Research ArticleInvolvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes
Section snippets
Background
Traditionally, adipocytes and adipose tissue were primarily considered as fat depots and calory preservers. More recently, they are recognized as actively metabolic endocrine cells and organs that synthesize, store, and secrete adipokines, free fatty acids and steroid hormones [1], [2], [3]. Especially, visceral obesity is related with an incremental risk for insulin resistance and cardiovascular disease [1], [2], [4], [5], and its perivascular adipose tissue (PVAT) and perivascular adipocytes
Materials
The Rattus norvegicus rat MEOX2 plasmid was kind gift of Dr. Kenneth Walsh (St. Elizabeth׳s Medical Center, Boston, MA) and Dr. Bert Vogelstein (The Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, USA) [19]. pAdxsi was obtained from Nosai Genome Research Center Co., Ltd. (Beijing, China). All restriction enzymes were purchased from New England Biolabs (Beverly, MA, USA). Cell culture reagents were obtained from GibcoBRL (Life Technologies, Grand Island, NY).
PVAC dedifferentiation and differentiation
Morphological changes of PVACs in the ceiling culture are shown in Fig. 1. When lipid-filled mature cells (Fig. 1A) isolated from PVAT were applied into culture flasks filled completely with media, the cells got attached to upper surface of flasks and extend cytoplasm after 1 week of culture (Fig. 1B). The adhered unilocular cells flattened and lost a round contour and the dominant lipid droplets were broken into several smaller parts to exhibit a multi-ocular outlook. Approximately 70% of the
Discussion
Our investigations identify a unique role for IGF-1 mediated PI3K/Akt1/2 and ERK1/2 signaling pathways in regulating PVAC proliferation and adipogenesis. Thus this study may provide new insights into an understanding of the pro-growth and anti-apoptosis role of IGF-1 affecting PVAC functions. IGF-1 is a critical regulator of adipose tissue through its regulation of proliferation and adipogenesis by activating two downstream pathways, ERK of the MAPK family and PI3K, in vivo and in vitro [10],
Disclosures
None.
Acknowledgments
This study was supported by Grants from Shandong Provincial Natural Science Foundation (No. 2009ZRB019BS) and the National Natural Science Foundation of China (No. 81170274).
References (39)
- et al.
Crosstalk between perivascular adipose tissue and blood vessels
Curr. Opin. Pharmacol.
(2010) - et al.
NEO study group. Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study
Atherosclerosis
(2013) - et al.
“Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease
Lancet
(2005) - et al.
Paracrine role for periadventitial adipose tissue in the regulation of arterial tone
Trends Pharmacol. Sci.
(2004) - et al.
Differential signaling by adaptor molecules LRP1 and ShcA regulates adipogenesis by the insulin-like growth factor-1 receptor
J. Biol. Chem.
(2011) - et al.
Gax gene transfer inhibits vascular remodeling induced by adventitial inflammation in rabbits
Atherosclerosis
(2010) - et al.
Endothelial differentiation in multipotent cells derived from mouse and human white mature adipocytes
J. Mol. Cell. Cardiol.
(2012) - et al.
Effects of orexin A on proliferation, survival, apoptosis and differentiation of 3T3-L1 preadipocytes into mature adipocytes
FEBS Lett.
(2012) - et al.
Differential function of Akt1 and Akt2 in human adipocytes
Mol. Cell. Endocrinol.
(2012) - et al.
Gene therapy for restenosis: biological solution to a biological problem
J. Mol. Cell. Cardiol.
(2007)
Inhibition of endothelial cell activation by the homeobox gene Gax
J. Surg. Res.
The homeobox gene GAX activates p21WAF1/CIP1 expression in vascular endothelial cells through direct interaction with upstream AT-rich sequences
J. Biol. Chem.
Adipocytes produce aldosterone through calcineurin- dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction
Hypertension
Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding
Circ. Res.
Human coronary artery perivascular adipocytes overexpress genes responsible for regulating vascular morphology, inflammation, and hemostasis
Physiol. Genomics
Angiogenesis in an in vivo model of adipose tissue development
FASEB J.
Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis
Circ. Res.
IGF-I activation of the AKT pathway is impaired in visceral but not subcutaneous preadipocytes from obese subjects
Endocrinology
IGF-1 and atherothrombosis: relevance to pathophysiology and therapy
Clin. Sci. (Lond)
Cited by (23)
Parboiled rice extracts ameliorate oleic acid-induced steatosis of HepG2 cell and its molecular mechanism
2023, Journal of Functional FoodsDevelopment of precocious puberty in children: Surmised medicinal plant treatment
2022, Biomedicine and PharmacotherapyCitation Excerpt :E2 combines with ESR1 to form a hormone-receptor complex and thereby activates the estrogen signalling pathway. It has been reported that the phosphatase-binding function of Akt is required for IGF1 and PI3K to mediate adipocyte differentiation and that IGF1 is an essential mediator of preadipocyte survival, proliferation, and differentiation [156]. PI3K is a specific signaling pathway for adipocyte bioactivity, and inhibition of PI3K impairs preadipocyte differentiation [157].
Mesenchyme homeobox 2 has a cancer-inhibiting function in breast carcinoma via affection of the PI3K/AKT/mTOR and ERK1/2 pathways
2022, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Importantly, our work reported a vital role of MEOX2 in regulating the PI3K/AKT/mTOR pathway in breast carcinoma. The up-regulation of MEOX2 decreased the activation of PI3K and AKT adipocytes following the stimulation of insulin-like growth factor 1 [31]. The overexpression of MEOX2 weakens chemerin-induced preadipocyte proliferation, adipogenesis and angiogenesis by blocking the activation of AKT and mTOR [32].
A SNP in the 3′UTR of the porcine IGF-1 gene interacts with miR-new14 to affect IGF-1 expression, proliferation and apoptosis of PK-15 cells
2020, Domestic Animal EndocrinologyCitation Excerpt :Research has suggested that IGF-1, a circulating hormone and tissue growth factor, partly induces growth of the kidney [6,7]. At the same time, IGF-1 plays an irreplaceable role in normal brain development, neuronal growth, and cellular proliferation and differentiation [8,9]. Moreover, IGF-1 is known to be involved in the AKT and ERK signaling pathways [9,10].
Role of androgen receptor on cyclic mechanical stretch-regulated proliferation of C2C12 myoblasts and its upstream signals: IGF-1-mediated PI3K/Akt and MAPKs pathways
2017, Molecular and Cellular EndocrinologyCitation Excerpt :In cyclic mechanical stretch, there is accumulating evidence that cyclic mechanical stretch promoted the proliferation of several cells by increasing secretion of IGF-1 and activating IGF-1/Akt pathway, including cardiac fibroblasts (Honsho et al., 2009), vascular smooth muscle cells (J. Song et al., 2012) and bladder smooth muscle cells (Tian et al., 2013). Cyclic mechanical stretch induced vascular remodeling of vascular smooth muscle cells by activating Akt signaling (X. Liu et al., 2015; Seo et al., 2013). However, in skeletal muscle cells, the study about mechanical stretch on IGF-1/Akt/mTOR pathway was rare, and the only one report was that 15% of stretch activated mTOR of C2C12 cells to increase protein synthesis rather than proliferation (Nakai et al., 2015).
Role of developmental transcription factors in white, brown and beige adipose tissues
2015, Biochimica et Biophysica Acta - Molecular and Cell Biology of LipidsCitation Excerpt :MEOX2 encodes the protein MOX2 which regulates mesodermal patterning [157] and is essential for normal vertebrate limb myogenesis [158]. In perivascular adipocytes MEOX2 has been shown to counteract the stimulatory effects of IGF1 on adipocyte proliferation and differentiation [159]. MEOX2 has also been reported to exert anti-angiogenic effects in endothelial cells [160] and overexpression of MEOX2 induces premature fibroblast senescence [161].