Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.
Interleukin-6 induces impairment in human subcutaneous adipogenesis in obesity-associated insulin resistance.
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DOI：
10.1007/s00125-016-4031-3
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发表时间：
2016-11
期刊：
影响因子：
8.2
通讯作者：
Elrayess MA
中科院分区：
文献类型：
--
作者：
Almuraikhy S;Kafienah W;Bashah M;Diboun I;Jaganjac M;Al-Khelaifi F;Abdesselem H;Mazloum NA;Alsayrafi M;Mohamed-Ali V;Elrayess MA
一部分肥胖个体仍对胰岛素敏感，其机制尚不清楚。维持正常皮下（SC）脂肪形成的假设，至少部分解释了这种保护性表型，以及它是否可以被慢性暴露于IL-6所废除。从接受减肥手术的胰岛素敏感（IS）和胰岛素抵抗（IR）个体中收集脂肪组织活检。测定脂肪细胞大小、基质血管组分（SVF）衍生细胞的前脂肪细胞比例、成脂能力和分离前脂肪细胞的基因表达谱，以及局部体外IL-6分泌情况。进一步评估外源性IL-6应用对脂肪生成能力的影响。尽管同样肥胖，但与同龄IS患者相比，IR患者的血浆瘦素和脂联素水平明显较低，IL-6水平较高。IR个体的全身IL-6升高与脂肪组织来源的SVF细胞增生有关，尽管肥大的脂肪细胞频率更高。来自这些组织的SC前脂肪细胞表现出较低的成脂能力，并伴有PPARG γ（也称为PPARG）和CEBPα（也称为CEBPA）的下调和GATA3表达的上调。IR个体的脂肪生成受损与IL-6脂肪分泌增加进一步相关。用IL-6治疗is源性SC前脂肪细胞，使其成脂能力降至IR组的水平。肥胖相关的胰岛素抵抗以SC脂肪生成受损为特征，至少在一部分个体中，这是由局部IL-6水平升高介导的。了解IR个体脂肪生成能力降低的分子机制有助于针对胰岛素抵抗和2型糖尿病高危人群制定适当的治疗策略。
A subset of obese individuals remains insulin sensitive by mechanisms as yet unclear. The hypothesis that maintenance of normal subcutaneous (SC) adipogenesis accounts, at least partially, for this protective phenotype and whether it can be abrogated by chronic exposure to IL-6 was investigated. Adipose tissue biopsies were collected from insulin-sensitive (IS) and insulin-resistant (IR) individuals undergoing weight-reduction surgery. Adipocyte size, pre-adipocyte proportion of stromal vascular fraction (SVF)-derived cells, adipogenic capacity and gene expression profiles of isolated pre-adipocytes were determined, along with local in vitro IL-6 secretion. Adipogenic capacity was further assessed in response to exogenous IL-6 application. Despite being equally obese, IR individuals had significantly lower plasma leptin and adiponectin levels and higher IL-6 levels compared with age-matched IS counterparts. Elevated systemic IL-6 in IR individuals was associated with hyperplasia of adipose tissue-derived SVF cells, despite higher frequency of hypertrophied adipocytes. SC pre-adipocytes from these tissues exhibited lower adipogenic capacity accompanied by downregulation of PPARγ (also known as PPARG) and CEBPα (also known as CEBPA) and upregulation of GATA3 expression. Impaired adipogenesis in IR individuals was further associated with increased adipose secretion of IL-6. Treatment of IS-derived SC pre-adipocytes with IL-6 reduced their adipogenic capacity to levels of the IR group. Obesity-associated insulin resistance is marked by impaired SC adipogenesis, mediated, at least in a subset of individuals, by elevated local levels of IL-6. Understanding the molecular mechanisms underlying reduced adipogenic capacity in IR individuals could help target appropriate therapeutic strategies aimed at those at greatest risk of insulin resistance and type 2 diabetes mellitus.
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DOI：
10.1152/ajpendo.90511.2008
发表时间：
2009-06
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
Madani R;Karastergiou K;Ogston NC;Miheisi N;Bhome R;Haloob N;Tan GD;Karpe F;Malone-Lee J;Hashemi M;Jahangiri M;Mohamed-Ali V
通讯作者：
Mohamed-Ali V
影响因子：
7.7
作者：
Gustafson B;Hammarstedt A;Hedjazifar S;Smith U
通讯作者：
Smith U
影响因子：
29
作者：
Kraakman, Michael J.;Kammoun, Helene L.;Febbraio, Mark A.
通讯作者：
Febbraio, Mark A.
影响因子：
3.8
作者：
Flower, L;Gray, R;Mohamed-Ali, V
通讯作者：
Mohamed-Ali, V
影响因子：
14.9
作者：
Foka, P;Irvine, SA;Ramji, DP
通讯作者：
Ramji, DP