are termed adipokines. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of PAs, which convert plasminogen into plasmin, a critical protease involved in fibrinolysis. PAI-1 induces fibrinogenesis by suppressing intravascular and tissue fibrinolysis. Moreover, PAI-1 exerts various cellular effects independently of fibrinolysis. Although PAI-1 is expressed in various tissues, its expression is regulated by numerous growth factors, cytokines, and hormones in a paracrine and endocrine manner...
September 15, 2016: Comprehensive Physiology
Christian Carpéné, Francisco Les, Mounia Hasnaoui, Simon Biron, Picard Marceau, Denis Richard, Jean Galitzky, Denis R Joanisse, Pascale Mauriège
Semicarbazide-sensitive amine oxidase (SSAO), identical to primary amine oxidase or vascular adhesion protein-1, is a membrane enzyme that generates hydrogen peroxide. SSAO is highly expressed at the adipocyte surface, and its plasma levels increase with type 2 diabetes. Since visceral adipose tissue (AT) is more tightly associated with obesity complications than subcutaneous (SC) abdominal fat, we compared SSAO activity in plasma and 4 distinct AT locations in 48 severely obese women (body mass index (BMI), averaging 54 ± 11 kg/m(2)), with or without a dysmetabolic profile...
October 21, 2016: Journal of Physiology and Biochemistry
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
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 adipose tissue (WAT) and brown adipose tissue, low WAT mass with small adipocytes, and impaired thermogenesis with large unilocular brown adipocytes...
November 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. Epinephrine or the β3-adrenergic receptor (AR) 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...
November 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...
June 8, 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
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