کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8292414 | 1536727 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Neuregulin-4 is an angiogenic factor that is critically involved in the maintenance of adipose tissue vasculature
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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![عکس صفحه اول مقاله: Neuregulin-4 is an angiogenic factor that is critically involved in the maintenance of adipose tissue vasculature Neuregulin-4 is an angiogenic factor that is critically involved in the maintenance of adipose tissue vasculature](/preview/png/8292414.png)
چکیده انگلیسی
Adipose tissue (AT) contains well-developed vascular networks. Pathological AT expansion often accompany the reduction in AT blood vessels, which further exacerbates adipocyte dysfunction due to hypoxia; however, it remains unclear whether AT vascular rarefaction is simply secondary to adipocyte hypertrophy, or if there is an actively regulated pathway that mediates impaired AT angiogenesis in obesity. We searched for growth factors whose expression in AT is down-regulated in obesity; accordingly, we identified neuregulin-4 (Nrg4), a member of the EGF family of proteins. Nrg4 is highly and preferentially expressed in healthy adipocytes, while its expression was substantially reduced in obesity. Nrg4 activated endothelial angiogenic functions and angiogenesis both in vitro and in vivo. Genetic loss of Nrg4 caused reduction in brown and white AT blood vessels, and induced overweight even while consuming normal chow. Conditional knockout of Nrg4 in brown adipocytes caused blood vessel reduction in brown but not in white AT, and was sufficient to induce obese phenotype. Our data demonstrated that Nrg4 plays a critical role in maintaining AT vasculature and its metabolic functions. Considering the substantial reduction of Nrg4 in obesity, disruption of Nrg4-mediated angiogenesis could be an active mechanism for the obesity-associated vascular rarefaction in AT, and thus Nrg4 is an attracting pharmacotherapeutic target in the prevention and/or treatment of obesity-related metabolic disorders.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 503, Issue 1, 3 September 2018, Pages 378-384
Journal: Biochemical and Biophysical Research Communications - Volume 503, Issue 1, 3 September 2018, Pages 378-384
نویسندگان
Dhite Bayu Nugroho, Koji Ikeda, Agian Jeffilano Barinda, Donytra Arby Wardhana, Keiko Yagi, Keishi Miyata, Yuichi Oike, Ken-ichi Hirata, Noriaki Emoto,