Lieb David C, Brotman Joshua J, Hatcher Margaret A, Aye Myo S, Cole Banumathi K, Haynes Bronson A, Wohlgemuth Stephen D, Fontana Mark A, Beydoun Hind, Nadler Jerry L, Dobrian Anca D
Departments of Internal Medicine (D.C.L., B.K.C., J.L.N.) and Physiological Sciences (J.J.B., M.A.H., M.S.A., B.A.H., A.D.D.) and Graduate Program in Public Health (H.B.), Eastern Virginia Medical School, Norfolk, Virginia 23507; and Sentara Metabolic and Weight Loss Surgery Center (S.D.W., M.A.F.), Sentara Medical Group, Norfolk, Virginia 23502.
J Clin Endocrinol Metab. 2014 Sep;99(9):E1713-20. doi: 10.1210/jc.2013-4461. Epub 2014 Jun 23.
Visceral adipose tissue (VAT) is a key contributor to chronic inflammation in obesity. The 12/15-lipoxygenase pathway (ALOX) is present in adipose tissue (AT) and leads to inflammatory cascades that are causal for the onset of insulin resistance in rodent models of obesity.
The pathophysiology of the ALOX 12/15 pathway in human AT is unknown. We characterized the ALOX pathway in different AT depots in obese humans with or without type 2 diabetes (T2D).
This study includes a cross-sectional cohort of 46 morbidly obese (body mass index >39 kg/m(2)) nondiabetic (n = 25) and T2D (n = 21) subjects.
This study was conducted at Eastern Virginia Medical School (Norfolk, Virginia) in collaboration with Sentara Metabolic and Weight Loss Surgery Center (Sentara Medical Group, Norfolk, Virginia).
Twenty-five obese (body mass index 44.8 ± 4.4 kg/m(2)) nondiabetic (hemoglobin A1c 5.83% ± 0.27%) and 21 obese (43.4 ± 4.1 kg/m(2)) and T2D (hemoglobin A1c 7.66% ± 1.22%) subjects were included in the study. The subjects were age matched and both groups had a bias toward female gender.
Expression of ALOX isoforms along with fatty acid substrates and downstream lipid metabolites were measured. Correlations with depot-specific inflammatory markers were also established.
ALOX 12 expression and its metabolite 12(S)-hydroxyeicosatetraenoic acid were significantly increased in the VAT of T2D subjects. ALOX 15A was exclusively expressed in VAT in both groups. ALOX 12 expression positively correlated with expression of inflammatory genes IL-6, IL-12a, CXCL10, and lipocalin-2.
ALOX 12 may have a critical role in regulation of inflammation in VAT in obesity and T2D. Selective ALOX 12 inhibitors may constitute a new approach to limit AT inflammation in human obesity.
内脏脂肪组织（VAT）是肥胖中慢性炎症的关键促成因素。12/15-脂氧合酶途径（ALOX）存在于脂肪组织（AT）中，并导致炎症级联反应，这在肥胖啮齿动物模型中是胰岛素抵抗发生的原因。
人类AT中ALOX 12/15途径的病理生理学尚不清楚。我们对有或无2型糖尿病（T2D）的肥胖人类不同AT库中的ALOX途径进行了表征。
本研究包括一个横断面队列，共46名病态肥胖（体重指数>39 kg/m²）的非糖尿病（n = 25）和T2D（n = 21）受试者。
本研究在东弗吉尼亚医学院（弗吉尼亚州诺福克）与Sentara代谢与减肥手术中心（Sentara医疗集团，弗吉尼亚州诺福克）合作进行。
25名肥胖（体重指数44.8±4.4 kg/m²）非糖尿病（糖化血红蛋白5.83%±0.27%）和21名肥胖（43.4±4.1 kg/m²）且患有T2D（糖化血红蛋白7.66%±1.22%）的受试者被纳入研究。受试者年龄匹配，两组均偏向女性。
测量ALOX亚型以及脂肪酸底物和下游脂质代谢物的表达。还建立了与库特异性炎症标志物的相关性。
T2D受试者的VAT中ALOX 12表达及其代谢物12(S)-羟基二十碳四烯酸显著增加。两组中ALOX 15A仅在VAT中表达。ALOX 12表达与炎症基因IL-6、IL-12a、CXCL10和lipocalin-2的表达呈正相关。
ALOX 12可能在肥胖和T2D中VAT炎症的调节中起关键作用。选择性ALOX 12抑制剂可能构成一种限制人类肥胖中AT炎症的新方法。
