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Preadipocyte hypoxia

Ryota Kikuchi, Takao Tsuji, Osamu Watanabe, Kazuhiro Yamaguchi, Kinya Furukawa, Hiroyuki Nakamura, Kazutetsu Aoshiba
Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia...
June 14, 2017: American Journal of Respiratory Cell and Molecular Biology
Atilla Engin
Obese subjects exhibit lower adipose tissue oxygen consumption in accordance with the lower adipose tissue blood flow. Thus, compared with lean subjects, obese subjects have 44% lower capillary density and 58% lower vascular endothelial growth factor (VEGF). The VEGF expression together with hypoxia-inducible transcription factor-1 (HIF-1) activity also requires phosphatidylinositol 3-kinase (PI3K)- and target of rapamycin (TOR)-mediated signaling. HIF-1alpha is an important signaling molecule for hypoxia to induce the inflammatory responses...
2017: Advances in Experimental Medicine and Biology
Hyerim Song, Do Young Lim, Jae In Jung, Han Jin Cho, So Young Park, Gyoo Taik Kwon, Young-Hee Kang, Ki Won Lee, Myung-Sook Choi, Jung Han Yoon Park
Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates melanoma progression in the B16F10 allograft model. In this study, we examined whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD-diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were subcutaneously injected and the primary tumor was resected 3 weeks later. OL suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD-induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2), lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1α and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2 macrophages (MΦs)...
May 9, 2017: Oncotarget
K Avila-George, K Ramos-Olivares, K Vasquez-Munoz, V Villanueva-Morales, M Reyes-Farias, P Quintero, L Garcia, D F Garcia-Diaz
Expansion of white adipose tissue induce insufficient vascularization, driving hypoxia and low-grade inflammation. Resident preadipocytes are thought to be involved. We evaluated the effects of hypoxia over preadipocytes and adipocytes, to determine which cellular type impacts the most over macrophages activation. 3T3-L1 cells were either differentiated, or maintained undifferentiated. Each group was subjected to the presence or absence of chemical hypoxia (200 μM CoCl2) for 24 h. Conditioned media were used as treatment for murine RAW264...
July 2017: Archives of Physiology and Biochemistry
Ana Patrícia Marques, Joana Rosmaninho-Salgado, Marta Estrada, Vera Cortez, Rui Jorge Nobre, Cláudia Cavadas
BACKGROUND: Hypoxia occurs within adipose tissue of obese human and mice. However, its role in adipose tissue regulation is still controversial. METHODS: We used murine preadipocyte 3T3-L1 cells and hypoxia was induced by using hypoxia mimetic agents, as CoCl2. To study adipocyte differentiation, we evaluated the adipocyte markers (PPARγ, C/EBPα and aP2), and a preadipocyte marker (pref-1) by qPCR, western blotting and immunofluorescence. Lipid accumulation was evaluated by Oil red-O assay and perilipin levels by western blotting and immunofluorescence...
March 2017: Biochimica et Biophysica Acta
Akiko Takikawa, Arshad Mahmood, Allah Nawaz, Tomonobu Kado, Keisuke Okabe, Seiji Yamamoto, Aminuddin Aminuddin, Satoko Senda, Koichi Tsuneyama, Masashi Ikutani, Yasuharu Watanabe, Yoshiko Igarashi, Yoshinori Nagai, Kiyoshi Takatsu, Keiichi Koizumi, Johji Imura, Nobuhito Goda, Masakiyo Sasahara, Michihiro Matsumoto, Kumiko Saeki, Takashi Nakagawa, Shiho Fujisaka, Isao Usui, Kazuyuki Tobe
Adipose tissue hypoxia is an important feature of pathological adipose tissue expansion. Hypoxia-inducible factor-1α (HIF-1α) in adipocytes reportedly induces oxidative stress and fibrosis, rather than neoangiogenesis via vascular endothelial growth factor (VEGF)-A. We previously reported that macrophages in crown-like structures (CLSs) are both hypoxic and inflammatory. In the current study, we examined how macrophage HIF-1α is involved in high-fat diet (HFD)-induced inflammation, neovascularization, hypoxia, and insulin resistance using mice with myeloid cell-specific HIF-1α deletion that were fed an HFD...
December 2016: Diabetes
Bimit Mahat, Étienne Chassé, Jean-François Mauger, Pascal Imbeault
BACKGROUND: Adipose tissue regulates postprandial lipid metabolism by storing dietary fat through lipoprotein lipase-mediated hydrolysis of exogenous triglycerides, and by inhibiting delivery of endogenous non-esterified fatty acid to nonadipose tissues. Animal studies show that acute hypoxia, a model of obstructive sleep apnea, reduces adipose tissue lipoprotein lipase activity and increases non-esterified fatty acid release, adversely affecting postprandial lipemia. These observations remain to be tested in humans...
2016: Journal of Translational Medicine
Christopher J Pelham, Elizabeth M Drews, Devendra K Agrawal
Vitamin D deficiency in human subjects is associated with hypertension, metabolic syndrome and related risk factors of cardiovascular diseases. Serum 25-hydroxyvitamin D levels correlate inversely with adiposity in obese and lean individuals. Bioactive vitamin D, or calcitriol, exerts anti-inflammatory effects on adipocytes, preadipocytes and macrophages in vitro. We tested the hypothesis that vitamin D deficiency alters the phenotype of perivascular adipose tissue (PVAT) leading to impaired function in resistance artery...
September 2016: Journal of Molecular and Cellular Cardiology
Jung Eun Jang, Myoung Seok Ko, Ji-Young Yun, Mi-Ok Kim, Jin Hee Kim, Hye Sun Park, Ah-Ram Kim, Hyuk-Joong Kim, Bum Joong Kim, Young Eun Ahn, Jin Sun Oh, Woo Je Lee, Robert A Harris, Eun Hee Koh, Ki-Up Lee
Fibrosis of adipose tissue induces ectopic fat accumulation and insulin resistance by inhibiting adipose tissue expandability. Mechanisms responsible for the induction of adipose tissue fibrosis may provide therapeutic targets but are poorly understood. In this study, high-fat diet (HFD)-fed wild-type (WT) and iNOS(-/-) mice were used to examine the relationship between nitric oxide (NO) produced by macrophages and adipose tissue fibrosis. In contrast to WT mice, iNOS(-/-) mice fed an HFD were protected from infiltration of proinflammatory macrophages and adipose tissue fibrosis...
September 2016: Diabetes
Martin Weiszenstein, Nela Pavlikova, Moustafa Elkalaf, Petr Halada, Ondrej Seda, Jan Trnka, Jan Kovar, Jan Polak
Pericellular oxygen concentration represents an important factor in the regulation of cell functions, including cell differentiation, growth and mitochondrial energy metabolism. Hypoxia in adipose tissue has been associated with altered adipokine secretion profile and suggested as a possible factor in the development of type 2 diabetes. In vitro experiments provide an indispensable tool in metabolic research, however, physical laws of gas diffusion make prolonged exposure of adherent cells to desired pericellular O2 concentrations questionable...
2016: PloS One
Qi Zhu, Lin Wang, Yue Zuo, Chang Shan, Jing Yu, Lige Song, Keqin Zhang
This study aimed to investigate the effect of adipocytes on osteoblastic bone formation in vitro. The differentiated and undifferentiated 3T3-L1 cells were co-cultured with primary calvarial osteoblasts. At 48 h, proliferated osteoblasts decreased significantly after co-culture with differentiated preadipocytes as compared to those co-cultured with undifferentiated preadipocytes; at 7 days, the expressions of bone formation-related genes decreased in osteoblasts co-cultured with differentiated preadipocytes; at 14 days, osteoblasts mineralization also decreased significantly after co-culture with differentiated preadipocytes...
2015: American Journal of Translational Research
Helena H Chowdhury, Jelena Velebit, Nataša Radić, Vito Frančič, Marko Kreft, Robert Zorec
Dipeptidyl peptidase 4 (DPP4), a transmembrane protein, has been identified in human adipose tissue and is considered to be associated with obesity-related type 2 diabetes. Since adipose tissue is relatively hypoxic in obese participants, we investigated the expression of DPP4 in human preadipocytes (hPA) and adipocytes in hypoxia, during differentiation and upon insulin stimulation. The results show that DPP4 is abundantly expressed in hPA but very sparsely in adipocytes. During differentiation in vitro, the expression of DPP4 in hPA is reduced on the addition of differentiation medium, indicating that this protein can be hPA marker...
2016: Journal of Diabetes Research
H Lu, Z Gao, Z Zhao, J Weng, J Ye
OBJECTIVES: To investigate the impact of transient (2-4 h) hypoxia on metabolic reprogramming of adipocytes. METHODS: The impact of transient hypoxia on metabolic reprogramming was investigated in 3T3-L1 cells before and after differentiation. Glucose uptake, fatty acid oxidation, lipolysis and mitochondria were examined to determine the hypoxia effects. Preadipocytes were exposed to transient hypoxia (4 h day(-1)) in the course of differentiation. Insulin sensitivity and triglyceride (TG) accumulation was examined in the cells at the end of differentiation to determine the reprogramming effects...
January 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Christa Buechler, Sabrina Krautbauer, Kristina Eisinger
The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. Thereby adipose tissue growth is limited and excess triglycerides are stored in ectopic tissues...
May 15, 2015: World Journal of Diabetes
Jan-Bernd Funcke, Verena Zoller, Muad Abd El Hay, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky
Upon obesity, adipose tissue is excessively expanded and characterized by pathologic processes like hypoxia, fibrosis, and inflammation. Death ligands belonging to the TNF superfamily such as TNF-α are important contributors to these derangements and exert a pronounced influence on the metabolic and cellular homeostasis of adipose tissue. Here, we sought to identify the effect of the death ligand TNF-related apoptosis-inducing ligand (TRAIL) on the adipose tissue precursor cell pool and therefore investigated its influence on preadipocyte proliferation...
July 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Harunosuke Kato, Jun Araki, Kentaro Doi, Shinichiro Kuno, Kahori Kinoshita, Kazuhide Mineda, Koji Kanayama, Kotaro Yoshimura
BACKGROUND: Fat grafting is a promising modality for soft-tissue augmentation/reconstruction. However, grafted fat tissue is not initially perfused and relies on plasmatic diffusion from the recipient bed until revascularization occurs. The authors evaluated the therapeutic effects of normobaric hyperoxygenation for enhancing fat graft retention. METHODS: Aspirated human fat tissue was cultured under tissue hypoxia (1% oxygen), normoxia (6%), and hyperoxia (20%) levels, and evaluated for adipocyte viability...
November 2014: Plastic and Reconstructive Surgery
Paul Trayhurn
Hypoxia develops in white adipose tissue in obese mice, resulting in changes in adipocyte function that may underpin the dysregulation that leads to obesity-associated disorders. Whether hypoxia occurs in adipose tissue in human obesity is unclear, with recent studies contradicting earlier reports that this was the case. Adipocytes, both murine and human, exhibit extensive functional changes in culture in response to hypoxia, which alters the expression of up to 1,300 genes. These include genes encoding key adipokines such as leptin, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2), which are upregulated, and adiponectin, which is downregulated...
2014: Annual Review of Nutrition
Soichi Sano, Yasukatsu Izumi, Takehiro Yamaguchi, Takanori Yamazaki, Masako Tanaka, Masayuki Shiota, Mayuko Osada-Oka, Yasuhiro Nakamura, Min Wei, Hideki Wanibuchi, Hiroshi Iwao, Minoru Yoshiyama
Hypoxia occurs within adipose tissues as a result of adipocyte hypertrophy and is associated with adipocyte dysfunction in obesity. Here, we examined whether hypoxia affects the characteristics of adipocyte-derived exosomes. Exosomes are nanovesicles secreted from most cell types as an information carrier between donor and recipient cells, containing a variety of proteins as well as genetic materials. Cultured differentiated 3T3-L1 adipocytes were exposed to hypoxic conditions and the protein content of the exosomes produced from these cells was compared by quantitative proteomic analysis...
March 7, 2014: Biochemical and Biophysical Research Communications
Lingni Yin, Wenwei Cai, Jing Sheng, Yun Sun
Human adipose tissues secret a lot of cytokines involved in physiological and pathological activities. Inflammation around blood vessels is positively related to the severity of atherosclerosis. This study was to investigate the impact of adipokine SePP1 on vascular fibroblasts (VF) under a hypoxia condition might provide new evidence and methods for treatment of atherosclerosis. The mRNA and protein expression of IL-6, MCP-1 and SePP1 were detected in preadipocytes under normoxic (21% O2) and hyperoxic (4% O2) conditions, and the impact of IL-6, MCP-1 and SePP1 on VF was investigated...
2014: International Journal of Clinical and Experimental Medicine
Heather M White, Anthony J Acton, Malgorzata M Kamocka, Robert V Considine
In this study, we used lentiviral-delivered shRNA to generate a clonal line of 3T3-F442A preadipocytes with stable silencing of hepatocyte growth factor (HGF) expression and examined the long-term consequence of this modification on fat pad development. HGF mRNA expression was reduced 94%, and HGF secretion 79% (P < 0.01), compared with preadipocytes treated with nontargeting shRNA. Fat pads derived from HGF knockdown preadipocytes were significantly smaller (P < 0.01) than control pads beginning at 3 days postinjection (0...
January 15, 2014: American Journal of Physiology. Endocrinology and Metabolism
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