Subcutaneous Adipose Tissue Macrophage Infiltration Is Associated With Hepatic and Visceral Fat Deposition, Hyperinsulinemia, and Stimulation of NF-κB Stress Pathway

被引:119
作者
Le, Kim-Anne [1 ]
Mahurkar, Swapna [1 ]
Alderete, Tanya L. [1 ]
Hasson, Rebecca E. [1 ]
Adam, Tanja C. [1 ]
Kim, Joon Sung [1 ,2 ]
Beale, Elizabeth [3 ]
Xie, Chen [4 ]
Greenberg, Andrew S. [4 ]
Allayee, Hooman [1 ]
Goran, Michael I. [1 ]
机构
[1] Univ So Calif, Dept Prevent Med, Childhood Obes Res Ctr, Los Angeles, CA 90089 USA
[2] Univ Ulsan, Coll Med, Ulsan Univ Hosp, Dept Pediat, Ulsan 680749, South Korea
[3] Univ So Calif, Keck Sch Med, Dept Internal Med, Div Endocrinol & Diabet, Los Angeles, CA 90033 USA
[4] Tufts Univ, Sch Med, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA
基金
瑞士国家科学基金会; 美国国家卫生研究院;
关键词
CIRCULATING MONONUCLEAR-CELLS; INSULIN-RESISTANCE; OBESE SUBJECTS; NONALCOHOLIC STEATOHEPATITIS; INFLAMMATION; MICE; ACTIVATION; EXPRESSION; LIVER; MATRIX-METALLOPROTEINASE-9;
D O I
10.2337/db10-1263
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-To examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), beta-cell function, and SAT gene expression. RESEARCH DESIGN AND METHODS-SAT biopsies were obtained from 36 obese young adults (20 Hispanics, 16 African Americans) to measure crown-like structures (CLS), reflecting SAT inflammation. SAT, VAT, and HFF were measured by magnetic resonance imaging, and SI and beta-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. RESULTS-Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CIS had greater VAT (3.7 +/- 1.3 vs. 2.6 +/- 1.6 L; P = 0.04), HFF (9.9 +/- 7.3 vs. 5.8 +/- 4.4%; P = 0.03), tumor necrosis factor-alpha (20.8 +/- 4.8 vs. 16.2 +/- 5.8 pg/mL; P = 0.01), fasting insulin (20.9 +/- 10.6 vs. 9.7 +/- 6.6 mU/mL; P < 0.001) and glucose (94.4 +/- 9.3 vs. 86.8 +/- 5.3 mg/dL; P = 0.005), and lower DI (1,559 +/- 984 vs. 2,024 +/- 829 x 10(-4) min(-1); P = 0.03). Individuals with CLS in SAT exhibited upregulation of matrix metalloproteinase-9 and monocyte antigen CD14 genes, as well as several other genes belonging to the nuclear factor-kappa B (NF-kappa B) stress pathway. CONCLUSIONS-Adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered beta-cell function, independent of total adiposity. Several genes belonging to the NF-kappa B stress pathway were upregulated, suggesting stimulation of proinflammatory mediators. Diabetes 60:2802-2809, 2011
引用
收藏
页码:2802 / 2809
页数:8
相关论文
共 37 条
[31]   Identification and characterization of metabolically benign obesity in humans [J].
Stefan, Norbert ;
Kantartzis, Konstantinos ;
Machann, Juergen ;
Schick, Fritz ;
Thamer, Claus ;
Rittig, Kilian ;
Balletshofer, Bernd ;
Machicao, Fausto ;
Fritsche, Andreas ;
Haering, Hans-Ulrich .
ARCHIVES OF INTERNAL MEDICINE, 2008, 168 (15) :1609-1616
[32]   Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation [J].
Tanti, Jean-Francois ;
Jager, Jennifer .
CURRENT OPINION IN PHARMACOLOGY, 2009, 9 (06) :753-762
[33]   Subcutaneous adipocyte size and body fat distribution [J].
Tchoukalova, Yourka D. ;
Koutsari, Christina ;
Karpyak, Maksym V. ;
Votruba, Susanne B. ;
Wendland, Eliana ;
Jensen, Michael D. .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 2008, 87 (01) :56-63
[34]   Matrix Metalloproteinase-9 Is Increased in Obese Subjects and Decreases in Response to Pioglitazone [J].
Unal, Resat ;
Yao-Borengasser, Aiwei ;
Varma, Vijayalakshmi ;
Rasouli, Neda ;
Labbate, Craig ;
Kern, Philip A. ;
Ranganathan, Gouri .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2010, 95 (06) :2993-3001
[35]   Obesity is associated with macrophage accumulation in adipose tissue [J].
Weisberg, SP ;
McCann, D ;
Desai, M ;
Rosenbaum, M ;
Leibel, RL ;
Ferrante, AW .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (12) :1796-1808
[36]   Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity [J].
Wentworth, John M. ;
Naselli, Gaetano ;
Brovvn, Wendy A. ;
Doyle, Lisa ;
Phipson, Belinda ;
Smyth, Gordon K. ;
Wabitsch, Martin ;
O'Brien, Paul E. ;
Harrison, Leonard C. .
DIABETES, 2010, 59 (07) :1648-1656
[37]   Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance [J].
Xu, HY ;
Barnes, GT ;
Yang, Q ;
Tan, Q ;
Yang, DS ;
Chou, CJ ;
Sole, J ;
Nichols, A ;
Ross, JS ;
Tartaglia, LA ;
Chen, H .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (12) :1821-1830